Exercise for preventing and treating osteoporosis in postmenopausal women (Review) Howe TE, Shea B, Dawson LJ, Downie F, Murray A, Ross C, Harbour RT, Caldwell LM, Creed G

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2011, Issue 7 http://www.thecochranelibrary.com

Exercise for preventing and treating osteoporosis in postmenopausal women (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

TABLE OF CONTENTS

HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . . . . . . . . . . . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.1. Comparison 1 Any exercise versus control, Outcome 1 Total number of fractures. . . . . . . . . Analysis 1.2. Comparison 1 Any exercise versus control, Outcome 2 Bone mineral density % change: spine. . . . Analysis 1.3. Comparison 1 Any exercise versus control, Outcome 3 Bone mineral density % change: femoral neck. . Analysis 1.4. Comparison 1 Any exercise versus control, Outcome 4 Bone mineral density % change: Ward’s triangle. Analysis 1.5. Comparison 1 Any exercise versus control, Outcome 5 Bone mineral density % change: hip. . . . . Analysis 1.6. Comparison 1 Any exercise versus control, Outcome 6 Bone mineral density % change: trochanter. . . Analysis 1.7. Comparison 1 Any exercise versus control, Outcome 7 Bone mineral content % change: spine. . . . Analysis 1.8. Comparison 1 Any exercise versus control, Outcome 8 Bone mineral content % change: femoral neck. . Analysis 2.1. Comparison 2 Static weight bearing exercise versus control, Outcome 1 Bone mineral density % change: hip. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.1. Comparison 3 Dynamic weight bearing exercise low force versus control, Outcome 1 Bone mineral density % change: spine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.2. Comparison 3 Dynamic weight bearing exercise low force versus control, Outcome 2 Bone mineral density % change: femoral neck. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.3. Comparison 3 Dynamic weight bearing exercise low force versus control, Outcome 3 Bone mineral density % change: trochanter. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.4. Comparison 3 Dynamic weight bearing exercise low force versus control, Outcome 4 Bone mineral density % change: Ward’s triangle. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.5. Comparison 3 Dynamic weight bearing exercise low force versus control, Outcome 5 Bone mineral density % change: wrist. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.6. Comparison 3 Dynamic weight bearing exercise low force versus control, Outcome 6 Bone mineral density mean regression slope % change: wrist. . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.7. Comparison 3 Dynamic weight bearing exercise low force versus control, Outcome 7 Fractures. . . . Analysis 4.1. Comparison 4 Dynamic weight bearing exercise high force versus control, Outcome 1 Bone mineral density % change: spine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.2. Comparison 4 Dynamic weight bearing exercise high force versus control, Outcome 2 Bone mineral density % change: hip. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.3. Comparison 4 Dynamic weight bearing exercise high force versus control, Outcome 3 Bone mineral density % change: mid femur. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.4. Comparison 4 Dynamic weight bearing exercise high force versus control, Outcome 4 Bone mineral density % change: proximal tibia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.5. Comparison 4 Dynamic weight bearing exercise high force versus control, Outcome 5 Calcium bone index % change: trunk and upper thighs. . . . . . . . . . . . . . . . . . . . . . . . . . . . Exercise for preventing and treating osteoporosis in postmenopausal women (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Analysis 4.6. Comparison 4 Dynamic weight bearing exercise high force versus control, Outcome 6 Bone mineral density % change: trochanter. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.7. Comparison 4 Dynamic weight bearing exercise high force versus control, Outcome 7 Bone mineral density % change: femoral neck. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.8. Comparison 4 Dynamic weight bearing exercise high force versus control, Outcome 8 Bone mineral content % change: spine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.9. Comparison 4 Dynamic weight bearing exercise high force versus control, Outcome 9 Bone mineral content % change: femoral neck. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.10. Comparison 4 Dynamic weight bearing exercise high force versus control, Outcome 10 Bone mineral content % change: wrist. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.11. Comparison 4 Dynamic weight bearing exercise high force versus control, Outcome 11 Bone mineral content % change: ankle. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.12. Comparison 4 Dynamic weight bearing exercise high force versus control, Outcome 12 Bone mineral content % change: tibia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.13. Comparison 4 Dynamic weight bearing exercise high force versus control, Outcome 13 Bone mineral density % change: total body. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.14. Comparison 4 Dynamic weight bearing exercise high force versus control, Outcome 14 Volumetric bone density % change: tibial trabecular. . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.15. Comparison 4 Dynamic weight bearing exercise high force versus control, Outcome 15 Volumetric bone density % change: tibial cortical. . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.16. Comparison 4 Dynamic weight bearing exercise high force versus control, Outcome 16 Fractures. . . Analysis 5.1. Comparison 5 Non-weight bearing exercise low force versus control, Outcome 1 Bone mineral density % change: spine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 5.2. Comparison 5 Non-weight bearing exercise low force versus control, Outcome 2 Bone mineral density % change: total hip. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 5.3. Comparison 5 Non-weight bearing exercise low force versus control, Outcome 3 Bone mineral density % change: femoral neck. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 5.4. Comparison 5 Non-weight bearing exercise low force versus control, Outcome 4 Bone mineral density % change: Ward’s triangle. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 5.5. Comparison 5 Non-weight bearing exercise low force versus control, Outcome 5 Bone mineral density % change: trochanter. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 5.6. Comparison 5 Non-weight bearing exercise low force versus control, Outcome 6 Bone mineral density % change: total body. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 6.1. Comparison 6 Non-weight bearing exercise high force versus control, Outcome 1 Bone mineral density % change: spine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 6.2. Comparison 6 Non-weight bearing exercise high force versus control, Outcome 2 Bone mineral density % change: total hip. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 6.3. Comparison 6 Non-weight bearing exercise high force versus control, Outcome 3 Bone mineral density % change: femoral neck. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 6.4. Comparison 6 Non-weight bearing exercise high force versus control, Outcome 4 Bone mineral density % change: Ward’s triangle. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 6.5. Comparison 6 Non-weight bearing exercise high force versus control, Outcome 5 Bone mineral density % change: trochanter. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 6.6. Comparison 6 Non-weight bearing exercise high force versus control, Outcome 6 Bone mineral density % change: total body. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 7.1. Comparison 7 Combination versus control, Outcome 1 Bone mineral density % change: spine. . . . Analysis 7.2. Comparison 7 Combination versus control, Outcome 2 Bone mineral density % change: total hip. . . Analysis 7.3. Comparison 7 Combination versus control, Outcome 3 Bone mineral density % change: trochanter. . Analysis 7.4. Comparison 7 Combination versus control, Outcome 4 Bone mineral density % change: total body. . Analysis 7.5. Comparison 7 Combination versus control, Outcome 5 Calcium bone index % change: trunk and upper thighs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 7.6. Comparison 7 Combination versus control, Outcome 6 Bone mineral density % change: neck of femur. Analysis 7.7. Comparison 7 Combination versus control, Outcome 7 Bone mineral density % change: Ward’s triangle. Exercise for preventing and treating osteoporosis in postmenopausal women (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Analysis 7.8. Comparison 7 Combination versus control, Outcome 8 Bone mineral density % change: arms. . . . Analysis 7.9. Comparison 7 Combination versus control, Outcome 9 Fractures. . . . . . . . . . . . . . Analysis 8.1. Comparison 8 Dynamic weight bearing exercise high force plus HRT versus HRT, Outcome 1 Bone mineral density % change: proximal tibia. . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 8.2. Comparison 8 Dynamic weight bearing exercise high force plus HRT versus HRT, Outcome 2 Bone mineral density % change: hip. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 8.3. Comparison 8 Dynamic weight bearing exercise high force plus HRT versus HRT, Outcome 3 Bone mineral density % change: mid femur. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 8.4. Comparison 8 Dynamic weight bearing exercise high force plus HRT versus HRT, Outcome 4 Bone mineral density % change: spine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 8.5. Comparison 8 Dynamic weight bearing exercise high force plus HRT versus HRT, Outcome 5 Bone mineral density % change: trochanter. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 8.6. Comparison 8 Dynamic weight bearing exercise high force plus HRT versus HRT, Outcome 6 Bone mineral density % change: femoral neck. . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 8.7. Comparison 8 Dynamic weight bearing exercise high force plus HRT versus HRT, Outcome 7 Bone mineral density % change: total body. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 9.1. Comparison 9 Non-weight bearing exercise high force plus bisphosphonates versus bisphosphonates, Outcome 1 Bone mineral density % change: spine. . . . . . . . . . . . . . . . . . . . . . . . . Analysis 9.2. Comparison 9 Non-weight bearing exercise high force plus bisphosphonates versus bisphosphonates, Outcome 2 Bone mineral density % change: hip. . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 9.3. Comparison 9 Non-weight bearing exercise high force plus bisphosphonates versus bisphosphonates, Outcome 3 Bone mineral density % change: femoral neck. . . . . . . . . . . . . . . . . . . . . . . Analysis 9.4. Comparison 9 Non-weight bearing exercise high force plus bisphosphonates versus bisphosphonates, Outcome 4 Bone mineral density % change: trochanter. . . . . . . . . . . . . . . . . . . . . . . . Analysis 9.5. Comparison 9 Non-weight bearing exercise high force plus bisphosphonates versus bisphosphonates, Outcome 5 Bone mineral density % change: Ward’s triangle. . . . . . . . . . . . . . . . . . . . . . Analysis 9.6. Comparison 9 Non-weight bearing exercise high force plus bisphosphonates versus bisphosphonates, Outcome 6 Bone mineral density % change: total body. . . . . . . . . . . . . . . . . . . . . . . . Analysis 9.7. Comparison 9 Non-weight bearing exercise high force plus bisphosphonates versus bisphosphonates, Outcome 7 Bone mineral content % change: total body. . . . . . . . . . . . . . . . . . . . . . . Analysis 10.1. Comparison 10 Dynamic weight bearing exercise high force plus bisphosphonates versus bisphosphonates, Outcome 1 Bone mineral content % change: spine. . . . . . . . . . . . . . . . . . . . . . Analysis 10.2. Comparison 10 Dynamic weight bearing exercise high force plus bisphosphonates versus bisphosphonates, Outcome 2 Bone mineral content % change: femoral neck. . . . . . . . . . . . . . . . . . . Analysis 10.3. Comparison 10 Dynamic weight bearing exercise high force plus bisphosphonates versus bisphosphonates, Outcome 3 Bone mineral content % change: wrist. . . . . . . . . . . . . . . . . . . . . . Analysis 10.4. Comparison 10 Dynamic weight bearing exercise high force plus bisphosphonates versus bisphosphonates, Outcome 4 Bone mineral content % change: distal tibia. . . . . . . . . . . . . . . . . . . . Analysis 10.5. Comparison 10 Dynamic weight bearing exercise high force plus bisphosphonates versus bisphosphonates, Outcome 5 Bone mineral content % change: tibial shaft. . . . . . . . . . . . . . . . . . . . Analysis 11.1. Comparison 11 Non-weight bearing exercise high force plus antioxidants versus antioxidants, Outcome 1 Bone mineral density % change: spine. . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 11.2. Comparison 11 Non-weight bearing exercise high force plus antioxidants versus antioxidants, Outcome 2 Bone mineral density % change: femoral neck. . . . . . . . . . . . . . . . . . . . . . . Analysis 12.1. Comparison 12 Dynamic weight bearing exercise low force plus Ca2+ versus Ca2+ , Outcome 1 Bone mineral density % change: femoral neck. . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 12.2. Comparison 12 Dynamic weight bearing exercise low force plus Ca2+ versus Ca2+ , Outcome 2 Bone mineral density % change: spine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 12.3. Comparison 12 Dynamic weight bearing exercise low force plus Ca2+ versus Ca2+ , Outcome 3 Bone mineral density % change: trochanter. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 12.4. Comparison 12 Dynamic weight bearing exercise low force plus Ca2+ versus Ca2+ , Outcome 4 Bone mineral density % change: distal tibia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Exercise for preventing and treating osteoporosis in postmenopausal women (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Analysis 12.5. Comparison 12 Dynamic weight bearing exercise low force plus Ca2+ versus Ca2+ , Outcome 5 Bone mineral density % change: Ward’s triangle. . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 13.1. Comparison 13 Non-weight bearing exercise low force plus calcium versus calcium, Outcome 1 Bone mineral density % change: spine. . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 13.2. Comparison 13 Non-weight bearing exercise low force plus calcium versus calcium, Outcome 2 Bone mineral density % change: total hip. . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 13.3. Comparison 13 Non-weight bearing exercise low force plus calcium versus calcium, Outcome 3 Bone mineral density % change: femoral neck. . . . . . . . . . . . . . . . . . . . . . . . . Analysis 13.4. Comparison 13 Non-weight bearing exercise low force plus calcium versus calcium, Outcome 4 Bone mineral density % change: trochanter. . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 13.5. Comparison 13 Non-weight bearing exercise low force plus calcium versus calcium, Outcome 5 Bone mineral density % change: total body. . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 14.1. Comparison 14 Non-weight bearing exercise high force plus calcium versus calcium, Outcome 1 Bone mineral density % change: femoral neck. . . . . . . . . . . . . . . . . . . . . . . . . Analysis 14.2. Comparison 14 Non-weight bearing exercise high force plus calcium versus calcium, Outcome 2 Bone mineral density % change: trochanter. . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 14.3. Comparison 14 Non-weight bearing exercise high force plus calcium versus calcium, Outcome 3 Bone mineral density % change: total hip. . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 14.4. Comparison 14 Non-weight bearing exercise high force plus calcium versus calcium, Outcome 4 Bone mineral density % change: spine. . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 14.5. Comparison 14 Non-weight bearing exercise high force plus calcium versus calcium, Outcome 5 Bone mineral density % change: total body. . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 15.1. Comparison 15 Dynamic weight bearing exercise low force plus calcium/VitD versus calcium/VitD, Outcome 1 Bone mineral density % change: spine. . . . . . . . . . . . . . . . . . . . . . Analysis 15.2. Comparison 15 Dynamic weight bearing exercise low force plus calcium/VitD versus calcium/VitD, Outcome 2 Bone mineral density % change:wrist. . . . . . . . . . . . . . . . . . . . . . APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Exercise for preventing and treating osteoporosis in postmenopausal women (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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[Intervention Review]

Exercise for preventing and treating osteoporosis in postmenopausal women Tracey E Howe1 , Beverley Shea2 , Lesley J Dawson3 , Fiona Downie3 , Ann Murray4 , Craig Ross5 , Robin T Harbour6 , Lynn M Caldwell Gisela Creed8

7,

1 School

of Health & Life Sciences, Glasgow Caledonian University, Glasgow, UK. 2 CIET, Institute of Population Health, University of Ottawa, Ottawa, Canada. 3 Department of Physiotherapy, NHS Forth Valley, Stirling, UK. 4 NHS Ayrshire and Arran, Kilmarnock, UK. 5 Physiotherapy Service for Osteoporosis, NHS Greater Glasgow & Clyde, Glasgow, UK. 6 Scottish Intercollegiate Guidelines network (SIGN), Edinburgh, UK. 7 Knowledge Services Group, NHS Education for Scotland, Glasgow, UK. 8 Academic Department of Geriatric Medicine, Glasgow University, Glasgow, UK Contact address: Tracey E Howe, School of Health & Life Sciences, Glasgow Caledonian University, Scottish Centre for Evidence Based Care of Older People, Glasgow, Scotland, G4 0BA, UK. [email protected]. Editorial group: Cochrane Musculoskeletal Group. Publication status and date: New search for studies and content updated (conclusions changed), published in Issue 7, 2011. Review content assessed as up-to-date: 2 January 2011. Citation: Howe TE, Shea B, Dawson LJ, Downie F, Murray A, Ross C, Harbour RT, Caldwell LM, Creed G. Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database of Systematic Reviews 2011, Issue 7. Art. No.: CD000333. DOI: 10.1002/14651858.CD000333.pub2. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT Background Osteoporosis is a condition resulting in an increased risk of skeletal fractures due to a reduction in the density of bone tissue. Treatment of osteoporosis typically involves the use of pharmacological agents. In general it is thought that disuse (prolonged periods of inactivity) and unloading of the skeleton promotes reduced bone mass, whereas mechanical loading through exercise increases bone mass. Objectives To examine the effectiveness of exercise interventions in preventing bone loss and fractures in postmenopausal women. Search methods During the update of this review we updated the original search strategy by searching up to December 2010 the following electronic databases: the Cochrane Musculoskeletal Group’s Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2010 Issue 12); MEDLINE; EMBASE; HealthSTAR; Sports Discus; CINAHL; PEDro; Web of Science; Controlled Clinical Trials; and AMED. We attempted to identify other studies by contacting experts, searching reference lists and searching trial registers. Selection criteria All randomised controlled trials (RCTs) that met our predetermined inclusion criteria. Data collection and analysis Pairs of members of the review team extracted the data and assessed trial quality using predetermined forms. For dichotomous outcomes (fractures), we calculated risk ratios (RRs) using a fixed-effect model. For continuous data, we calculated mean differences (MDs) of the percentage change from baseline. Where heterogeneity existed (determined by the I2 statistic), we used a random-effects model. Exercise for preventing and treating osteoporosis in postmenopausal women (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Exercise for preventing and treating osteoporosis in postmenopausal women (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Main results Forty-three RCTs (27 new in this update) with 4320 participants met the inclusion criteria. The most effective type of exercise intervention on bone mineral density (BMD) for the neck of femur appears to be non-weight bearing high force exercise such as progressive resistance strength training for the lower limbs (MD 1.03; 95% confidence interval (CI) 0.24 to 1.82). The most effective intervention for BMD at the spine was combination exercise programmes (MD 3.22; 95% CI 1.80 to 4.64) compared with control groups. Fractures and falls were reported as adverse events in some studies. There was no effect on numbers of fractures (odds ratio (OR) 0.61; 95% CI 0.23 to 1.64). Overall, the quality of the reporting of studies in the meta-analyses was low, in particular in the areas of sequence generation, allocation concealment, blinding and loss to follow-up. Authors’ conclusions Our results suggest a relatively small statistically significant, but possibly important, effect of exercise on bone density compared with control groups. Exercise has the potential to be a safe and effective way to avert bone loss in postmenopausal women.

PLAIN LANGUAGE SUMMARY Exercise for preventing and treating osteoporosis in postmenopausal women This summary of a Cochrane review presents what we know from research about the effect of exercise on bone mass in postmenopausal women. The review shows that for postmenopausal women -

Exercise will improve bone mineral density slightly.

-

Exercise will reduce the chances of having a fracture slightly.

These results might have happened by chance. What is osteoporosis and exercise Bone is a living, growing part of your body. Throughout your lifetime, new bone cells grow and old bone cells break down to make room for the new, stronger bone. When you have osteoporosis, the old bone breaks down faster than the new bone can replace it. As this happens, the bones lose minerals (such as calcium). This makes bones weaker and more likely to break even after a minor injury, like a little bump or fall. Exercise interventions are typically those that stress or mechanically load bones (when bones support the weight of the body or when movement is resisted for example when using weights) and include aerobics, strength training, walking and tai chi. Best estimate of what happens to postmenopausal women who exercise Bone mineral density at the spine People who exercised had on average 0.85% less bone loss than those who didn’t exercise. People who engaged in combinations of exercise types had on average 3.2% less bone loss than those who did not exercise. 2

Bone mineral density at the hip People who exercised had on average 1.03% less bone loss than those who didn’t exercise. People who exercised by strength training had on average 1.03% less bone loss. Fractures

Exercise for preventing and treating osteoporosis in postmenopausal women (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

S U M M A R Y O F F I N D I N G S F O R T H E M A I N C O M P A R I S O N [Explanation]

Exercise for preventing and treating osteoporosis in postmenopausal women Patient or population: preventing and treating osteoporosis in postmenopausal women Settings: Intervention: exercise Outcomes

Illustrative comparative risks* (95% CI)

Assumed risk

Corresponding risk

Control

Exercise

Total number of frac- Study population tures 106 per 1000 radiographs

Relative effect (95% CI)

No. of Participants (studies)

Quality of the evidence (GRADE)

Comments

OR 0.61 (0.23 to 1.64)

539 (4 studies)

⊕⊕⊕⊕ high

Absolute difference = 4% Not statistically significant.

67 per 1000 (27 to 163)

Bone mineral density % The mean bone minchange: spine eral density % change: spine ranged across control groups from -4.38 to 1.05 %

The mean bone mineral density % change: spine in the intervention groups was 0.85 % higher (0.62 to 1.07 higher)

1441 (24 studies)

⊕⊕⊕⊕ high

Bone mineral density % The mean bone minchange: femoral neck eral density % change: femoral neck ranged across control groups from -3.19 to 3.12 %

The mean bone mineral density % change: femoral neck in the intervention groups was 0.08 % lower (1.08 lower to 0.92 higher)

1338 (19 studies)

⊕⊕

low1

3

Exercise for preventing and treating osteoporosis in postmenopausal women (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Bone mineral density % The mean bone mineral change: total hip density % change: total hip ranged across control groups from -2.18 to 2.61 %

The mean bone mineral density % change: total hip in the intervention groups was 0.41 % higher (0.64 lower to 1.45 higher)

863 (13 studies)

⊕⊕⊕⊕ high

Bone mineral density % The mean bone minchange: trochanter eral density % change: trochanter ranged across control groups from -1.62 to 2.94 %

The mean bone mineral density % change: trochanter in the intervention groups was 1.03 % higher (0.56 to 1.49 higher)

815 (10 studies)

⊕⊕⊕⊕ high

Adverse events: Falls

see comment

see comment

not estimable

378 (3 studies)

see comment

Reported as adverse events there were 75 falls reported in the exercise groups and 55 in the control groups2

Other adverse events

see comment

see comment

not estimable

907 (11 studies)

see comment

Events included muscle soreness, joint pain, headache, itching There were 60 events reported in the exercise groups and 5 in the control groups3

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio

4

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GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Very low quality: we are very uncertain about the estimate 1 2 3

Significant heterogeneity observed even with random effects model. Reported as total number of falls but individuals may have had more than one fall. Events reported as adverse for participants in intervention groups, generally no mention of event monitoring in control groups.

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BACKGROUND

Description of the condition Osteoporosis is a condition resulting in an increased risk of skeletal fractures due to a reduction in the density of bone tissue (CDC 1991). The most common clinical manifestations of osteoporosis are fractures of the hip, vertebrae or wrist. Osteoporotic-related fractures are responsible for excess mortality, morbidity, chronic pain, reduction in quality of life, admission to long-term care and health and social care costs (Papaioannou 2010). For women at the age of 50 years in developed countries, the remaining lifetime possibility of osteoporotic fractures exceeds 40%; the remaining lifetime probability for hip fracture alone exceeds 20% (Bessette 2008). The excess mortality associated with a hip fracture has been estimated to be 20% (Cooper 1993). The number of osteoporoticrelated fractures is certain to increase as a result of the ageing population (WHO 1994). Prevention of osteoporotic-related fractures is based on the ability to estimate fracture probability by means of risk factor assessment. The quality of bone, (the total characteristics of the bone that influence the bone’s resistance to fracture), is determined by a number of factors including bone geometry, cortical thickness and porosity, trabecular bone morphology and intrinsic properties of bony tissue. Low bone mass, detected by bone densitometry, is one of the most important risk factors. Bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA) is reported to account for 60% to 70% of the variation in bone strength (Ammann 2003), and prospective studies have documented that the lifetime risk of an osteoporotic-related fracture increases 1.5 to 3 times with each standard deviation (SD) decrease in bone density (Cummings 1993). However Zebaze 2010 reported that most bone loss is cortical, not trabecular, and occurs after the age of 65 years; and that the resulting structural decay, including the magnitude of intracortical remodelling and intracortical porosity, are poorly captured by current measurement methods. Although measurements of BMD contribute to the prediction of fracture risk they cannot identify individuals who will have a fracture (Marshall 1996) as many fractures, particularly in older populations, are results of falls which are influenced by environmental and other medical causes, e.g. impaired visual function, muscle strength and balance (Gillespie 2009). The treatment of hip fracture and the hospitalisation required following all types of fracture account for most of the economic costs associated with osteoporosis (Cooper 1993). Therefore, the prevention of fractures is the primary goal of intervention. See other Cochrane systematic reviews for pharmacological interventions for osteoporosis: alendronate (Wells 2008a); etidronate (Wells 2008b); fluoride (Haguenauer 2004); risedronate (Wells 2008c); and strontium renalate (Cranney 2006).

Description of the intervention Various exercise interventions, designed to stimulate bone growth and preserve bone mass have been described and evaluated. Interventions are typically those that stress or mechanically load bones (when bones support the weight of the body or when movement is resisted, for example when using weights) and include aerobics, weight bearing and resistance exercises.

How the intervention might work In general, it is thought that disuse (not using the limbs or prolonged periods of inactivity) and unloading of the skeleton promotes reduced bone mass (Zerwekh 1998), whereas loading promotes increased bone mass. The effects of mechanical loading have been demonstrated in athletes undertaking high-impact exercise (Taaffe 1997) and in rats (Robling 2002). Mechanical loading through exercise has the potential to be a safe and effective way to avert or delay the onset of osteoporosis in postmenopausal women. The previous version of this review (Bonaiuti 2002) concluded that exercise has beneficial effects on bone density of the hip and spine, although long term-studies including fracture data are rare. In addition, strength and balance exercises contribute to fracture risk reduction through their efficacy in reducing falls risk (Gillespie 2009).

Why it is important to do this review The high prevalence and staggering costs (Burge 2007) of osteoporotic-related fractures in postmenopausal women means prevention and management of this disease is important. There continues to be much interest in the effects of exercise on bone as a nonpharmacological intervention. A systematic review is required to identify the number of new trials in this area and summarise the evidence for healthcare professionals, policy makers, researchers and others with an interest in this area.

OBJECTIVES To examine the effectiveness of exercise in preventing bone loss in postmenopausal women by determining whether or not exercise slows bone loss and has a beneficial effect on the axial (the skull, spine and rib cage) and appendicular (the bones of the limbs and pelvis) bone density in postmenopausal women.

METHODS

Criteria for considering studies for this review

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We included studies where participants were healthy postmenopausal women (including those with previous fractures) aged between 45 and 70 years.

and Haynes 1994 and the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). During this current update of the review, we undertook a further search. We searched the following electronic databases; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2010); MEDLINE (Appendix 1); EMBASE (Appendix 2); HealthSTAR; Sports Discus; CINAHL (Appendix 3); PEDro (Appendix 4); Web of Science; Controlled Clinical Trials (Appendix 5); and AMED (Appendix 6) (all to December 2010).

Types of interventions

Searching other resources

We included all RCTs with an exercise programme (e.g. walking, callisthenics and resisted strengthening) assumed to be adequate to improve aerobic capacity, or both aerobic capacity and muscle strength compared to standard therapy (e.g. usual activity or placebo with or without pharmacological consumption).

In addition, we searched the reference lists of included trials and trials registers, and contacted content experts for additional studies and data.

Types of studies We considered all randomised controlled clinical trials (RCTs) of exercise in healthy postmenopausal women. Types of participants

Types of outcome measures

Major outcomes

• Number of incident fractures: vertebral and non-vertebral (hip and wrist). Secondary outcomes

• Bone mass including BMD, bone mineral content (BMC), or calcium bone index (CaBI) immediately postintervention and at follow-up. BMD was measured by Single-Photon Absorptiometry (SPA), Dual-Photon Absorptiometry (DPA), Quantitative Computerised Tomography (QCT) or DXA at baseline, immediately postintervention and at follow-up. All results were converted to the percentage change of BMD from baseline values. The difference between the percentage lost in the exercise group and the percentage lost in the control group was used as the measure of effect in pooling the data. • Serious adverse events including death. • Minor adverse events including falls.

Search methods for identification of studies Electronic searches To identify exercise trials, we searched the following five electronic databases: the Cochrane Musculoskeletal Group’s Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); MEDLINE; EMBASE; and Current Contents from 1966 to January 2000 with no language restrictions, according to the methods suggested by Dickersin 1994

Data collection and analysis

Selection of studies Following an a priori protocol, at least two review authors (BS, TH, LD and FD) independently reviewed the eligibility criteria for abstracts for inclusion in this review. We screened all titles and/or abstracts generated by the searches for potentially relevant studies based on the following criteria: the type of study; type of participants; type of intervention; and type of outcome measurements. We assessed the full-length articles of the selected titles and/or abstracts for eligibility (for a full description see Criteria for considering studies for this review). We resolved disagreements by consensus or third-party adjudication. Data extraction and management Pairs of members of the review team used a customised data extraction tool, tested prior to use, to independently extract data. We resolved disagreements by consensus or third-party adjudication. We attempted to contact authors of studies where there was inadequate reporting of data, to enable clarification and where appropriate, to allow pooling. Where available and appropriate, we presented quantitative data for the outcomes listed in the inclusion criteria in the analyses. Where studies reported standard errors (SEs) of the means, we obtained SDs by multiplying SEs of means by the square root of the sample size. In order to assess efficacy, we extracted raw data for outcomes of interest (means and SDs for continuous outcomes and number of events for dichotomous outcomes) where available in the published reports. Wherever we converted or imputed reported data, we recorded this in the notes section of the Characteristics of included studies. All trials reported continuous outcomes as end-point scores (i.e. mean and SD of the variable at follow-up, assuming baseline comparability).

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Assessment of risk of bias in included studies

Data synthesis

We assessed risk of bias for each included study using the Cochrane Collaboration’s ’Risk of bias’ tool (Higgins 2011). Pairs of members of the review team reported the following six key domains: sequence generation; allocation concealment; blinding; incomplete outcome data; selective outcome reporting; and “other bias” (comparability of treatment and control group at entry, and appropriateness of duration of surveillance). In cases of disagreement between the review authors, we used consensus to make a decision. The final assessments for all included studies are presented in a ’risk of bias’ table (see Characteristics of included studies).

We used Cochrane Review Manager software to meta-analyse the statistics as described below (RevMan 2011). We used 95% CIs for all outcomes.

Measures of treatment effect For each trial, we calculated risk ratios (RRs) and 95% CIs for dichotomous outcomes, and mean differences (MDs) and 95% CIs for continuous outcomes (reporting mean and SD or standard error (SE) of the mean). Where appropriate, we pooled results of comparable groups of trials using the fixed-effect model and 95% CIs.

Unit of analysis issues We reported the level at which randomisation occurred in the included studies as specified by the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2011). Possible variations in study designs include cluster randomised trials, cross-over trials, multiple observations, re-occurring events, multiple treatments and multiple intervention groups.

Dealing with missing data If we discovered missing data during data extraction, we attempted to contact the original investigators of the study to request the required information. We anticipated that it may also have been necessary to conduct a sensitivity analysis if assumptions were made (Deeks 2011). We have also described the potential effect of missing data upon conclusions drawn from this review.

Assessment of heterogeneity We tested heterogeneity between comparable trials using a standard Chi2 test and considered heterogeneity statistically significant at P < 0.1 after due consideration of the value of the I2 statistic; a value greater than 50% may indicate substantial heterogeneity.

Assessment of reporting biases If there were sufficient studies, we intended to assess the possibility of publication bias with funnel plots.

Continuous outcomes We calculated mean differences (MDs) using a fixed-effect model as we measured outcomes on standard scales. We explored possible reasons for heterogeneity in terms of prevention versus treatment studies (primary versus secondary prevention), trial quality, differing populations and exercise programmes. We used a randomeffects model to further analyse the results which were determined to indicate substantial heterogeneity (i.e. after due consideration of the value of the I2 statistic, a value greater than 50%).

Dichotomous outcomes For interpretation of the dichotomous outcome measures in this review, we selected the RR using a random-effects model, since this is the most appropriate statistic for the interpretation of pooled data where the event is common and where there is statistical heterogeneity between trials (Deeks 1998). We performed appropriate statistical analysis using Review Manager (RevMan 2011) in accordance with the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2011).

Subgroup analysis and investigation of heterogeneity In the presence of heterogeneity, we pooled the results of comparable groups using the random-effects model and 95% CIs. We performed separate outcome analyses to determine the effectiveness of different categories of exercise interventions versus control. Where the data allowed, we also anticipated performing separate outcome analyses to test the following hypotheses: 1. effectiveness is not dependent on the duration and/or intensity of the physical activity/exercise intervention; 2. effectiveness is not dependent on the setting in which the physical activity/exercise intervention is delivered; and 3. effectiveness is not dependent on the level or type of supervision of the physical activity/exercise intervention.

Sensitivity analysis We anticipated that we would undertake sensitivity analyses, when indicated, to investigate the effects of methodological quality, for example, allocation concealment and intention-to-treat (ITT) analysis or where cluster randomised trials are combined with each other or with other studies in a meta-analysis.

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Grading of evidence and summary of findings table Major outcomes (including benefits and adverse events) are presented in the Summary of findings for the main comparison which provides information on the quality of evidence and the magnitude of the intervention effect, as well as a summary of the main outcome data. We have also presented an assessment of the overall quality of evidence per outcome (high, moderate, low and very low) using the GRADE approach as outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Schünemann 2011).

2010; Sinaki 1989; Tolomio 2009). The attendance rate ranged from 48% (Preisinger 1995) to 93% (Bemben 2000) and the adherence rate to the exercise programmes ranged from 39% (Prince 1995) to 95% (Bocalini 2009). Thirteen studies reported the accuracy of the assessing instrument (i.e. the test-retest reliability) (Grove 1992; Hatori 1993; Lau 1992; Lord 1996; Martin 1993; Nelson 1994; Preisinger 1995; Prince 1991; Prince 1995; Pruitt 1996; Revel 1993; Sinaki 1989; Smidt 1992). Instrument accuracy ranged from 0.4% (Hatori 1993) to 3% (Grove 1992). Setting

RESULTS

Description of studies See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of studies awaiting classification; Characteristics of ongoing studies. Forty-three RCTs (27 new in this update) with 4320 participants met the inclusion criteria. Although included in the original version of this review, we excluded (Kerr 1996) from this update because participants were their own control, with one side of body randomised to a different exercise type. Forty-one of the 43 included studies were published in English, one in German (Von Stengel 2009) and one in Italian (Tolomio 2009). Exercise interventions For details of the content of individual interventions see Characteristics of included studies. Many factors influence the effectiveness of exercise interventions: 1. attendance; 2. adherence to the programme; 3. accuracy of the assessment system; 4. type of exercise; and 5. duration, intensity, frequency and length of exercise programme. The World Health Organization (WHO) defines adherence as “the extent to which a person’s behavior such as taking medication, following a diet, executing lifestyle changes like exercising, corresponds with agreed recommendations from a health care provider”, (WHO 2003) this is clearly different to attendance. The quality of the reporting of these factors varied in the 43 studies included in this review.

The studies included participants from North America (Bravo 1996; Bemben 2000; Chilibeck 2002; Chow 1987; Chubak 2006; Chuin 2009; Going 2003; Grove 1992; Maddalozzo 2007; Martin 1993; Metcalfe 2001; Nelson 1994; Newstead 2004; Papaioannou 2003; Pruitt 1996; Rubin 2004; Russo 2003; Sinaki 1989; Smidt 1992), Australia (Kerr 2001; Lord 1996; Prince 1991; Prince 1995), Europe (Bergstrom 2008; Cheng 2002; Ebrahim 1997; Englund 2005; Karinkanta 2007; Korpelainen 2006; Preisinger 1995; Revel 1993; Tolomio 2009; Uusi-Rasi 2003; Verschueren 2004; Von Stengel 2009), Japan (Hatori 1993; Iwamoto 2001; Iwamoto 2005; Sakai 2010), China (Chan 2004; Lau 1992) and Brazil (Bocalini 2009; Brentano 2008). Length of exercise programmes The length of the exercise programmes varied in the included studies; 10 were less than 12 months long (Bemben 2000; Bocalini 2009; Brentano 2008; Chuin 2009; Hatori 1993; Lau 1992; Russo 2003; Sakai 2010; Tolomio 2009; Verschueren 2004); 26 were 12 months long (Bergstrom 2008; Bravo 1996; Chan 2004; Chilibeck 2002; Chow 1987; Chubak 2006; Englund 2005; Going 2003; Grove 1992; Iwamoto 2001; Iwamoto 2005; Karinkanta 2007; Kerr 2001; Lord 1996; Maddalozzo 2007; Martin 1993; Metcalfe 2001; Nelson 1994; Newstead 2004; Papaioannou 2003; Pruitt 1996; Revel 1993; Rubin 2004; Smidt 1992; Uusi-Rasi 2003; Von Stengel 2009); and seven were greater than 12 months (Ebrahim 1997; Kerr 2001; Korpelainen 2006; Preisinger 1995; Prince 1991; Prince 1995; Sinaki 1989). Number of years postmenopausal The number of years postmenopausal was reported in 15 studies (Bemben 2000; Bravo 1996; Chan 2004; Chilibeck 2002; Chubak 2006; Going 2003; Grove 1992; Maddalozzo 2007; Nelson 1994; Preisinger 1995; Prince 1991; Revel 1993; Russo 2003; Uusi-Rasi 2003; Verschueren 2004).

Compliance/adherence Thirty-three studies reported compliance/adherence to the programmes and 10 did not (Bravo 1996; Brentano 2008; Chuin 2009; Hatori 1993; Iwamoto 2005; Lau 1992; Russo 2003; Sakai

Exercise interventions All the exercise interventions described were land based except in one study (Tolomio 2008) which included both land and water

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based exercise. We categorised the exercise interventions into the following six categories. • Static weight bearing (SWB); including single leg standing. • Dynamic weight bearing exercise low force (DWBLF); including walking and Tai chi. • Dynamic weight bearing exercise high force (DWBHF); including jogging, jumping, running, dancing and vibration platform. • Non-weight bearing exercise low force (NWBLF); e.g. low load, high repetition strength training. • Non-weight bearing exercise high force (NWBHF); e.g. progressive resisted strength training. • Combination (COMB); more than one of the above exercise interventions. Exercise training consisted of: DWBLF in 12 studies (Bravo 1996; Chan 2004; Chow 1987; Ebrahim 1997; Grove 1992; Hatori 1993; Lau 1992; Lord 1996; Martin 1993; Preisinger 1995; Prince 1991; Prince 1995); DWBHF in 11 studies (Cheng 2002; Going 2003; Grove 1992; Iwamoto 2005; Karinkanta 2007; Maddalozzo 2007; Newstead 2004; Rubin 2004; Russo 2003; Uusi-Rasi 2003; Verschueren 2004); NWBLF in six studies (Bemben 2000; Brentano 2008; Kerr 2001; Pruitt 1996; Revel 1993; Sinaki 1989); NWBHF in nine studies (Bemben 2000; Brentano 2008; Bocalini 2009; Chilibeck 2002; Chuin 2009; Kerr 2001; Nelson 1994; Pruitt 1996; Smidt 1992); COMB in 11 studies (Bergstrom 2008; Chow 1987; Chubak 2006; Englund 2005; Iwamoto 2001; Karinkanta 2007; Korpelainen 2006; Metcalfe 2001; Papaioannou 2003; Tolomio 2009; Von Stengel 2009); and SWB in one study (Sakai 2010). It should be noted that some studies included more than one exercise intervention arm. Frequency of the exercise intervention The frequency of the sessions for the majority of studies was two or three times per week. The exception being three studies where participants had daily exercise sessions (Iwamoto 2001; Revel 1993; Sakai 2010) and seven who had four to six sessions per week (Bergstrom 2008; Chan 2004; Cheng 2002; Lau 1992; Prince 1995; Sinaki 1989; Smidt 1992). Content of the exercise intervention The content of the training session was reported in five studies (Lau 1992; Lord 1996; Preisinger 1995; Prince 1991; Prince 1995) and two studies assessed the effect of the repetition of only one exercise (Revel 1993; Sinaki 1989). There were five studies that described that exercise intensity was determined by maximal heart rate ( Bravo 1996; Chow 1987; Ebrahim 1997; Hatori 1993; Martin 1993), and three studies reported how the maximum strength was measured (Nelson 1994; Pruitt 1996; Smidt 1992). One study measured the exercise intensity in relation to body weight (Grove 1992).

Controls In all but twelve studies the controls were invited to continue their usual activity without any exercise prescription. One study reported the control group performing 45 minute stretching sessions once a week (Chubak 2006); one performing upper limb exercises only (Ebrahim 1997); and one performing gentle exercise and relaxation (Von Stengel 2009). In five studies controls were divided into usual activity with drug interventions or usual activity alone (Lau 1992; Martin 1993; Maddalozzo 2007; Prince 1991; Prince 1995). A placebo device was used in only one study (Rubin 2004), and there were three studies which did not report on the control group (Englund 2005; Hatori 1993; Papaioannou 2003).

Outcome measures Fracture rate was a primary outcome measure in only one trial (Iwamoto 2005), but was reported as an adverse event at followup in three (Chan 2004; Karinkanta 2007; Korpelainen 2006). Falls were reported as adverse events in four trials (Chan 2004; Ebrahim 1997; Iwamoto 2005; Karinkanta 2007). BMD was measured at the lumbar spine in 30 studies (Bemben 2000; Bergstrom 2008; Bocalini 2009; Bravo 1996; Chan 2004; Chilibeck 2002; Chuin 2009; Ebrahim 1997; Englund 2005; Going 2003; Grove 1992; Hatori 1993; Iwamoto 2001; Kerr 2001; Lau 1992; Lord 1996; Maddalozzo 2007; Martin 1993; Metcalfe 2001; Nelson 1994; Newstead 2004; Papaioannou 2003; Prince 1995; Pruitt 1996; Revel 1993; Rubin 2004; Sinaki 1989; Smidt 1992; Uusi-Rasi 2003; Von Stengel 2009). BMD was measured at the hip in 30 studies (Bemben 2000; Bergstrom 2008; Bocalini 2009; Bravo 1996; Brentano 2008; Chan 2004; Cheng 2002; Chilibeck 2002; Chuin 2009; Ebrahim 1997; Englund 2005; Going 2003; Kerr 2001; Korpelainen 2006; Lau 1992; Lord 1996; Maddalozzo 2007; Metcalfe 2001; Nelson 1994; Newstead 2004; Papaioannou 2003; Prince 1995; Pruitt 1996; Rubin 2004; Sakai 2010; Smidt 1992; Tolomio 2009; Uusi-Rasi 2003; Verschueren 2004; Von Stengel 2009). These were subdivided into the following sites: femoral neck (Bemben 2000; Bocalini 2009; Bravo 1996; Brentano 2008; Chan 2004; Chuin 2009; Ebrahim 1997; Englund 2005; Going 2003; Kerr 2001; Korpelainen 2006; Lau 1992; Lord 1996; Maddalozzo 2007; Nelson 1994; Newstead 2004; Papaioannou 2003; Pruitt 1996; Sakai 2010; Tolomio 2009; Uusi-Rasi 2003); intertrochanteric (Brentano 2008; Sakai 2010); trochanter (Bemben 2000; Brentano 2008; Chan 2004; Chilibeck 2002; Englund 2005; Going 2003; Kerr 2001; Korpelainen 2006; Lord 1996; Maddalozzo 2007; Sakai 2010; Smidt 1992; Uusi-Rasi 2003); Ward’s Triangle (Bemben 2000; Brentano 2008; Chilibeck 2002; Englund 2005; Lau 1992; Pruitt 1996; Sakai 2010; Smidt 1992); and total hip (Bemben 2000; Bergstrom 2008; Chilibeck 2002; Kerr 2001; Korpelainen 2006; Maddalozzo 2007; Newstead 2004; Pruitt 1996; Tolomio 2009; Verschueren 2004; Von Stengel

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2009). BMD was also measured at the distal radius (Korpelainen 2006; Preisinger 1995; Rubin 2004; Uusi-Rasi 2003); forearm (Kerr 2001; Martin 1993; Prince 1991); tibia (Chan 2004; Cheng 2002); ankle (Prince 1995); and total body (Bemben 2000; Chilibeck 2002; Chubak 2006; Englund 2005; Going 2003; Kerr 2001; Newstead 2004; Verschueren 2004). Other outcome measures included: BMC (Englund 2005; Karinkanta 2007; Nelson 1994; Uusi-Rasi 2003); cortical bone density (Cheng 2002; Karinkanta 2007); trabecular bone density (Russo 2003); CaBI (Chow 1987); body mass (Martin 1993); muscle strength (Metcalfe 2001); and rate of falls (Von Stengel

2009). Other adverse events were reported by 11 studies (Chow 1987; Ebrahim 1997; Grove 1992; Karinkanta 2007; Korpelainen 2006; Nelson 1994; Pruitt 1996; Revel 1993; Rubin 2004; Russo 2003; Uusi-Rasi 2003) and included muscle soreness, joint pain, headache and itching. Results of the search From the search we found 936 references to potential studies. We discussed and resolved disagreements by reading the full text of the paper. We retrieved a total of 90 potential relevant trials for further classification (see PRISMA flow chart Figure 1).

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Figure 1. Study flow diagram.

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Included studies Forty-three RCTs (27 new in this update) with 4320 participants met the inclusion criteria. On further scrutiny of the included studies from the original version (Mayoux-Benhamou 1997) was actually follow-up data for another included study (Revel 1993). Forty-one of these 43 included studies were published in English, one in German (Von Stengel 2009) and one in Italian (Tolomio 2009). Three studies are awaiting classification and one trial is ongoing. We assessed all study designs as not affecting unit of analysis, for example we reported no cluster randomised trials or cross-over trials. Excluded studies Thirty-one studies did not meet the inclusion criteria as published in our a priori protocol. On further scrutiny of the included studies from the original version we excluded one study (Kerr 1996) because participants were their own control, with one side of body randomised to a different exercise type.

Risk of bias in included studies

Pairs of review authors judged the following key domains as ’low risk’, ‘high risk’ or ‘unclear risk of bias’: • random sequence generation; • allocation concealment; • incomplete outcome data; • selective reporting; • blinding (participant); • blinding (assessor); and • “other bias” (comparability of treatment and control group at entry, and appropriateness of duration of surveillance). In cases of disagreement between the review authors, we made a decision based on consensus. The methodological quality summary for each included study is presented in Figure 2 and the review authors’ judgements about each methodological quality item are presented as percentages across all included studies in Figure 3. We assessed the overall risk of bias as ’low’ for 13 studies (Bergstrom 2008; Bravo 1996; Cheng 2002; Chilibeck 2002; Chow 1987; Chubak 2006; Ebrahim 1997; Karinkanta 2007; Korpelainen 2006; Lau 1992; Lord 1996; Uusi-Rasi 2003; Verschueren 2004) and ’high risk of bias’ for four studies (Metcalfe 2001; Prince 1991; Prince 1995; Rubin 2004).

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Figure 2. Methodological quality summary: review authors’ judgements about each methodological quality item for each included study.

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Figure 3. Methodological quality graph: review authors’ judgements about each methodological quality item presented as percentages across all included studies.

Allocation In the original version of the review only one study had clearly used a proper method of randomisation (Lau 1992). In this update 16 studies adequately described sequence generation (’low risk of bias’) (Bergstrom 2008; Bravo 1996; Cheng 2002; Chow 1987; Chubak 2006; Ebrahim 1997; Karinkanta 2007; Kerr 2001; Korpelainen 2006; Lau 1992; Prince 1991; Prince 1995; Rubin 2004; Russo 2003; Sakai 2010; Verschueren 2004) and eleven studies adequately described allocation concealment (’low risk of bias’) (Chilibeck 2002; Chow 1987; Chubak 2006; Ebrahim 1997; Karinkanta 2007; Korpelainen 2006; Lau 1992; Lord 1996; Prince 1991; Prince 1995; Rubin 2004). The other studies did not clearly describe these methods (’unclear risk of bias’).

Blinding It is difficult to ensure blinding of participants in studies of exercise interventions. Only one study adequately blinded participants for the type of exercise intervention (’low risk of bias’) (Rubin 2004), there was an ’unclear risk of bias’ in 15 studies (Bravo 1996; Brentano 2008; Cheng 2002; Chilibeck 2002; Chubak 2006; Ebrahim 1997; Going 2003; Hatori 1993; Iwamoto 2001;

Karinkanta 2007; Lau 1992; Lord 1996; Martin 1993; Nelson 1994; Uusi-Rasi 2003) and participants were not blinded in 27 studies (’high risk of bias’). Fourteen studies adequately blinded assessors to type of exercise intervention (’low risk of bias’) (Bocalini 2009; Bravo 1996; Chilibeck 2002; Chow 1987; Chubak 2006; Hatori 1993; Korpelainen 2006; Papaioannou 2003; Preisinger 1995; Revel 1993; Rubin 2004; Sinaki 1989; Uusi-Rasi 2003; Verschueren 2004), there was an ’unclear risk of bias’ in 28 studies and assessors were not blinded in one study (’high risk of bias’) (Ebrahim 1997).

Incomplete outcome data Fifteen studies were judged as appropriately addressing incomplete outcome data (’low risk of bias’) (Bergstrom 2008; Bravo 1996; Chow 1987; Chubak 2006; Ebrahim 1997; Going 2003; Karinkanta 2007; Korpelainen 2006; Lord 1996; Metcalfe 2001; Nelson 1994; Sinaki 1989; Tolomio 2009; Uusi-Rasi 2003; Von Stengel 2009), there was an ’unclear risk of bias’ for 26 studies (Bocalini 2009; Brentano 2008; Chan 2004; Cheng 2002; Chilibeck 2002; Chuin 2009; Englund 2005; Grove 1992; Iwamoto 2001; Iwamoto 2005; Kerr 2001; Lau 1992;

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Maddalozzo 2007; Martin 1993; Newstead 2004; Papaioannou 2003; Preisinger 1995; Prince 1991; Prince 1995; Pruitt 1996; Revel 1993; Rubin 2004; Russo 2003; Sakai 2010; Smidt 1992; Verschueren 2004) and two studies were judged as not addressing incomplete outcome data (’high risk of bias’) (Bemben 2000; Hatori 1993).

Selective reporting Insufficient information was available to permit judgement of ’low risk’ or ‘high risk of bias’ for selective reporting for any of the 43 studies.

Other potential sources of bias Treatment and control groups were comparable at entry in 35 studies (’low risk of bias’), it was unclear in six studies (’unclear risk of bias’) (Bergstrom 2008; Brentano 2008; Grove 1992; Metcalfe 2001; Newstead 2004; Sinaki 1989) and significant differences were present in two studies indicating a ’high risk of bias’ (Prince 1991; Rubin 2004). Most studies only provided data at the end of the intervention. Only eight studies provided follow-up data (Englund 2005; Karinkanta 2007; Korpelainen 2006; Metcalfe 2001; Preisinger 1995; Prince 1991; Revel 1993; Uusi-Rasi 2003).

and 1441 participants (Analysis 1.2); and trochanter (MD 1.03; 95% CI 0.56 to 1.49), 10 studies and 815 participants (Analysis 1.6). The risk of fracture in exercise groups was not significantly different than that in controls (OR 0.61; 95% CI 0.23 to 1.64), four studies and 539 participants. There was no significant difference between the exercise and control groups for: percentage change in BMD at the femoral neck (MD -0.08; 95% CI -1.08 to 0.92), 19 studies and 1338 participants; or total hip (MD 0.41; 95% CI 0.64 to 1.45), 13 studies and 863 participants. Only one study (Uusi-Rasi 2003), 76 participants, reported percentage change in BMC for the spine and femoral neck and no significant differences were observed between the exercise and control groups. Three studies (Chan 2004; Ebrahim 1997; Karinkanta 2007) (n = 378) reported falls as adverse events. There were 75 falls reported in the exercise groups and 55 in the control groups. Other adverse events were reported in 11 studies (Chow 1987; Ebrahim 1997; Grove 1992; Karinkanta 2007; Korpelainen 2006; Nelson 1994; Pruitt 1996; Revel 1993; Rubin 2004; Russo 2003; Uusi-Rasi 2003); 60 events were reported in the exercise groups and five in the control groups, and included muscle soreness, joint pain, headache and itching. 2. Static weight bearing (SWB) (Analysis 2.1)

See: Summary of findings for the main comparison Exercise for preventing and treating osteoporosis in postmenopausal women

Only one study Sakai 2010 involving 31 participants examined SWB (standing on one leg for three minutes per day). A significant difference was reported for percentage change in BMD at the hip (Analysis 2.1).

1. All exercise types versus control (Analyses 1.1 to 1.8)

3. Dynamic weight bearing exercise low force (DWBLF) (Analyses 3.1 to 3.7)

Effects of interventions

Thirty-one studies examining exercise programmes versus control reported data for the seven outcomes selected as important to decision making: • total number of fractures; • percentage change in BMD at the spine; • percentage change in BMD at the femoral neck; • percentage change in BMD in total hip; • percentage change in BMD at the trochanter; • adverse events (falls); and • other adverse events (muscle soreness, joint pain, headache and itching). These results are reported in Summary of findings for the main comparison. However, the nature of the exercise programmes were heterogeneous and thus the results should be considered with caution. Among these studies 13 were considered to have ’low risk of bias’. Meta-analyses revealed significant differences between the exercise and control groups in favour of exercise for percentage change in BMD at the spine (MD 0.85; 95% CI 0.62 to 1.07), 24 studies

Nine studies examining DWBLF exercise (including walking and Tai chi) reported data on 705 participants. Among these studies five were considered to have ’low risk of bias’ (Bravo 1996; Chow 1987; Ebrahim 1997; Lau 1992; Lord 1996). The compliance with exercise programmes, when reported, varied from 39% (Prince 1995) to 79.2% (Martin 1993). The results of meta-analysis showed that there was a statistically significant effect on percentage change in BMD of the spine (MD 0.87; 95% CI 0.26 to 1.48), seven studies and 1119 participants (Analysis 3.1), in favour of exercise. However there was no effect on the femoral neck (MD -1.20; 95% CI -4.45 to 2.05), five studies and 585 participants; trochanter (MD 0.39; 95% CI -0.59 to 1.38), two studies and 241 participants; or number of fractures (OR 0.92; 95% CI 0.21 to 3.96), two studies and 229 participants. Results of single studies indicate a significant difference in favour of exercise for percentage change of mean regression slope in BMD at the wrist (MD 1.40; 95% CI 0.85 to 1.95), 103 participants (Preisinger 1995), and in favour of the control group for percentage change in BMD in Ward’s triangle (MD -3.60; 95% CI -5.48 to -1.72), 23 participants (Lau 1992).

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4. Dynamic weight bearing exercise high force (DWBHF) (Analyses 4.1 to 4.16) Ten studies examining DWBHF exercise (including jogging, jumping, running, dancing and vibration platform) reported data on 568 participants. Among these studies four were considered to have ’low risk of bias’ (Cheng 2002; Karinkanta 2007; Uusi-Rasi 2003; Verschueren 2004). The compliance with exercise programmes, when reported, varied from 82.6% (Grove 1992) to 86.2% (Maddalozzo 2007). The results of meta-analysis showed that there was a statistically significant effect on percentage change in BMD of the hip (MD 1.55; 95% CI 1.41 to 1.69), four studies and 179 participants (Analysis 4.2); and trochanter (MD 1.23; 95% CI -0.01 to 2.47), two studies and 188 participants (Analysis 4.6) in favour of exercise. There was no effect on the percentage change in BMD of the spine (MD -1.20; 95% CI -4.45 to 2.05); mid femur (MD 0.12; 95% CI -4.84 to 5.08); proximal tibia (MD 3.31; 95% CI -20.22 to 26.84); femoral neck (MD 1.06; 95% CI -0.32 to 2.45); or on CaBI at the trunk and upper thighs (MD 5.30; 95% CI -7.50 to 18.10). Results of a single study (Uusi-Rasi 2003) with 76 participants did not indicate any effect on percentage change in BMC at the spine (MD 1.43; 95% CI -9.18 to 12.04); femoral neck (MD 0.00; 95% CI -9.11 to 9.11); or wrist (MD -3.41; 95% CI -15.64 to 8.82).

5. Non-weight bearing exercise low force (NWBLF) (Analyses 5.1 to 5.6) Five of six studies examining NWBLF exercise (e.g. low load, high repetition strength training) reported data on 231 participants. Among these studies none were considered to have ’low risk of bias’. The compliance with exercise programmes, when reported, varied from 65% (Pruitt 1996) to 90% (Kerr 2001). No significant differences were observed for any outcome.

6. Non-weight bearing exercise high force (NWBHF) (Analayses 6.1 to 6.6) Nine studies examining NWBHF exercise (e.g. progressive resisted strengthening exercise) reported data on 292 participants. Among these studies one was considered to have ’low risk of bias’ (Chilibeck 2002). The compliance with exercise programmes, when reported, varied from 65% (Pruitt 1996) to 92% (Kerr 2001). The results of meta-analysis showed that there was a statistically significant effect on percentage change in BMD of the spine (MD 0.86; 95% CI 0.58 to 1.13), eight studies and 246 participants ( Analysis 6.1); and neck of femur (MD 1.03; 95% CI 0.24 to 1.82), eight studies and 247 participants (Analysis 6.3). No significant differences were observed for any other outcome.

7. Combination (COMB) (Analyses 7.1 to 7.9) Ten studies examining combinations of exercise types (more than one of the above exercise interventions) reported data on 823 participants. Among these studies five were considered to have ’low risk of bias’ (Bergstrom 2008; Chow 1987; Chubak 2006; Karinkanta 2007; Korpelainen 2006). The compliance with exercise programmes, when reported, varied from 62% (Papaioannou 2003) to 95% (Bergstrom 2008). The results of meta-analysis showed that the risk of fractures in exercise groups was significantly lower than that in controls (OR 0.33; 95% CI 0.13 to 0.85), two studies and 236 participants (Analysis 7.9): in percentage change in BMD of the spine (MD 3.22; 95% CI 1.80 to 4.64), four studies and 258 participants (Analysis 7.1); trochanter (MD 1.31; 95% CI 0.69 to 1.92), two studies and 200 participants (Analysis 7.3); and neck of femur (MD 0.45; 95% CI 0.08 to 0.82), three studies and 325 participants (Analysis 7.6). However the results of meta-analysis showed that there was a statistically significant effect in favour of control in percentage change in BMD of the total hip (MD -1.07; 95% CI -1.58 to -0.56), four studies and 468 participants (Analysis 7.2).

8. Exercise and pharmacological products versus control and pharmacological products (Analyses 8.1 to 15.2) Ten studies examining exercise and pharmacological products versus control and pharmacological products reported data on 598 participants. Among these studies four were considered to have ’low risk of bias’. The pharmacological products were hormone replacement therapy (HRT) (Cheng 2002; Maddalozzo 2007; Going 2003), bisphosphonates (Chilibeck 2002; Iwamoto 2005; Uusi-Rasi 2003), antioxidants (Chuin 2009), calcium (Kerr 2001; Lau 1992; Prince 1995) and calcium plus vitamin D (Martin 1993). Exercise types included DWBHF (Cheng 2002; Going 2003; Iwamoto 2005; Maddalozzo 2007; Uusi-Rasi 2003), DWBLF and NWBLF (Kerr 2001), and NWBHF (Chilibeck 2002; Chuin 2009; Kerr 2001). Compliance with exercise programmes, when reported, varied from 39% (Prince 1995) to 92% (Kerr 2001). On the whole data for these eight comparisons comprised small single studies. DWBHF plus HRT versus HRT demonstrated a significant effect in favour of exercise in percentage change in BMD at the trochanter (MD 1.86; 95% CI 0.60 to 3.13), 2 studies and 203 participants; spine NWBHF plus bisphosphonates versus bisphosphonates (Chilibeck 2002), 26 participants; distal tibia and Ward’s triangle DWBLF plus calcium versus calcium (MD 0.60; 95% CI 0.46 to 0.74) (Prince 1995) and (MD 14.50; 95% CI 10.05 to 18.95) (Lau 1992). However a significant difference in favour of calcium was seen for DWBLF plus calcium versus calcium (MD -1.02; 95% CI -1.36 to -0.68) (Lau 1992).

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No significant differences were observed for any outcome for any exercise type and pharmacological products versus control and pharmacological products as listed above.

DISCUSSION

Summary of main results We have summarised the data from 43 RCTs comparing exercise with usual activity and exercise plus pharmacological products versus pharmacological products. We also separately examined the effect of different categories of exercise. Our results suggest a relatively small statistically significant, but possibly important, effect of exercise on bone density in postmenopausal women compared with control groups. The risk of fracture in exercise groups was not significantly different than that in controls (OR 0.61; 95% CI 0.23 to 1.64). Our inference is strengthened by the consistency of significant findings in favour of exercise for percentage change in BMD across three sites; spine (MD 0.85; 95% CI 0.62 to 1.07); total hip (MD 0.41; 95% CI 0.64 to 1.45); and trochanter (MD 1.03; 95% CI 0.56 to 1.49). This inference is, however, weakened by methodological limitations such as small sample sizes, loss to follow-up in most studies and by the unexplained heterogeneity of results across studies. Few studies provided follow-up data to determine the effect of exercise beyond the end of the intervention. Falls were reported as adverse events as numbers of falls rather than number of fallers; one study reported more events than people, indicating repeat falls. Other adverse events were reported for participants mainly in intervention groups and included muscle soreness, joint pain, headache and itching. There was generally no mention of event monitoring in control groups. COMB exercise programmes (comprising more than one exercise type) had a significant effect on BMD at three sites: neck of femur; spine; and trochanter. The risk of fracture in exercise groups was lower than that of controls. However there was a significant difference in BMD in total hip measurement in favour of the control group. DWBHF exercise (jogging, jumping and vibration platforms) had a significant effect on BMD at two sites; total hip and trochanter, compared to the control groups, but no effect at any other site (neck of femur, spine, mid femur, tibia, trunk and thighs, or BMC at neck of femur and spine). DWBLF exercise (walking or Tai chi) had a significant effect on BMD at two sites; spine and wrist compared to the control groups. NWBHF exercise (progressive resistance exercise) had a significant effect on BMD at two sites; neck of femur and spine compared to the control groups. SWB exercise (e.g. single leg standing) had a significant effect on BMD at the hip.

NWBLF exercise (low load high repetition strength training) had no significant difference on any outcomes reported. On the whole, comparisons of exercise plus pharmacological products versus pharmacological products were small single studies and thus conclusions on their findings are limited. The population included in these studies was heterogeneous but results should be reviewed with caution due to differences in ethnicity. However, the lack of reporting of exercise characteristics (type, intensity, frequency, duration and mode) of the study exercise interventions also limits the conclusions that can be drawn from this review.

Overall completeness and applicability of evidence It is important for future research in this area to have standardised recommendations for conducting exercise interventions and reporting of exercise outcomes. We cannot currently determine if the effect of the varied exercises was different in the first and in the second period of the postmenopausal time period. The short time of the follow-up of all the studies limits our ability to predict the long-term effects exercise may or may not have on bone loss.

Quality of the evidence The 43 studies (27 new studies in this update) included in this review were predominantly in the English language and originate mainly from North America and Europe (n = 32). Whilst this may be seen to limit the applicability of the evidence to these healthcare systems and social environments the evidence has potential generalisability; the majority of participants were healthy communitydwelling women. The overall quality of the included studies was variable and should be taken into account when interpreting the results of this review. The risk of bias was assessed as ’low’ for only 13 studies (Bergstrom 2008; Bravo 1996; Cheng 2002; Chilibeck 2002; Chow 1987; Chubak 2006; Ebrahim 1997; Karinkanta 2007; Korpelainen 2006; Lau 1992; Lord 1996; Uusi-Rasi 2003; Verschueren 2004). Only one study included in this review blinded the patients ( Rubin 2004) and few blinded the assessors (Bocalini 2009; Bravo 1996; Chilibeck 2002; Chow 1987; Chubak 2006; Hatori 1993; Korpelainen 2006; Papaioannou 2003; Preisinger 1995; Revel 1993; Rubin 2004; Sinaki 1989; Uusi-Rasi 2003; Verschueren 2004). It is very difficult and maybe impossible to blind patients and care providers in exercise therapy. Nevertheless, this bias is unlikely to have influenced the BMD measurements.

Potential biases in the review process

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The review was restricted to RCTs; we excluded clinical controlled trials CCTs) thus limiting the potential for bias. All studies described themselves as randomised mostly without giving details of how the randomisation sequence was generated and what precautions were taken in relation to concealment of allocation. Only eight studies adequately deal with incomplete outcome data (Englund 2005; Karinkanta 2007; Korpelainen 2006; Metcalfe 2001; Preisinger 1995; Prince 1991; Revel 1993; Uusi-Rasi 2003) the remainder reporting the results for only those participants who completed all post-treatment assessments. Fractures, falls and other adverse events were reported as adverse events and were mainly monitored for the exercise groups only.

Agreements and disagreements with other studies or reviews Few meta-analyses have been published in this area (Berard 1997; Hind 2007; Wolff 1999). These meta-analyses included RCTs and CCTs, one (Wolff 1999) also included studies on premenopausal women. All authors subdivided the studies depending on the exercise characteristics and meta-analysed all exercise programmes together. While Wolff 1999 concluded that exercises prevent femoral and lumbar bone loss, Berard 1997 concluded that weight bearing exercises are effective mainly on the spine, but there may be some evidence of efficacy on femoral bone and forearm bone. Weight bearing exercise also appears to enhance bone mineral accrual in children, particularly during early puberty (Hind 2007). The results of a meta-analysis in Nikander 2010 indicate that exercise can significantly enhance bone strength at loaded sites in children but not in adults. Other reviews with limited quality evidence suggest that Tai chi (Wayne 2007) and physical activity (Schmitt 2009) may be effective and safe methods of maintaining BMD in postmenopausal women. Furthermore an overview of the literature (Winett 2001) purports the benefits of resistance training on BMD. The results of this current review suggest that high force resistance training increases BMD whereas low force does not, indicating the importance of intensity of exercise. This current review reported on bone mass as an outcome of effectiveness and included BMC, CaBI and BMD. Zebaze 2010 reported that most bone loss is cortical, not trabecular, and occurs after 65 years of age, and the resulting structural decay, including the magnitude of intracortical remodelling and intracortical porosity are poorly captured by current measurement methods. Nikander 2010 recommends that further research is required to quantify the effects of exercise on whole bone strength and its structural determinants throughout life.

AUTHORS’ CONCLUSIONS Implications for practice Our results suggest a relatively small statistically significant, but possibly important, effect of exercise on bone density in postmenopausal women compared with control groups. The most effective type of exercise intervention on BMD for the neck of femur appears to be NWBHF exercise such as progressive resistance strength training for the lower limbs. The most effective intervention for BMD at the spine was COMB exercise programmes (comprising more than one exercise type) (MD 3.22; 95% CI 1.80 to 4.64), with a change of over 3% compared with control groups. However the risk of fracture across all exercise groups was not significantly different than that in controls with 4 more women out of 100 who did not exercise sustaining a fracture (absolute difference 4%). These exercise types should be considered as preferred interventions in clinical practice, however, it remains unclear as to what constitutes an optimal exercise programme.

Implications for research On the whole the quality of the reporting of studies in the metaanalyses in this review was low, in particular in the areas of sequence generation, allocation concealment, blinding and loss to follow-up. Future research needs to focus on standardised outcome measures and exercise programmes, better reporting of all the parameters of exercise programmes and, the accuracy of measurements. Fracture and fall data, and adverse event reporting for all participants regardless of group allocation should be included for all future studies. Measuring the BMD changes for both the hip (particularly neck of femur) and spine is important as fractures at these sites result in high mortality and morbidity. Adequate follow-up of participants is required to determine long-term effects of exercise.

ACKNOWLEDGEMENTS We would like to acknowledge the following for their contribution to the original systematic review: Donatella Bonaituti, Lovine R, Negrini S, Welch V, Kemper HHCG, Wells GA, Tugwell P, Cranney A. We would also like to thank Louise Falzon and Tamara Rader for their assistance with the literature search. A special thanks to Jon Godwin for his helpful advice on data queries, comments and suggestions, Sarah Mitchell for assistance with data extraction and to Elizabeth Ghogomu and the Cochrane Musculoskeletal Group for their ongoing support and their help with the preparation of this manuscript.

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REFERENCES

References to studies included in this review Bemben 2000 {published data only} Bemben DA, Fetters NL, Bemben MG, Nabavi N, Koh ET. Musculoskeletal responses to high- and low-intensity resistance training in early postmenopausal women. Medicine and Science in Sports and Exercise 2000;32(11): 1949–57. Bergstrom 2008 {published data only} Bergstrom I, Landgren B, Brinck J, Freyschuss B. Physical training preserves bone mineral density in postmenopausal women with forearm fractures and low bone mineral density. Osteoporosis International 2008;19(2):177–83. Bocalini 2009 {published data only} Bocalini DS, Serra AJ, Dos Santos L, Murad N, Levy RF. Strength training preserves the bone mineral density of postmenopausal women without hormone replacement therapy. Journal of Aging and Health 2009;21(3):519–27. Bravo 1996 {published data only} Bravo G, Gauthier P, Roy PM, Payette H, Gaulin P, Harvey M, et al.Impact of a 12-month exercise program on the physical and psychological health of osteopenic women. Journal of the American Geriatrics Society 1996;44(7): 756–762. Brentano 2008 {published data only} Brentano Cadore EL, Da Silva EM, Ambrosini AB, Coertjens M, Petkowicz R, Viero I, et al.National Strength and Conditioning Association. Physiological adaptations to strength and circuit training in postmenopausal women with bone loss. Journal of Strength and Conditioning Research 2008;22(6):1816–25. Chan 2004 {published data only} Chan K, Qin L, Lau M, Woo J, Au S, Choy W, et al.A randomized, prospective study of the effects of Tai Chi Chun exercise on bone mineral density in postmenopausal women. Archives of Physical Medicine and Rehabilitation 2004;85(5):717–22. Cheng 2002 {published data only} Cheng S, Sipila S, Taaffe DR, Puolakka J, Suominen H. Change in bone mass distribution induced by hormone replacement therapy and high-impact physical exercise in post-menopausal women. Bone 2002;31(1):126–35. Chilibeck 2002 {published data only} Chilibeck PD, Davison KS, Whiting SJ, Suzuki Y, Janzen CL, Peloso P. The effect of strength training combined with bisphosphonate (etidronate) therapy on bone mineral, lean tissue, and fat mass in postmenopausal women. Canadian Journal of Physiology and Pharmacology 2002;80(10): 941–50. Chow 1987 {published data only} Chow R, Harrison JE, Notarius C. Effect of two randomised exercise programmes on bone mass of healthy postmenopausal women. British Medical Journal 1987;295: 1441–4.

Chubak 2006 {published data only} Chubak J, Ulrich CM, Tworoger SS, Sorensen B, Yasui Y, Irwin ML, et al.Effect of exercise on bone mineral density and lean mass in postmenopausal women. Medicine and Science in Sports and Exercise 2006;38(7):1236–44. Chuin 2009 {published data only} Chuin A, Labonte M, Tessier D, Khalil A, Bobeuf F, Doyon CY, et al.Effect of antioxidants combined to resistance training on BMD in elderly women: A pilot study. Osteoporosis International 2009;20(7):1253–8. Ebrahim 1997 {published data only} Ebrahim S, Thompson PW, Baskaran V, Evans K. Randomized placebo-controlled trial of brisk walking in the prevention of postmenopausal osteoporosis. Age and Aging 1997;26(4):253–260. Englund 2005 {published data only} Englund U, Littbrand H, Sondell A, Bucht G, Pettersson U. The beneficial effects of exercise on BMD are lost after cessation: a 5-year follow-up in older post-menopausal women. Scandinavian Journal of Medicine and Science in Sports 2009;19(3):381–8. ∗ Englund U, Littbrand H, Sondell A, Pettersson U, Bucht G. A 1-year combined weight-bearing training program is beneficial for bone mineral density and neuromuscular function in older women. Osteoporosis International 2005; 16(9):1117–23. Going 2003 {published data only} Going S, Lohman T, Houtkooper L, Metcalfe L, FlintWagner H, Blew R, et al.Effects of exercise on bone mineral density in calcium-replete postmenopausal women with and without hormone replacement therapy. Osteoporosis International 2003;14(8):637–43. Grove 1992 {published data only} Grove KA, Londeree BR. Bone density in postmenopausal women: high impact vs low impact exercise. Medicine and Science in Sports and Exercise 1992;24(11):1190–4. Hatori 1993 {published data only} Hatori M, Hasegawa A, Adachi H, Shinozaki A, Hayashi R, Okano H, et al.The effects of walking at the anaerobic threshold level on vertebral bone loss in postmenopausal women. Calcified Tissue International 1993;52:411–14. Iwamoto 2001 {published data only} Iwamoto J, Takeda T, Ichimura S. Effect of exercise training and detraining on bone mineral density in postmenopausal women with osteoporosis. Journal of Orthopaedic Science 2001;6(2):128–32. Iwamoto 2005 {published data only} Iwamoto J, Takeda T, Sato Y, Uzawa M. Effect of wholebody vibration exercise on lumbar bone mineral density, bone turnover, and chronic back pain in post-menopausal osteoporotic women treated with alendronate. AgingClinical and Experimental Research 2005;17(2):157–63.

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Karinkanta 2007 {published data only} Karinkanta S, Heinonen A, Sievanen H, Uusi-Rasi K, Fogelholm M, Kannus P. Maintenance of exercise-induced benefits in physical functioning and bone among elderly women. Osteoporosis International 2009;20(4):665–74. ∗ Karinkanta S, Heinonen A, Sievanen H, UusiRasi K, Pasanen M, Ojala K, et al.European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. A multi-component exercise regimen to prevent functional decline and bone fragility in home-dwelling elderly women: randomized, controlled trial. Osteoporosis International 2007;18(4):453–62. Kerr 2001 {published data only} Kerr D, Ackland T, Maslen B, Morton A, Prince R. Resistance training over 2 years increases bone mass in calcium-replete postmenopausal women. Journal of Bone and Mineral Research 2001;16(1):175–81. Korpelainen 2006 {published data only} ∗ Keinanen-Kiukaanniemi S, Heikkinen J, Vaananen K, Korpelainen J. Effect of impact exercise on bone mineral density in elderly women with low BMD: a populationbased randomized controlled 30-month intervention. Osteoporosis International 2006;17(1):109–18. Korpelainen R, Keinanen-Kiukaanniemi S, Nieminen P, Heikkinen J, Vaananen K, Korpelainen J. Long-term outcomes of exercise: follow-up of a randomized trial in older women with osteopenia. Archives of Internal Medicine 2010;170(17):1548–56. Lau 1992 {published data only} Lau EMC, Woo J, Leung PC, Swaminathan R, Leung D. The effects of calcium supplementation and exercise on bone density in elderly Chinese women. Osteoporosis International 1992;2(4):168–73. Lord 1996 {published data only} Lord SR, Ward JA, Williams P, Zivanovic E. The effects of a community exercise program on fracture risk factors in older women. Osteoporosis International 1996;6(5):361–7. Maddalozzo 2007 {published data only} Maddalozzo GF, Widrick JJ, Cardinal BJ, Winters-Stone KM, Hoffman MA, Snow CM. The effects of hormone replacement therapy and resistance training on spine bone mineral density in early postmenopausal women. Bone 2007;40(5):1244–51. Martin 1993 {published data only} Martin D, Notelovitz M. Effects of aerobic training on bone mineral density of postmenopausal women. Journal of Bone and Mineral Research 1993;8(8):931–6. Metcalfe 2001 {published data only} Houtkooper LB, Stanford VA, Metcalfe LL, Lohman TG, Going SB. Preventing osteoporosis the bone estrogen strength training way. ACSM’s Health and Fitness Journal 2007;11(1):21. Metcalfe L. The BEST exercise program for osteoporosis prevention. Functional U 2007;5(2):1. ∗ Metcalfe L, Lohman T, Going S, Houtkooper L, Ferriera D, Flint-Wagner H, et al.Postmenopausal women and

exercise for prevention of osteoporosis: the Bone, Estrogen, Strength Training (BEST) study. ACSM’s Health & Fitness Journal 2001;5(3):6. Nelson 1994 {published data only} Nelson ME, Fiatarone MA, Morganti CM, Trice I, Greenberg RA, Evans WJ. Effects of high-intensity strength training on multiple risk factors for osteoporotic fractures. JAMA 1994;272(24):1909–14. Newstead 2004 {published data only} Newstead A, Smith KI, Bruder J, Keller C. The effect of a jumping exercise intervention on bone mineral density in postmenopausal women. Journal of Geriatric Physical Therapy 2004;27(2):47–52. Papaioannou 2003 {published data only} ∗ Papaioannou A, Adachi JD, Winegard K, Ferko N, Parkinson W, Cook RJ, et al.Efficacy of home-based exercise for improving quality of life among elderly women with symptomatic osteoporosis-related vertebral fractures. Osteoporosis International 2003;14(8):677–82. Webber CE, Papaioannou A, Winegard KJ, Adachi JD, Parkinson W, Ferko NC, et al.A 6-mo home-based exercise program may slow vertebral height loss. Journal of Clinical Densitometry 2003;6(4):391–400. Preisinger 1995 {published data only} ∗ Preisinger E, Alacamlioglu Y, Pils K, Saradeth T, Schneider B. Therapeutic exercise in the prevention of bone loss. A controlled trial with women after menopause. American Journal of Physical Medicine and Rehabilitation 1995;74(2): 120–3. Preisinger E, Kerschan-Schindl K, Wober C, Kollmitzer J, Ebenbichler G, Hamwi A, et al.The effect of calisthenic home exercises on postmenopausal fractures-a long-term observational study. Maturitas 2001;40(1):61–7. Prince 1991 {published data only} Prince RL, Smith M, Dick IM, Price RI, Webb PG, Henderson NK, et al.Prevention of postmenopausal osteoporosis: a comparative study of exercise, calcium supplementation, and hormone-replacement therapy. New England Journal of Medicine 1991;325(17):1189–95. Prince 1995 {published data only} Prince R, Devine A, Dick I, Criddle A, Kerr D, Kent N, et al.The effects of calcium supplementation (milk powder or tablets) and exercise on one ensity in postmenopausal women. Journal of Bone and Mineral Research 1995;10(7): 1068–75. Pruitt 1996 {published data only} Pruitt LA, Taaffe DR, Marcus R. Effects of a one-year highintensity versus low-intensity resistance training program on bone mineral density in older women. Journal of Bone and Mineral Research 1996;10(11):1788–95. Revel 1993 {published data only} Mayoux-Benhamou MA, Bagheri F, Roux C, Auleley GR, Rabourdin JP, Revel M. Effect of Ppsoas training on

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postmenopausal lumbar bone loss: a 3-year follow-up study. Calcified Tissue International 1997;60(4):348–53. ∗ Revel M, Mayoux-Benhamou MA, Rabourdin JP, Bagheri F, Roux C. One-year psoas training can prevent lumbar bone loss in postmenopausal women: a randomized controlled trial. Calcified Tissue International 1993;53(5):307–11. Rubin 2004 {published data only} Rubin C, Recker R, Cullen D, Ryaby J, McCabe J, McLeod K. Prevention of postmenopausal bone loss by a lowmagnitude, high-frequency mechanical stimuli: a clinical trial assessing compliance, efficacy, and safety. Journal of Bone and Mineral Research 2004;19(3):343–51. Russo 2003 {published data only} Russo CR, Lauretani F, Bandinelli S, Bartali B, Cavazzini C, Guralnik JM, et al.High-frequency vibration training increases muscle power in postmenopausal women. Archives of Physical Medicine and Rehabilitation 2003;84(12): 1854–7. Sakai 2010 {published data only} Sakai A, Oshige T, Zenke Y, Yamanaka Y, Nagaishi H, Nakamura T. Unipedal standing exercise and hip bone mineral density in postmenopausal women: a randomized controlled trial. Journal of Bone and Mineral Metabolism 2010;28(1):42–8. Sinaki 1989 {published data only} Sinaki M, Wahner HW, Offord KP, Hodgson SF. Efficacy of nonloading exercises in prevention of vertebral bone loss in postmenopausal women: a controlled trial. Mayo Clinic Proceedings 1989;64(7):762–9. Smidt 1992 {published data only} Smidt GL, Lin SY, O’Dwyer KD, Blanpied PR. The effect of high-intensity trunk exercise on bone mineral density of postmenopausal women. Spine 1992;17(3):280. Tolomio 2009 {published data only} Tolomio S, Lalli A, Travain G, Zaccaria M. Effects of a combined weight- and non weight-bearing (water) exercise program on bone mass and quality in postmenopausal women with low bone mineral density. Clinica Terapeutica 2009;160(2):105–9. Uusi-Rasi 2003 {published data only} ∗ Uusi-Rasi K, Kannus P, Cheng S, Sievanen H, Pasanen M, Heinonen A, et al.Effect of alendronate and exercise on bone and physical performance of postmenopausal women: A randomized controlled trial. Bone 2003;33(1):132–43. Uusi-Rasi K, Sievanen H, Heinonen A, Kannus P, Vuori I. Effect of discontinuation of alendronate treatment and exercise on bone mass and physical fitness: 15-month follow-up of a randomized, controlled trial. Bone 2004;35 (3):799–805. Verschueren 2004 {published data only} Verschueren SM, Roelants M, Delecluse C, Swinnen S, Vanderschueren D, Boonen S. Effect of 6-month whole body vibration training on hip density, muscle strength, and postural control in postmenopausal women: a randomized controlled pilot study. Journal of Bone and Mineral Research 2004;19(3):352–9.

Von Stengel 2009 {published data only} Von Stengel S, Kemmler W, Mayer S, Engelke K, Klarner A, Kalender WA. Effect of whole body vibration exercise on osteoporotic risk factors. Deutsche Medizinische Wochenschrift (1946) 2009;134(30):1511–6.

References to studies excluded from this review Ay 2005 {published data only} Ay A, Yurtkuran M. Influence of aquatic and weightbearing exercises on quantitative ultrasound variables in postmenopausal women. American Journal of Physical Medicine and Rehabilitation 2005;84(1):52–61. Bebenek 2010 {published data only} Bebenek M, Kemmler W, Von Stengel S, Engelke K, Kalender WA. Effect of exercise and Cimicifuga racemosa (CR BNO 1055) on bone mineral density, 10-year coronary heart disease risk, and menopausal complaints: the randomized controlled Training and Cimicifuga racemosa Erlangen (TRACE) study. Menopause (10723714) 2010;17 (4):791–800. Bemben 2010 {published data only} Bemben DA, Palmer IJ, Bemben MG, Knehans AW. Effects of combined whole-body vibration and resistance training on muscular strength and bone metabolism in postmenopausal women. Bone 2010;47(3):650–6. Cao 2009 {published data only} Cao ZB, Tabata I, Nishizono H. Good maintenance of physical benefits in a 12-month exercise and nutritional intervention by voluntary, home-based exercise: a 6-month follow-up of a randomized controlled trial. Journal of Bone and Mineral Metabolism 2009;27(2):182–9. De Matos 2009 {published data only} De Matos O, Da Silva DJL, De Oliveira JM, CasteloBranco C. Effect of specific exercise training on bone mineral density in women with postmenopausal osteopenia or osteoporosis. Gynecological Endocrinology 2009;25(9): 616–20. Engelke 2006 {published data only} Engelke K, Kemmler W, Lauber D, Beeskow C, Pintag R, Kalender WA. Exercise maintains bone density at spine and hip EFOPS: a 3-year longitudinal study in early postmenopausal women. Osteoporosis International 2006;17 (1):133–42. Hans 2002 {published data only} Hans D, Genton L, Drezner MK, Schott AM, Pacifici R, Avioli L, et al.Monitored impact loading of the hip: initial testing of a home-use device. Calcified Tissue International 2002;71(2):112–20. Hawkins 2002 {published data only} Hawkins SA, Wiswell RA, Schroeder ET. The relationship between bone adaptations to resistance exercise and reproductive-hormone levels. Journal of Aging and Physical Activity 2002;10(1):64–75. Heinonen 1996 {published data only} Heinonen A, Kannus P, Sievanen H, Oja P, Pasanen M, Rinne M, et al.Randomised controlled trial of effect of

Exercise for preventing and treating osteoporosis in postmenopausal women (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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high-impact exercise on selected risk factors for osteoporotic fractures. Lancet 1996;348(9038):1343–7.

randomized prospective study. Journal of Bone and Mineral Research 1995;10(7):1015–24.

Kemmler 2003 {published data only} ∗ Kemmler W, Engelke K, Weineck J, Hensen J, Kalender WA. The Erlangen Fitness Osteoporosis Prevention Study: a controlled exercise trial in early postmenopausal women with low bone density - first-year results. Archives of Physical Medicine and Rehabilitation 2003;84(5):673–82. Kemmler W, Lauber D, Weineck J, Hensen J, Kalender W, Engelke K. Benefits of 2 years of intense exercise on bone density, physical fitness, and blood lipids in early postmenopausal osteopenic women: Results of the Erlangen Fitness Osteoporosis Prevention Study (EFOPS). Archives of Internal Medicine 2004;164(10):1084–91. Kemmler W, Von Stengel S, Weineck J, Lauber D, Kalender W, Engelke K. Exercise effects on menopausal risk factors of early postmenopausal women: 3-Yr erlangen fitness osteoporosis prevention study results. Medicine and Science in Sports and Exercise 2005;37(2):194–203.

Mayoux-Benhamou 1995 {published data only} Mayoux-Benhamou MA, Rabourdin JP, Bagheri F, Roux C, Revel M. Effet de l’exercice physique sur la densité osseuse lombaire chez la femme ménopausée. Ann Readaptation Med Phys 1995;38:117–124.

Kerr 1996 {published data only} Kerr D, Morton A, Dick I, Prince R. Exercise effects on bone mass in postmenopausal women are site-specific and load-dependent. Journal of Bone and Mineral Research 1996; 11(2):218–25.

Pruitt 1992 {published data only} Pruitt LA, Jackson RD, Bartels RL, Lehnhard HL. Weight-training effects on bone mineral density in early postmenopausal women. Journal of Bone and Mineral Research 1992;7(2):179–85.

Kerschan-Schindl 2000 {published data only} Kerschan-Schindl K, Uher E, Kainberger F, Kaider A, Ghanem AH, Preisinger E. Long-term home exercise program: Effect in women at high risk of fracture. Archives of Physical Medicine and Rehabilitation 2000;81(3):319–23.

Rikli 1990 {published data only} Rikli RE, McManis BG. Effects of exercise on bone mineral content in postmenopausal women. Research Quarterly for Exercise and Sport 1990;61(3):243–9.

Kohrt 1995 {published data only} Kohrt WM, Snead DB, Slatopolsky E, Birge S. Additive effects of weight-bearing exercise and estrogen on bone mineral density in older women. Journal of Bone and Mineral Research 1995;10(9):1303–11. Kontulainen 2004 {published data only} Kontulainen S, Heinonen A, Kannus P, Pasanen M, Sievanen H, Vuori I. Former exercisers of an 18-month intervention display residual aBMD benefits compared with control women 3.5 years post-intervention: a follow-up of a randomized controlled high-impact trial. Osteoporosis International 2004;15(3):248–51. Kriska 1986 {published data only} Kriska AM, Bayles C, Cauley JA, Laporte RE, Sandler RB, Pambianco G. A randomized exercise trial in older women: increased activity over two years and the factors associated with compliance. Medicine and Science in Sports and Exercise 1986;18(5):557–62. Leichter 1989 {published data only} Leichter I, Simkin A, Margulies JY, Bivas A, Steinberg R, Giladi M, et al.Gain in mass density of bone following strenuous physical activity. Journal of Orthopaedic Research 1989;7(1):86–90. Lohman 1995 {published data only} Lohman T, Going S, Pamenter R, Hall M, Boyden T, Houtkooper L, et al.Effects of resistance training on regional and total bone mineral density in premenopausal women: a

Nelson 1991 {published data only} Nelson ME, Fisher EC, Dilmanian FA, Dallal GE, Evans WJ. A 1-year walking program and increased dietary calcium in postmenopausal women: effects on bone. American Journal of Clinical Nutrition 1991;53(5):1304–11. Notelovitz 1991 {published data only} Notelovitz M, Martin D, Tesar R, Khan FY, Probart C, Fields C, et al.Estrogen therapy and variable-resistance weight training increase bone mineral in surgically menopausal women. Journal of Bone and Mineral Research 1991;6(6):583–4.

Ruan 2008 {published data only} Ruan XY, Jin FY, Liu YL, Peng ZL, Sun YG. Effects of vibration therapy on bone mineral density in postmenopausal women with osteoporosis. Chinese Medical Journal 2008;121(13):1155–8. Shen 2009 {published data only} Shen CL, Chyu MC, Yeh JK, Felton CK, Xu KT, Pence BC, et al.Green tea polyphenols and Tai Chi for bone health: designing a placebo-controlled randomized trial. BMC Musculoskeletal Disorders 2009;10:110. Snow 2000 {published data only} Snow CM, Shaw JM, Winters KM, Witzke KA. Longterm exercise using weighted vests prevents hip bone loss in postmenopausal women. Journals of Gerontology - Series A Biological Sciences and Medical Sciences 2000;55(9): M489–91. Song 2010 {published data only} Song R, Roberts BL, Lee E, Lam P, Bae S. A randomized study of the effects of t’ai chi on muscle strength, bone mineral density, and fear of falling in women with osteoarthritis. Journal of Alternative and Complementary Medicine 2010;16(3):227–33. Tolomio 2008 {published data only} Tolomio S, Ermolao A, Travain G, Zacearia M. Short-term adapted physical activity program improves bone quality in osteopenic/osteoporotic postmenopausal women. Journal of Physical Activity and Health 2008;5(6):844–53.

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Uusi-Rasi 2005 {published data only} Uusi-Rasi K, Sievänen H, Heinonen A, Beck TJ, Vuori I. Determinants of changes in bone mass and femoral neck structure, and physical performance after menopause: a 9-year follow-up of initially peri-menopausal women. Osteoporosis International 2005;16(6):616–22. Villareal 2003 {published data only} Villareal DT, Binder EF, Yarasheski KE, Williams DB, Brown M, Sinacore DR, et al.Effects of exercise training added to ongoing hormone replacement therapy on bone mineral density in frail elderly women. Journal of the American Geriatrics Society 2003;51(7):985–90. White 1984 {published data only} White MK, Martin RB, Yeater RA, Butcher RL, Radin EL. The effects of exercise on the bones of postmenopausal women. International Orthopaedics 1984;7(4):209–214. Xu 2004 {published data only} Xu H, Lawson D, Kras A. A study on Tai Ji exercise and traditional Chinese medical modalities in relation to bone structure, bone function and menopausal symptoms. Journal of Chinese Medicine 2004;74:10–14. Yamazaki 2004 {published data only} Yamazaki S, Ichimura S, Iwamoto J, Takeda T, Toyama Y. Effect of walking exercise on bone metabolism in postmenopausal women with osteopenia/osteoporosis. Journal of Bone and Mineral Metabolism 2004;22(5):500–8.

References to studies awaiting assessment Ilona 2010 {published data only} Ilinca I, Avramescu T, Shaao M, Rosulescu E, Zavaleanu M. The role of high - impact exercises in improve bone mineral density in postmenopausal women with osteopenia or osteoporosis. Journal of Physical Education and Sport 2010;27(2):110. Karaarslan 2010 {published data only} Karaarslan S, Buyukyazi G, Taneli F, Ulmans C, Tikiz C, Gumuser G, et al.Effects of different intensity resistance exercise programs on bone turnover markers, osteoprotegerin and receptor activator of nuclear factor kappa ligand in post-menopausal women. Turkiye Klinikleri Journal of Medical Sciences 2010;30(1):123–34. Kemmler 2004a {published data only} Kemmler W, Von Stengel S, Beeskow C, Pintag R, Lauber D, Weineck J, et al.Optimization of bone anabolic exercise in early postmenopausal women according to results from animal and athletic studies. Osteologie 2004;13(2):65–77.

References to ongoing studies Wayne 2010 {published data only} Wayne PM, Buring JE, Davis RB, Connors EM, Bonato P, Patritti B, et al.Tai Chi for osteopenic women: design and rationale of a pragmatic randomized controlled trial. BMC Musculoskeletal Disorders 2010;11:40.

Additional references Ammann 2003 Ammann P, Rizzoli R. Bone strength and its determinants. Osteoporosis International 2003;14 Suppl 3:13–8. Berard 1997 Berard A, Bravo G, Gauthier P. Meta-analysis of the effectiveness of physical activity for the prevention of bone loss in postmenopausal women. Osteoporosis International 1997;7(4):331–7. Bessette 2008 Bessette L, Ste-Marie LG, Jean S, Davison KS, Beaulieu M, Baranci M, et al.The care gap in diagnosis and treatment of women with a fragility fracture. Osteoporosis International 2008;19(1):79–86. Bonaiuti 2002 Bonaiuti D, Shea B, Lovine R, Negrini S, Welch V, Kemper HHCG. Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database of Systematic Reviews 2002, Issue 3. [DOI: 10.1002/ 14651858.CD000333] Burge 2007 Burge R, Dawson-Hughes B, Solomon DH, Wong J B, King A, Tosteson A. Incidence and Economic Burden of Osteoporosis-Related Fractures in the United States, 20052025. Journal of Bone and Mineral Research 2007;22(3): 465–475. [DOI: 10.1359/jbmr.061113] CDC 1991 Consensus Development Conference. Propylaxis and treatment of osteoporosis. Osteoporosis International 1991; 1:114–7. Cooper 1993 Cooper C. The epidemiology of fragility fractures: is there a role for bone quality?. Calcified Tissue International 1993; 53(Suppl 1):S23–6. Cranney 2006 O’Donnell S, Cranney A, Wells GA, Adachi J, Reginster JY. Strontium ranelate for preventing and treating postmenopausal osteoporosis. Cochrane Database of Systematic Reviews 2006, Issue 4. [DOI: 10.1002/ 14651858.CD005326.pub3] Cummings 1993 Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, et al.The Study of Osteoporotic Fractures Research Group. Bone density at various sites for prediction of hip fractures. Lancet 1993;341(8837):72–5. Deeks 1998 Deeks J. Odds ratios should be used only in case-control studies and logistic regression analysis (letter). BMJ 1998; 317:1115. Deeks 2011 Deeks JJ, Higgins JPT, Altman DG (editors). Chapter 9: Analysing data and undertaking meta-analyses. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March

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2011]. The Cochrane Collaboration, 2011.. Available from www.cochrane-handbook.org. Dickersin 1994 Dickersin K, Scherer R, Lefebvre C. Identifying relevant studies for systematic reviews. BMJ 1994;309(6964): 1286–91. Gillespie 2009 Gillespie LD, Robertson MC, Gillespie WJ, Lamb SE, Gates S, Cumming RG, et al.Interventions for preventing falls in older people living in the community. Cochrane Database of Systematic Reviews 2009, Issue 2. [DOI: 10.1002/14651858.CD007146.pub2] Haguenauer 2004 Haguenauer D, Shea B, Tugwell P, Wells GA, Welch V. Fluoride for treating postmenopausal osteoporosis. Cochrane Database of Systematic Reviews 2000, Issue 4. [DOI: 10.1002/14651858.CD002825] Haynes 1994 Haynes R, Wilczynski N, McKibbon KA, Walker CJ, Sinclair JC. Developing optimal search strategies for detecting clinically sound studies in MEDLINE. Journal of the American Medical Informatics Association 1994;1:447–8. Higgins 2011 Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org. Hind 2007 Hind K, Burrows M. Weight-bearing exercise and bone mineral accrual in children and adolescents: a review of controlled trials. Bone 2007;40(1):14–27. [PUBMED: 16956802] Marshall 1996 Marshall D, Hans Wedel O. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996;312(7041):1254–39. Mayoux-Benhamou 1997 Mayoux-Benhamou MA, Bagheri F, Roux C, Auleley GR, Rabourdin JP, Revel M. Effect of Ppsoas training on postmenopausal lumbar bone loss: a 3-year follow-up study. Calcified Tissue International 1997;60(4):348–53. Nikander 2010 Nikander R, Sievänen H, Heinonen A, Daly RM, UusiRasi K, Kannus P. Targeted exercise against osteoporosis: A systematic review and meta-analysis for optimising bone strength throughout life. BMC Medicine 2010;8:47. [DOI: 10.1186/1741-7015-8-47] Papaioannou 2010 Papaioannou A, Morin S, Cheung A, Atkinson S, Brown JP, Feldman S, et al.2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. Canadian Medical Association Journal 2010;182 (17):1829–30. [DOI: 10.1503/cmaj.100771]

RevMan 2011 The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan).. 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011. Robling 2002 Robling AG, Hinant FM, Burr DB, Turner CH. Shorter, more frequent mechanical loading sessions enhance bone mass. Medicine and Science in Sports and Exercise 2002;34 (2):196–201. Schmitt 2009 Schmitt NM, Schmitt J, Dören M. The role of physical activity in the prevention of osteoporosis in postmenopausal women-An update. Maturitas 2009;63(1):34–8. Schünemann 2011 Schünemann HJ, Oxman AD, Higgins JPT, Vist GE, Glasziou P, Guyatt GH. Chapter 11: Presenting results and ’Summary of findings’ tables In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org. Taaffe 1997 Taaffe DR, Robinson TL, Snow CM, Marcus R. Highimpact exercise promotes bone gain in well-trained female athletes. Journal of Bone and Mineral Research 1997;12(2): 255–60. [DOI: 10.1359/jbmr.1997.12.2.255] Wayne 2007 Wayne PM, Kiel DP, Krebs DE, Davis RB, SavetskyGerman J, Connelly M, et al.The effects of Tai Chi on bone mineral density in postmenopausal women: A systematic review. Archives of Physical Medicine and Rehabilitation 2007;88(5):673–80. Wells 2008a Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Welch V, et al.Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database of Systematic Reviews 2008, Issue 1. [DOI: 10.1002/14651858.CD001155.pub2] Wells 2008b Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Welch V, et al.Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database of Systematic Reviews 2008, Issue 1. [DOI: 10.1002/14651858.CD003376.pub3] Wells 2008c Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Welch V, et al.Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database of Systematic Reviews 2008, Issue 1. [DOI: 10.1002/14651858.CD004523.pub3] WHO 1994 Report of a WHO Study Group. Assessment of fracture risk and its application to screening for postmenopausal

Exercise for preventing and treating osteoporosis in postmenopausal women (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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osteoporosis. World Health Organization Technical Report Series 1994;843:1–129. WHO 2003 World Health Organisation. Adherence to long term therapies: evidence for action. World Health Organisation, Geneva, Switzerland 2003:3–4. Winett 2001 Winett RA, Carpinelli RN. Potential health related benefits of resistance training. Preventative Medicine 2001;33: 503–13. [DOI: 10.1006/pmed.2001.0909] Wolff 1999 Wolff I, Van Croonenborg JJ, Kemper HC, Kostense PJ, Twisk JW. The effect of exercise training programs on bone mass: a meta-analysis of published controlled trials in preand postmenopausal women. Osteoporosis International 1999;9(1):1–12.

Zebaze 2010 Zebaze R, Ghasem-Zadeh A, Bohte A, Iuliano-Burns S, Mirams M, Price RI, Mackie EJ, Seeman E. Intracortical remodelling and porosity in the distal radius and postmortem femurs of women: a cross-sectional study. The Lancet 2010;375(9727):1729–36. [DOI: 10.1016/ S0140-6736(10)60320-0.]

Zerwekh 1998 Zerwekh JE, Ruml LA, Gottschalk F, Pak CYC. The effects of twelve eeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects. Journal of Bone and Mineral Research 1998;13(10):1594-1601. [DOI: 10.1359/ jbmr.1998.13.10.1594] ∗ Indicates the major publication for the study

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CHARACTERISTICS OF STUDIES

Characteristics of included studies [ordered by study ID] Bemben 2000 Methods

Type of study: RCT

Participants

Number of participants randomised = 35 Losses: 10 (4 high repetitions, 3 high load, 3 control) Age: 41-60 years Setting: USA Inclusion:1-7 yr postmenopausal and had not performed any resistance training in the previous 6 months Exclusion: 1) diagnosed osteoporosis or a BMD site ≥ 2.5 SD below the mean for the young-adult reference population; 2) a history of cardiovascular disease; 3) physical or orthopaedic disabilities; 4) a history or current diagnosis of renal disease, chronic digestive or eating disorders, rheumatoid arthritis, or thyroid disease; 5) a history of prolonged bed rest; and 6) current or recent use of medications that affect bone density (i.e. oestrogen, steroid hormones, calcitonin or corticosteroids)

Interventions

Exercise group high load (HL) (NWBHF) (n = 10): 10-min warm-up, approximately 45 min of weight lifting, and ended with a 5-min cool-down. Quadriceps extension, hamstring flexion, leg press, shoulder press, biceps curl, triceps extension, seated row and latissimus pull. High load low reps (8 reps 80% 1RM) Exercise group high repetition (HR) (NWBLF) (n = 7): 10-min warm-up, approximately 45 min of weight lifting, and ended with a 5-min cool-down. Quadriceps extension, hamstring flexion, leg press, shoulder press, biceps curl, triceps extension, seated row and latissimus pull. Low load high reps (16 reps 40% 1RM) Control Group (n = 8): usual activity Duration and intensity: 3 sessions per week for 6 months Supervisor: Research assistants Supervision: Group Setting: Gym

Outcomes

% Change BMD spine, hip (total hip, neck of femur, trochanter, Wards triangle), total body

Notes

Compliance/adherence: average attendance for the 6-month intervention was 93% for HR and 87% for HL Adverse events: none reported Converted absolute data to % change

Risk of bias Bias

Authors’ judgement

Random sequence generation (selection Unclear risk bias)

Support for judgement Subjects were matched according to the BMD of the spine after baseline testing, then they were randomly assigned, method not described

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Bemben 2000

(Continued)

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

High risk

’As-treated’ analysis done, drop-outs mentioned but not accounted for in analysis

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Unclear risk

Not reported

Comparability of exercise and control Low risk group at entry

No significant group differences existed in number of years postmenopausal or in body composition variables

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 6 months, no followup data reported

Bergstrom 2008 Methods

Type of study: RCT

Participants

Number of participants randomised = 112 Losses: 20 (Exercise: 1 failed to attend DXA, 11 did not start training or trained less than 6 months, Control: 8 undertook other exercise) Age: 59.6 Exercise, 58.9 control Setting: Sweden Inclusion: postmenopausal women 45 to 65 years with forearm fractures and T-scores from −1.0 to −3.0 (total hip or spine) Exclusion: T-score lower than −3 at any site, had any disease known to interfere with bone metabolism, were on cortisone therapy or anti-resorptive medication, including hormone replacement therapy, had a BMI lower than 19.9 or higher than 30.9, or were already training at the level of or above that of the intervention

Interventions

Exercise group (COMB) (n = 48): 3 fast 30-minute, walks and two sessions of onehour training per week. 5-minute warm-up, 25 minutes of strengthening exercises for the arms, legs, back and stomach, 25 minutes of aerobic exercise, and 5 minutes of stretching. Individuals chose own level and intensity and encouraged to increase level if possible Control Group (n = 44): usual activity Duration and intensity: 5 sessions per week for 12 months Supervisor: nurses Supervision: group Setting: clinic

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Bergstrom 2008

(Continued)

Outcomes

% change BMD DEXA spine, total hip

Notes

Compliance/adherence: controlled by study nurse (compliance was 95%) Adverse events: none reported 80% power difference, 3% with 64 in each group Converted absolute data to % change

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

Predefined random number table

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Low risk

Per protocol and intention-to-treat analysis

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Unclear risk

Not reported

Comparability of exercise and control Unclear risk group at entry

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 1 year, no follow-up data reported

Bocalini 2009 Methods

Type of study: RCT

Participants

Number of participants randomised = 35 Losses: 10 (3 exercise, 2 control, plus 5 in exercise did not achieve 90% participation) Age: range 57-75 years Setting: Brazil Inclusion: women older than 55 years (and able to train 3 x per week for 24 weeks) Exclusion: participation in a regular and structured physical activity for the last 3 months; recent hospitalisation; motor deficiency; symptomatic cardiorespiratory disease; non controlled hypertension or metabolic syndrome; severe renal or hepatic disease; cognitive

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Bocalini 2009

(Continued)

impairment or debilitating conditions; marked obesity with inability to exercise; recent bone fracture (during the past 2 years); use of any medication that may alter calcium or bone metabolism; other medical contraindications to exercise Interventions

Exercise group strength training (NWBHF) (n = 15): Eccentric muscle action was emphasised for leg press, chest press, leg curl, latissimus pull down, elbow flexion, elbow extension, leg extension, upper back row, military press, hip abductor, hip adductor and abdominal curls. 10-minute warm-up, (running with low impact at 50% MHR), one set 50% 1 RM, progressing to 3 sets 85% 1 RM Control Group (n = 10): usual activity Duration and intensity: 1 hr sessions 3 x per week in non-consecutive days for 24 weeks Supervisor: fitness instructor and researchers Supervision: probably group Setting: gym

Outcomes

% change BMD DEXA lumbar spine, femoral neck

Notes

Compliance/adherence: all completers required to participate in 90% of programme Adverse events: none reported Converted SE to SD

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation mentioned but insufficient information to permit judgement of ’high risk’ or ’low risk’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

’As-treated’ analysis done, drop outs mentioned and 5 in exercise group did not achieve 90% participation, thus were excluded

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Participants not blinded

Blinding (assessor)

Low risk

Investigator blind to subject condition

Comparability of exercise and control Low risk group at entry

No differences were identified between groups, concerning biometric characteristics, muscle strength or bone densitometry parameters

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Bocalini 2009

(Continued)

Appropriateness of duration of surveillance High risk

Outcomes only on immediately postintervention (24 weeks), no follow-up data reported

Bravo 1996 Methods

RCT

Participants

Number of participants randomised = 142 Losses: 18 (equally divided across groups) Age: mean 60±6 years Setting: Canada Inclusion: menopausal (> 12 months) community-dwelling women between the ages of 50 and 70, with low bone mass (spine > 1g/cm2 , proximal femur >0.9g/cm2 ), no contradictions to undertaking physical exercise without supervision Exclusion: not stated

Interventions

Exercise group (DWBLF) (n = 61): warm up, 25 min of rapid walking: 15 min of stepping down and up or aerobic dancing, each had to progressively reach 60-70% of her heart rate reserve, localised exercise: 10-15 min of exercises in sitting, standing, prone position, involving the muscles of upper limbs, abdominals and the back, cool down period with relaxation movements, stretching, balancing and coordination exercises Control group (n = 63): to continue their daily routine activities plus education Duration and intensity: 1 hour long exercise classes, 3/week per 12 months Supervisor: exercise leaders Supervision: group Setting: gym

Outcomes

BMD spine, BMD neck of femur

Notes

Compliance/adherence: not reported Adverse events: none reported Converted absolute data to % change.

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

Random number tables, block randomisation and stratified by age and HRT use

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Low risk

Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups Intention-to-treat analysis performed

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Bravo 1996

(Continued)

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’ but exercise is difficult to blind

Blinding (assessor)

Low risk

Three assessors blind to group allocation

Comparability of exercise and control Low risk group at entry

No significant differences between groups apart from years postmenopause (longer in control group) and use of oestrogen (more in exercise group)

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 12 months, no follow-up data reported

Brentano 2008 Methods

Type of study: RCT

Participants

Number of participants randomised = 28 Losses: not stated Age: not stated Setting: Brazil Inclusion: not stated Exclusion: not stated

Interventions

Exercise group Circuit training (NWBLF) (n = 9): No rest between exercises; progression of loads. Warm-up: 5 minutes cycloergometer or treadmill, 20-10 repetitions and 4560% 1RM, performing 2-3 sets for each exercise, leg press, hip abduction, hip adduction, knee extension, chest fly, reverse fly, arm curl, triceps push-down, sit-ups and back extension Exrcise group High intensity (NWBHF) (n = 10): 2 min rest between exercises; progression of loads. Warm-up: 5 minutes cycloergometer or treadmill. 20-6 repetitions and 45-80% 1RM, performing 2-4 sets for each exercise, leg press, hip abduction, hip adduction, knee extension, chest fly, reverse fly, arm curl, triceps push-down, sit-ups and back extension Control Group (n = 9): usual activity Duration and intensity: 1 hr 3 x week for 24 weeks Supervisor: not stated Supervision: group Setting: gym

Outcomes

BMD femoral neck, femoral trochanter, Ward’s triangle, intertrochanter

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Brentano 2008

(Continued)

Notes

Compliance/adherence: not stated Adverse events: none reported Data presented graphically only

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Subjects were divided into 2 subgroups: taking HRT (n = 14) and not taking HRT (n = 14). Then, the subgroups were randomly divided but insufficient information to permit judgement of ’high risk’ or ’low risk’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

Unclear risk

Not possible

Blinding (assessor)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Comparability of exercise and control Unclear risk group at entry

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Appropriateness of duration of surveillance High risk

Only immediately postintervention data, no follow-up data reported

Chan 2004 Methods

Type of study: RCT

Participants

Number of participants randomised = 132 Losses: 24 (13 Exercise, 11 control) Age: 54 (±3.5) years Setting: Hong Kong Inclusion: ceased menstruation between 1 and 10 years (1) no regular participation in physical exercise (not > 0.5h/wk); (2) no hormone replacement therapy or drug treatment known to affect bone metabolism or cause spontaneous bone loss; (3) no conditions such as hypo- or hyperparathyroidism and hypo- or hyperthyroidism, or renal or liver disease; (4) no history of fractures; and (5) a body mass index (BMI) above 30kg/m2

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Chan 2004

(Continued)

Exclusion: Interventions

Exercise group (DWBLF) (n = 67): Yang Tau Chi Chuan style emphasises slow and smooth movement involving major muscle groups, at a constant speed while practicing Control Group (n = 65): usual activity Duration and intensity: 50 mins 5x week for 12 months Supervisor: not reported Supervision: group Setting: community

Outcomes

% change BMD DXA lumbar spine, neck of femur, total hip, trochanter, distal tibia Fracture rate

Notes

Compliance/adherence: Average attendance rate of the TCC exercise was 4.2±0.9 days per week Adverse events: Fractures occurred during the follow-up. During the 12-month study period, a total of 4 fracture cases were documented, including 3 fracture in the control group (1 vertebral fracture, 1 Colles’ fractures, 1 fracture at the fifth metacarpal) and 1 in the TCC group (proximal fibular fracture). All injury cases resulted from overloading during work (the case with vertebral fracture) or falls (the other 3 cases) Sample size of 45 for each group was estimated to achieve a statistical power of 0.8 after excluding a dropout rate of approximately 25% during 12-month follow-up Converted absolute data to % change

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation mentioned but insufficient information to permit judgement of ’high risk’ or ’low risk’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

’As-treated’ analysis done drop-outs mentioned

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Unclear risk

Not reported

Comparability of exercise and control Low risk group at entry

No significant differences in characteristics at baseline

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Chan 2004

(Continued)

Appropriateness of duration of surveillance High risk

Only immediately postintervention data 12 months, no followup data reported

Cheng 2002 Methods

Type of study: RCT

Participants

Number of participants randomised = 80 Losses: 28 (non HRT 8 exercise, 5 control; HRT 10 exercise, 5 control) Age: 50-57 years Setting: Finland Inclusion: 50 -55-year-old women, no serious cardiovascular or locomotor system problems, a body mass index of 33 kg/m2 , and not currently or previously (no longer than 6 months and at least 2 years prior to screening) using medications including oestrogen, fluoride, calcitonin, bisphosphonate’s, and steroids, last menstruation at least 0.5 years but not more than 5 years ago Exclusion: not reported

Interventions

No HRT Exercise group (DWBHF) (n = 20): 5 circuit-training periods, each lasting 8 -10 weeks. These periods were interrupted by three high-impact aerobic dance periods, each of 2 week duration, and a summer pause for 5 weeks. Each session commenced with a 10 min warm-up period and concluded with stretching activities. During the first two circuit training periods, three rotations were performed of skipping (30 sec) , bounding over soft hurdles (13-16 cm), drop jumping (10-15 cm), and hopping (on one leg 10 times, added during the second training period). The following three periods comprised four rotations of bounding (19-25 cm), drop jumping (20-25 cm), hopping (10 times per leg) and leaping (10 times). In addition, all circuit training sessions included 3 or 4 of the following resistance exercises for the upper body: chest fly, latissimus pull down, military press, seated row and biceps curl. The home exercise programme was also designed as a circuit training routine comprising three rotations of skipping (30 sec), hopping (10 times per leg) and drop jumping (15 cm). In addition, exercises to strengthen the abdominal and lower back region were included. Average GRF was 4.3 times body weight (BW) for drop-landing from a 10 cm height, and 5.2 times BW from 20 and 25 cm heights; bounding over the hurdles 4.9-5.1 BW, skipping, hopping, and leaping 3.8, 3.4, and 4.8 BW, respectively No HRT Control Group (n = 20): usual activity HRT Exercise group (DWBHF) (n = 20): as exercise group above HRT Control Group (n = 20): usual activity Duration and intensity: 2 x supervised and 4 non supervised sessions per week 12 months Supervisor: not stated Supervision: group/individual Setting: gym/home

Outcomes

BMD DXA proximal femur, tibial shaft Cortical tibia

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Cheng 2002

(Continued)

Notes

Compliance/adherence: average attendance 1 x per week Adverse events: none reported Converted absolute data to % change

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

Randomisation by drawing lots

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

’As-treated’ analysis done drop-outs mentioned but not controlled for

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

Unclear risk

Stated double-blind (may be related to the HRT component) but insufficient information to permit judgement of ’high risk’ or ’low risk’

Blinding (assessor)

Unclear risk

Stated double-blind (may be related to the HRT component) but insufficient information to permit judgement of ’high risk’ or ’low risk’

Comparability of exercise and control Low risk group at entry

No significant differences in physical characteristics at baseline

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 12 months, no follow-up data reported

Chilibeck 2002 Methods

Type of study: RCT

Participants

Number of participants randomised = 57 Losses: 9 (4 non bisphosphonate exercise, 3 bisphosphonate exercise, 2 non bisphosphonate control) Age: mean age of groups ranged from 55.9 to 58.8 years Setting: Canada Inclusion: postmenopausal status (cessation of bleeding status for one year) Exclusion: skeletal; disorders, kidney disease or bone related disorders, chronic disease or chronic medication likely to affect metabolism or calcium imbalance. BMD z-score < -2.

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Chilibeck 2002

(Continued)

0, HRT, bisphosphonate therapy in last year, recent participation in exercise programmes, history of cardiac disease or high blood pressure Interventions

All received 10 µg vitamin D/d and those in non bisphosphonate received 500 mg calcium carbonate/d Non bisphosphonate exercise group (NWBHF) (n = 10): warm up cycling and stretching, 2 sets 8-10 reps of; bench press, latissimus dorsi pull down, shoulder press, biceps curl, back extension, hip extension, flexion, adduction and abduction, knee flexion, knee extension and leg press. initially 70% 1RM then progressed Non bisphosphonate control Group (n = 12): usual activity Bisphosphonate exercise group (NWBHF) (n = 12): as above Bisphosphonate control group (n = 14): usual activity Duration and intensity: 3 days per week for 12 months Supervisor: not stated Supervision: individual Setting: gym

Outcomes

% change BMD spine, total hip, femoral neck, trochanter, Ward’s triangle, whole body % change whole body BMC

Notes

Compliance/adherence: Non bisphosphonate exercise group 77.6%, bisphosphonate exercise group 74.8% of training sessions Adverse events: none reported 9 subjects per group would demonstrate change α of 0.05 with 80% power Converted SE to SD

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation mentioned but insufficient information to permit judgement of ’high risk’ or ’low risk’

Allocation concealment (selection bias)

Low risk

Insufficient information although mentions double-blind

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

’As-treated’ analysis done drop-outs mentioned but not controlled for

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

Unclear risk

Mentions double-blind but probably relates to medication status

Blinding (assessor)

Low risk

States double-blind

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Chilibeck 2002

(Continued)

Comparability of exercise and control Low risk group at entry

No significant differences in characteristics at baseline

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 12 months, no follow-up data reported

Chow 1987 Methods

RCT

Participants

Number of participants randomised = 58 Losses: 4 controls, 2 (DWBLF), 4 (COMB) Age: mean age 56 years Setting: Canada Inclusion: no history of: fractures, metabolic bone disease, renal, liver or thyroid disorders, gastrectomy, alcoholism, oestrogen or other drugs affecting bone metabolism Exclusion: not reported

Interventions

Exercise group (DWBHF) (n = 19): 5-10 min of stretching and calisthenic warm up, exercise followed by 30 min of aerobic activities at 80% MaxHR (walking, jogging, dance) Exercise group (COMB) (n = 20) 5-10 min of stretching and calisthenic warm up, exercise followed by 30 min of aerobic activities at 80% MaxHR (walking, jogging, dance) plus 10-15 min session of low intensity strength training (isometric and isotonic contractions of limbs and trunk muscles. 10 repetitions for each muscle group Control Group (n = 19): continue daily routine activities, refrain from any regular fitness exercises (telephoned 4 x per year) Duration and intensity: 3 sessions per week for 1 year Supervisor: certified fitness instructor Supervision: group Setting: hospital gym

Outcomes

CaBI.

Notes

Compliance/adherence: overall attendance at exercise class was 70% Adverse events: 1 (DWBLF) knee pain; 2 (COMB) knee pain; 1 (COMB) back pain Power calculation done 15 per group, and all groups of appropriate size Converted absolute data to % change

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

Random number generator

Allocation concealment (selection bias)

Sequential sealed envelopes

Low risk

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Chow 1987

(Continued)

Incomplete outcome data (attrition bias) All outcomes

Low risk

Details supplied. Discussion of reasons for dropout. Comparison with dropout and excluded groups

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Not practical for exercise programme

Blinding (assessor)

Low risk

Assessors blind

Comparability of exercise and control Low risk group at entry

Initial mean values of bone mass and aerobic capacity were within normal ranges for all groups

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 12 months, no follow-up data reported

Chubak 2006 Methods

Type of study: RCT

Participants

Number of participants randomised = 173 Losses: 3 exercise group Age:50-75 years, mean 61 years Setting: USA Inclusion: overweight/obese, postmenopausal women sedentary (< 60 min/wk of moderate-to vigorous-intensity exercise), overweight (BMI 25.0 to 30.0 kg/m2, or BMI between 24.0 and < 25.0 kg/m2 and percent body fat > 33%) or obese (BMI > 30.0 kg/ m2), no menstrual periods for the previous 12 months Exclusion: using hormone therapy in the past 6 months, being too physically active, having medical conditions contraindicating moderate to vigorous-intensity exercise, having a clinical diagnosis of diabetes, and currently using tobacco

Interventions

Exercise group (COMB) (n = 87): moderate-intensity aerobic exercise (60-75% of maximal heart rate), 40% of observed maximal heart rate for 16 min per session and gradually increased to 60-75% of maximal heart rate for 45 min per session by week 8. Treadmill walking and stationary bicycling. Strength training, consisting of two sets of 10 repetitions of leg extension, leg curls, leg press, chest press, and seated dumbbell row Control Group (n = 86): 45-min stretching sessions once a week Duration and intensity: 45 mins, 5 days per week for 12 months (3 supervised sessions per week months 1-3 and to exercise 2 d/wk at home; months 4-12 at least one of the three supervised sessions weekly and to exercise 4 d/wk either at home or elsewhere Supervisor: not stated Supervision: group and individual Setting: gym and home

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Chubak 2006

(Continued)

Outcomes

BMD Total body

Notes

Compliance/adherence: exercisers averaged 172 min/wk (SD = 89) of exercise Adverse events: none reported Converted absolute data to % change

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

Stratifying on body mass index (BMI) (above and below 27.5 kg/m) randomly assigned women to either the exercise or the stretching arm of the trial. Randomisation was performed by random number generation

Allocation concealment (selection bias)

Low risk

Group assignment was placed in a sealed envelope, which was opened by the study coordinator at the time of randomisation

Incomplete outcome data (attrition bias) All outcomes

Low risk

Intention-to-treat analysis performed

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

Unclear risk

Not possible

Blinding (assessor)

Low risk

Technicians blinded to group allocation

Comparability of exercise and control Low risk group at entry

Groups similar with respect to demographic characteristics and known predictors of bone mineral density and other subject characteristics

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 12 months, no follow-up data reported

Chuin 2009 Methods

Type of study: RCT

Participants

Number of participants randomised = 34 Losses: not reported Age: 61-73 years, 66.1 years Setting: Canada Inclusion: healthy, Caucasian, without major incapacity, no medication influencing metabolism, non-smoker, moderate drinker, NBMI 18-30 kg/m2 , no consumption of

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Chuin 2009

(Continued)

antioxidant supplements during last month, postmenopausal, no HRT Exclusion: not reported Interventions

Antioxidants (600 mg/day vitamin E and 1,000 mg/day vitamin C) Placebo and Exercise group (NWBHF) (n = 8): 15 min warm up, treadmill, cycle and stretching; 45 mins resistance training leg press, bench press, leg extension, shoulder press, sit up, seated row, triceps extensions, biceps curl. 3 sets 8 reps per set at 80% 1RM Placebo Control Group (n = 7): usual activity Antioxidant exercise group (NWBHF) (n = 8): as exercise above Antioxidant control group (n = 8): usual activity Duration and intensity: 60 mins sessions 3 x week for 6 months Supervisor: not stated Supervision: groups Setting: gym

Outcomes

BMD spine, femoral neck

Notes

Compliance/adherence: not stated but one missed session per month accepted for compliance purposes Adverse events: none reported Converted absolute data to % change

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation mentioned but insufficient information to permit judgement of ’high risk’ or ’low risk’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

Completer analysis. Loss not accounted for

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Comparability of exercise and control Low risk group at entry

Groups were similar for baseline characteristics, body composition, strength

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Chuin 2009

(Continued)

Appropriateness of duration of surveillance High risk

Only immediately postintervention data 6 months, no followup data reported

Ebrahim 1997 Methods

RCT

Participants

Number of participants randomised = 165 Losses: 32 exercise group, 36 control Age: mean ages (66-70) years Setting: UK Inclusion: women who had sustained an upper arm fracture in the past 2 years Exclusion: not recorded

Interventions

Exercise group (DWBLF) (n = 49): self paced brisk walking Control Group (n = 48): upper limb exercises for fracture Duration and intensity: 40 mins 3 x week for 2 years Supervisor: nurse Supervision: seen every 3 months and phone calls monthly Setting: home

Outcomes

BMD lumbar spine, femoral neck

Notes

Compliance/adherence: All women completing trial reported carrying out regular brisk walking at least 40 mins three times per week Adverse events: 1 exercise related trauma reported. By the end of the trial the brisk walking group had sustained a significant excess of 15.2 falls per 100 person years No power calculation. Very small study (15 total, 5 per exercise group)

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

Computer generated randomised allocation

Allocation concealment (selection bias)

Low risk

Sequentially numbered envelopes

Incomplete outcome data (attrition bias) All outcomes

Low risk

Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups. Data for all participants, including one dropout at 11 months

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

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Ebrahim 1997

(Continued)

Blinding (participant)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’ but exercise is difficult to blind

Blinding (assessor)

High risk

Same nurse saw both groups

Comparability of exercise and control Low risk group at entry

No significant differences between groups apart from slightly younger women in the exercise group

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 2 years, no followup data reported

Englund 2005 Methods

Type of study: RCT

Participants

Number of participants randomised = 48 Losses: 3 exercise, 5 control Age: 66-87 years Setting: Sweden Inclusion: not reported Exclusion:dementia, current smoking, current hormone replacement therapy (HRT), and use of a walking aid, cardiovascular disease, or functional disability, of a degree that would contraindicate physical exercise

Interventions

Exercise group (COMB) (n = 24): 10 min of warming-up, followed by a mix of aerobic (walking and jogging), strengthening (legs, abdominal, and back muscles were trained by means of body resistance only) , balance and coordination exercises for 27 min. The programme then ended with 11 min of cooling down, stretching and relaxation. If participants missed out on a training session they were advised to perform a home exercise programme instead. This programme included brisk walking for 30 min, squats with 3·10 repetitions, and training of hand grip with a piece of T-foam for 3·15 repetitions Control Group (n = 24): Duration and intensity: 50 mins twice a week for 12 months, with a 5-week break during the summer vacation Supervisor: physiotherapist Supervision:not reported Setting:not reported

Outcomes

BMD spine, femoral neck, trochanter, Ward’s triangle, arms, total body (g/cm2 ) BMC total body (g)

Notes

Compliance/adherence: mean percentage of scheduled sessions attended for the exercise group was 67% Adverse events: not recorded A sample size of 24 in each group, a-level of 0.05 and standard deviation of 10% gave 30% power to detect a 5% difference in change between the two groups Converted absolute data to % change

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Englund 2005

(Continued)

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Pair-wise age matched, randomised mentioned but insufficient information to permit judgement of ’high risk’ or ’low risk’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

’As-treated’ analysis done drop-outs mentioned but not accounted for in analysis

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Unclear risk

Unclear but the same investigator carried out all analyses

Comparability of exercise and control Low risk group at entry

There was no significant difference in total BMD between the groups at the beginning of the study but mean age for menopause was significantly higher in the control group

Appropriateness of duration of surveillance Low risk

Immediately postintervention data 12 months and 5 year followup data reported

Going 2003 Methods

Type of study: RCT

Participants

Number of participants randomised = 320 (HRT, n = 159; NHRT, n = 161) Losses: Retention rates were 82%, 89%, 78% and 84% for EX/NHRT, NEX/ HRT, EX/NHRT and NEX/NHRT, respectively. The dropout rate for EX (20%) and NEX (13%), NonHRT (19%), HRT (14%) Age: 40-65 years Setting: USA Inclusion: women who were undergoing hormone replacement therapy for at least 1 year and not more than 5.9 years AND women who had not used HRT during the preceding year. Surgical or natural menopause (3-10.9 years). BMI < 33, non smoker, no history of osteoporotic fractures, initial lumbar spine and hip BMD > Z -3.0. Cancer and cancer treatment free for the last 5 years, excluding skin cancer, no medication affecting BMD, no beta blockers or steroids. Ca intake > 200 mg per day. Less than 120 min physical activity per week. No weightlifting or similar activity.

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Going 2003

(Continued)

Exclusion: not reported Interventions

Divided into HRT and non HRT groups. All groups taking Ca supplements as prescribed HRT Exercise group (DWBHF) (n = 86): supervised aerobic, weight-bearing and weightlifting exercise. Leg press, hack squats or Smith squats, lat pull downs, lateral rows, back extensions, right and left arm dumbbell presses, and rotary torso. Two sets of 6 to 8 repetitions 70% - 80% 1-RM. Weight bearing circuit comprising walk/jog, skipping, hopping, stair climbing/boxstep. Progressive impact regime HRT Control Group (n = 73): usual activity NonHRT Exercise group (DWBHF) (n = 91): supervised aerobic, weight-bearing and weight-lifting exercise as above Non HRT control Group (n = 70): usual activity Duration and intensity: 3x per week for 12 months Supervisor: trainer Supervision: group Setting: community

Outcomes

BMD DEXA total body, AP lumbar spine, neck of femur, trochanter

Notes

Compliance/adherence: Attendance at exercise sessions averaged 71.8±19.9% Adverse events: none reported Converted data from average change over one year to change at end of study

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation mentioned but insufficient information to permit judgement of ’high risk’ or ’low risk’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Low risk

Intention-to-treat analysis undertaken

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

Unclear risk

Not possible

Blinding (assessor)

Unclear risk

Not reported

Comparability of exercise and control Low risk group at entry

Groups similar at baseline for age, oestrogen levels, BMD and physical characteristics. Women not using HRT 1.6 years older

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Going 2003

(Continued)

Appropriateness of duration of surveillance High risk

Only immediately postintervention data 12 months, no followup data reported

Grove 1992 Methods

Type of study:RCT

Participants

Number of participants randomised = 15 Losses:1 subject in DWBHF group injured at 11 months, all post-test data from subject collected at this time point Age:46-64 yrs Setting: USA Inclusion: postmenopausal sedentary Caucasian women Exclusion: women who were active during last year; < 1 year or > 8 years postmenopausal; any renal, thyroid or liver disease; unwillingness to complete study; on medications that would affect calcium metabolism and absorption (except oestrogen)

Interventions

Exercise group (DWBLF) (n = 5): 15 mins warm up (stretching), 20 min exercise(low impact), 20 mins cool down (abdominal exercises). GRF for exercises, slow walk = 1.19 BW, fast walk = 1.49 BW, heel jack no jump = 1.34 BW, Charleston = 1.32 BW Exercise group (DWBHF) (n = 5): 15 mins warm up (stretching), 20 min exercise (high impact), 20 mins cool down (abdominal exercises). GRF for exercises, jumping jack = 3.29 BW, running-in-place = 2.47 BW, knee-elbow with jump = 2.79 BW Control Group (n = 5): usual activity Duration and intensity: 1 hr 3x week for 12 months Supervisor: not stated Supervision: group Setting: gym

Outcomes

Lumbar BMD at baseline, 6 and 12 months

Notes

Compliance/adherence: DWBLF = 80.0±6.6%, DWBHF = 82.6±4.1% Adverse events: 1 subject in DWBHF group injured at 11 months

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Matched by BMD and weight and randomly assigned to groups, method not stated

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

Small numbers in each group and only one loss

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Grove 1992

(Continued)

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Comparability of exercise and control Unclear risk group at entry

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 12 months, no follow-up data reported

Hatori 1993 Methods

Type of study:RCT

Participants

Number of participants randomised = 35 Losses: 2 from exercise group (lack of time) Age: 46-67 years Setting: Japan Inclusion: health postmenopausal women no history of oophrectomy Exclusion: not reported

Interventions

Exercise group: DWBLF (n = 9): stretching of the legs, torso and arms, followed by 30 min of walking on flat grass-covered ground moderate intensity: 90% of the heart rate DWBLF (n = 12): stretching of the legs, torso and arms, followed by 30 min of walking on flat grass-covered ground high intensity: 110% of the heart rate Control Group (n = 12): not reported Duration and intensity: 3 times/week during 7 months Supervisor: not stated Supervision: not clear Setting: not stated

Outcomes

% change in BMD Lumbar Spine (DEXA)

Notes

Compliance/adherence: not reported Adverse events: none reported Data for the group working at 110% HR was used in analysis

Risk of bias

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Hatori 1993

(Continued)

Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation reported but insufficient information about the sequence generation process to permit judgement of ’high risk’ or ’low risk’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

High risk

’As-treated’ analysis done, drop-outs mentioned but unclear as to which groups

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’ but exercise is difficult to blind

Blinding (assessor)

Low risk

Assessor had no knowledge of group allocation

Comparability of exercise and control Low risk group at entry

No significant difference between the groups at entry

Appropriateness of duration of surveillance High risk

Assessment at 7 months during the exercise programme of 7 month duration

Iwamoto 2001 Methods

Type of study: RCT

Participants

Number of participants randomised = 35 Losses: not reported Age: 53-77 years Setting: Japan Inclusion: postmenopausal women with diagnosis of osteoporosis Exclusion: not reported

Interventions

Concurrent calcium lactate 2.0 g and hydroxy vitamin D3 1 µg Exercise group (COMB) (n = 15): brisk walking and two sets a day of gymnastic training, consisting of 15 repetitions of straight leg raising, squatting, and abdominal and back muscle strengthening exercises Control Group (n = 20): usual activity Duration and intensity: daily for 12 months Supervisor: not reported Supervision: individual Setting: home

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Iwamoto 2001

(Continued)

Outcomes

% change BMD lumbar

Notes

Compliance/adherence: 100% at least five days per week Adverse events: none reported

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation mentioned but insufficient information to permit judgement of ’high risk’ or ’low risk’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

Unclear risk

Not possible

Blinding (assessor)

Unclear risk

Not reported. Insufficient information to permit judgement of ’high risk’ or ’low risk’

Comparability of exercise and control Low risk group at entry

No significant differences in initial lumbar BMD

Appropriateness of duration of surveillance High risk

Immediately postintervention data at 12 months, and followup after further year

Iwamoto 2005 Methods

Type of study: RCT

Participants

Number of participants randomised = 50 Losses: none reported Age: 70.6±8.7 control, 71.9±8.1 exercise Setting: Japan Inclusion:55-88 years, BMD score < 70 or 70-80%, history of osteoporotic fractures and chronic back pain Exclusion: musculoskeletal diseases considered to cause back pain

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Iwamoto 2005

(Continued)

Interventions

All participants received 5 mg alendronate Exercise group (DWBHF) (n = 25): whole body vibration plate at 20 Hz Control Group (n = 25): usual activity Duration and intensity: 4 mins, 1 x week for 12 months Supervisor: not reported Supervision: individual Setting: clinic

Outcomes

BMD vertebral fractures (radiographs)

Notes

Compliance/adherence: not stated Adverse events: 2 patients in control group and one in exercise group had falls

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation mentioned but insufficient information to permit judgement of ’high risk’ or ’low risk’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

’As-treated’ analysis done no drop outs mentioned

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Unclear risk

Not reported

Comparability of exercise and control Low risk group at entry Appropriateness of duration of surveillance Low risk

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Karinkanta 2007 Methods

Type of study: RCT

Participants

Number of participants randomised: 149 Losses: Total = 5 (4 from the training groups and 1 from control). (Drop out rate 3.4%) Age: 70-79 years: RES = 72.7 (2.5); BAL = 72.9 (2.3); COMB = 72.9 (2.2); CON = 72 (2.1) Sex: female Health status defined by authors: healthy older (> 70) females Setting: Finland Inclusion: willing to participate; age between 70-79 years; full understanding of study procedures; no history of illness contraindicating exercise or limiting participation in exercise programmes, no history of illness affecting balance or bones; no uncorrected vision problems; no medications known to affect balance or bone metabolism (12 months before enrolment) Exclusion: Involved in intense exercise more than 2x week or t-score for femoral neck bone mineral density (BMD) lower than -2.5

Interventions

Exercise group (DWBHF) = resistance training (n = 37). Progressing towards 75-80% 1RM 3 sets of 8-10. Large muscle group ex = sit-stand with weighted vest, squats, leg press, hip abduct, hip extension, calf raise, rowing with resistance machines. Different combinations of above were used in 10 week cycle to prevent monotony Exercise group (DWBHF) = balance jumping training (n = 37). Balance agility and impact exercise - 4 different aerobics and step aerobic programmes which were repeated. Progressive difficulty of steps, impact and jumps Exercise group (COMB) = resistance and balance jumping training (n = 38). Reistance and balance training on alternate weeks as above Control group = no training (n = 37) Duration and intensity: 3x weekly for 12 months, 50 mins. Warm up 7-10 mins; 25-30 mins exercise; 8-10 min cool down Supervisor: exercise leaders of UKK institute Supervision: groups but uncertain of number in each as not recorded Setting: not recorded

Outcomes

BMD DEXA • Bone mineral content BMC (g) • Cortical density (CoD) mg/cm

Notes

Compliance/adherence: mean training compliance = attendance 67% (RES = 74%; COMB = 67%; BAL = 59%) Adverse events: 14 due to musculoskeletal injuries or symptoms - 2 falls but they returned to classes. No difference in monthly reported health problems with exercisers and controls Fractures reported during 1 year follow-up period: Resistance group 1 hip 1 rib; Balance group 1 shoulder; Combined 1 hip; Control 1 patella Initial study data converted absolute data to % change. Follow-up study data was not presented in a useable form

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Karinkanta 2007

(Continued)

Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

Computer generated randomisation list drawn up by statistician, blinded to study participants and their characteristics, randomly allocated participants into 4 groups

Allocation concealment (selection bias)

Low risk

Statistician, blinded to study participants and their characteristics, randomly allocated participants into 4 groups

Incomplete outcome data (attrition bias) All outcomes

Low risk

Intention-to-treat and per protocol analysis

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’yes’ or ’no’ all main outcome measures reported on

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

Unclear risk

Not possible

Blinding (assessor)

Unclear risk

Insufficient information to permit judgement of ’yes’ or ’no’

Comparability of exercise and control Low risk group at entry

Statistics reported groups equivalent at baseline

Appropriateness of duration of surveillance Low risk

Immediately postintervention data at 12 months, and one year postcessation of intervention

Kerr 2001 Methods

Type of study: RCT

Participants

Number of participants randomised = 126 Losses: Retention at 2 years was 71% (59% in the S group, 69% in the F group, and 83% in the C group), Age: mean 60 (6.5) years Setting: Australia Inclusion: more than 4 years past menopause and physically capable of entering exercise groups but who were not already exercising at a moderate intensity more than 2 h/week Exclusion: hormone replacement or other medications or who had diseases known to affect bone density and those who had cardiovascular, physical, or orthopedic disabilities

Interventions

All subjects given 600 mg calcium per day Exercise group (NWBHF) (n = 24): warm-up consisting of brisk walking and stretching. This was followed by 30 minutes of resistance weight training exercises and progressively increased the loading, wrist curl, reverse curl, biceps curl, triceps pushdown, hip flexion, hip extension, latissimus dorsi pull down, and calf raise Exercise Group (NWBLF) (n = 30): as above but additional stationary bicycle riding

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Kerr 2001

(Continued)

with minimal increase in loading Control Group (n = 36): usual activity Duration and intensity: 1 hr sessions 3 x per week 2 years Supervisor: exercise physiologists Supervision: group Setting: gym Outcomes

BMD hip (total hip, femoral neck, trochanter, Wards triangle) , lumbar spine, and radial forearm

Notes

Compliance/adherence: Exercise compliance was very high in the first 6 months for both groups (S group, 90±12%; F group, 92± 8%) but declined from this point on. In the last 6 months of compliance was 61±23% for the S group and 67±20% for the F group. The average exercise compliance over 2 years was 74±13% in the S group and 77±14% in the F group Adverse events: none reported

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

Block randomisation to one of three groups

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

’As-treated’ analysis done drop-outs mentioned but unclear as to which groups

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Unclear risk

Not reported

Comparability of exercise and control Low risk group at entry

No difference between the groups at baseline

Appropriateness of duration of surveillance High risk

Only immediately postintervention data 2 years, no follow-up data reported

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Korpelainen 2006 Methods

Type of study: RCT

Participants

Number of participants randomised = 160 Losses: 68 women (81.0%) in the exercise group and 65 (85.5%) women in the control group completed the study Age: mean age 73 years Setting: Finland Inclusion: hip BMD value of more than 2 SD below the reference value Exclusion: use of a walking aid device other than a stick, bilateral hip joint replacement, unstable chronic illness, malignancy, medication known to affect bone density, severe cognitive impairment and involvement in other interventions

Interventions

Exercise group (COMB) (n = 84): jumping and balance exercises, including walking, knee bends, leg lifts, heel rises and drops, dancing, stamping, stair climbing and stepping up and down from benches Control Group (n = 76): usual activity Duration and intensity: 1hr sessions, 30 months Supervisor: physiotherapist Supervision:group and individual Setting: clinic and home

Outcomes

BMD Radius and hip (total hip, neck of femur, trochanter) During the 30-month follow-up, there were 88 falls in the exercise group and 101 falls in the control group (P = 0.10). The incidence of fall-related fractures was higher in the control group (n = 16) than in the exercise group (n = 6; P = 0.019). One woman in the control group had two fractures, and all other 20 women had one fracture

Notes

Compliance/adherence: Attendance at the exercise sessions averaged 78% during the first supervised 6-month period, 74% during the second supervised period and 73% during the last supervised 6 months. The average frequency of performing the home exercise programme was three times per week Adverse events: Three women in the exercise group experienced musculoskeletal problems that required minor modifications in the training regimen 5% level would require 64 women in each group to give an 80% power to detect a 0.02 g/cm2 difference in the primary outcome (femoral neck, trochanter and total hip BMD with an SD of 0.04 g/cm2 ) between the groups

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

Computer-generated random numbers

Allocation concealment (selection bias)

Randomisation provided by a technical assistant not involved in the conduction of the trial

Low risk

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Korpelainen 2006

(Continued)

Incomplete outcome data (attrition bias) All outcomes

Low risk

Data were analysed on an intention-to-treat basis, and any missing follow-up data was replaced with the last known value even if this was the baseline value

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Low risk

Operators were unaware of the women’s trial status

Comparability of exercise and control Low risk group at entry

No significant difference between the groups at baseline

Appropriateness of duration of surveillance Low risk

Immediately postintervention data 30 months, with follow-up data reported mean 7.1 years

Lau 1992 Methods

RCT

Participants

Number of participants randomised = 50 Losses:10 Age: 62-92 years Setting: China (Hong Kong) Inclusion: Female residents in hostel for elderly with mental function ≥ 6 on Hodkinson Scale Exclusion: metabolic bone disease; diabetes mellitus; previous hip fracture; blood creatinine level > 125 mUmol/l

Interventions

Calcium supplementation group (n = 12) received 800 mg calcium daily Exercise group and placebo (DWBLF) (n = 11): participants stepped up and down 23 cm high block 100 times then exercised upper trunk while standing for 15 minutes Exercise group and calcium supplementation (DWBLF) (n = 15): participants exercised as above and received 800 mg calcium per day Control Group (n = 12): received placebo tablet daily Duration and intensity: 4 times per week for 10 months. Submaximal exertion effort Supervisor: research nurse Supervision: throughout study Setting: not recorded

Outcomes

% change in BMD hip (neck of femur, Wards triangle) and lumbar spine

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Lau 1992

(Continued)

Notes

Compliance/adherence: not recorded Adverse events:epigastric discomfort (n = 1), and diarrhoea (n = 1) from calcium supplement

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

Random permuted blocks

Allocation concealment (selection bias)

Low risk

List prepared in advance and independent of sequence of entry

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

’As-treated’ analysis done drop-outs mentioned but unclear as to which groups

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’ but exercise is difficult to blind

Blinding (assessor)

Unclear risk

Serial BMD measures were computerised and largely automatic however the operator referred to copies of the first image in subsequent measurements

Comparability of exercise and control Low risk group at entry

No significant differences observed in baseline characteristics

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 10 months, no follow-up data recorded

Lord 1996 Methods

RCT

Participants

Number of participants randomised = 179 Losses: 32 from exercise group, 19 from control group Age: 60-85 yrs (mean 71.6; SD 5.3) Setting: Australia Inclusion: women who had participated in a previous falls and fractures study, living independently in the community Exclusion: illness or immobility; hospitalisation; medial conditions of neuromuscular, skeletal or cardiovascular system that precluded participation in exercise programme; non English speaking; participating in exercise classes of equivalent intensity to study intervention

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Lord 1996

(Continued)

Interventions

Exercise group (DWBLF) (n = 90): exercise: 5 warm up period: 35 min conditioning period (aerobic exercise, activities for balance, hand-eye and foot-eye coordination and stretching exercises); stretching period 15 min; relaxation 15 minutes Control Group (n = 89 ): no organised activity Duration and intensity:1 hour exercise classes twice weekly for four 10-12 week sessions for 12 months Supervisor: 3 trained instructors Supervision: at each class Setting: community exercise class

Outcomes

BMD, Lumbar spine, femoral neck, trochanter

Notes

Compliance/adherence: 59.8 (72.9%) 53 participants attended 50 or more classes Adverse events: none

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Complex randomisation procedure, but unclear how randomisation carried out

Allocation concealment (selection bias)

Low risk

Randomisation conducted prior to recruitment

Incomplete outcome data (attrition bias) All outcomes

Low risk

All initial participants accounted for

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’ but exercise is difficult to blind

Blinding (assessor)

Unclear risk

Not recorded

Comparability of exercise and control Low risk group at entry

No significant differences between groups at entry

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 12 months, no follow-up data reported

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Maddalozzo 2007 Methods

Type of study: RCT

Participants

Number of participants randomised = 141 Losses: retention rates 83% NHRT plus exercise, 89% HRT plus exercise; 91% HRT no exercise; and 82% control group Age: 52.1± 3.0 years Setting: USA Inclusion: women who had experienced the menopause within the previous 0-36 months from the time of baseline testing as determined retrospectively from questionnaire reports; (2) no menstrual cycles within the previous 12 months without being pregnant, but not longer than 36 months (based on questionnaire recall phone screening interview); (3) follicle-stimulating hormone levels ≥ 40 mIU/mL (obtained from the subjects physician) ; (4) body mass index (19-30 kg m−2), (5) 36 months or less of being diagnosed as being postmenopausal by their general physician; and (6) either taking HRT 0.625 mg conjugated equine oestrogen, (Premarin®) or non HRT use Exclusion: non-HRT users who had taken HRT for 12 consecutive months prior to applying to the study; (2) hypertension; (3) metabolic disease that may affect bone or muscle metabolism (including diabetes and thyroid disease); (4) statin medications for hypercholesterolaemia), multiple sclerosis; and (4) osteoarthritis or other musculoskeletal disorders that prevented participation

Interventions

Non HRT Exercise group (DWBHF) (n = 35): free weight back squat and free weight dead lift exercises repetitions at a speed of 1-2 sets for the concentric (lifting) and 2-3 sets for the eccentric (lowering) phases. Two warm-up sets of 10-12 repetitions at 50% of 1RM then 3 working sets at 60-75% of 1 RM (set 1 = 8 reps; set 2 = 10 reps; and set 3 = 12 reps) Non HRT Control Group (n = 34) HRT exercise group (DWBHF) (n = 37): as Non HRT Exercise group HRT Control Group (n = 35) Duration and intensity: 50 mins 2 x week for 52 weeks Supervisor: personal trainer Supervision: individual Setting: gym

Outcomes

BMD DXA lumbar spine (L1-L4), proximal femur (total hip, femoral neck, and greater trochanter) and whole body composition

Notes

Compliance/adherence: non-HRT plus exercise (84.7±12.8%) and HRT plus exercise group (86.2±11.4%) Adverse events: none reported Desired power ≥ 0.8, alpha = 0.05, and an expected difference between groups of 4% increase in muscle mass and a 1% increase in spine BMD, 25 subjects per group were needed

Risk of bias Bias

Authors’ judgement

Support for judgement

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Maddalozzo 2007

(Continued)

Random sequence generation (selection Unclear risk bias)

Self selected as either HRT or non-HRT replaced then randomised. Randomisation mentioned but insufficient information to permit judgement of ’high risk’ or ’low risk’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

’As-treated’ analysis done drop-outs mentioned but unclear as to which groups

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Unclear risk

Not reported

Comparability of exercise and control Low risk group at entry

No significant differences were observed at baseline on any variable except for spine BMD between HRT and non-HRT groups

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 52 weeks, no followup data reported

Martin 1993 Methods

RCT

Participants

Number of participants randomised = 76 Losses: 21, control n = 5, 30 min group n = 7, 45 min group n = 9 Age:49 - 66 years Setting: Florida USA Inclusion: women at least 12 months postmenopause; non-smoking; white (mainly European descent); no medical or orthopaedic contraindications to exercise; no use of medication known to interfere with calcium metabolism in preceding 12 months; no actively participation in aerobic or strength training programmes in preceding 12 months; no history of intolerance to dairy products; willing to take calcium and vitamin D supplementation; no bony vertebral abnormalities of lumbar or thoracic spine on xray; willing to accept randomisation Exclusion: not recorded

Interventions

All groups received calcium and vitamin D supplementation Exercise group 1 (DWBLF) (n = 27): 30 minute group. Start and end with 3-5 min of warm up to 60% of max heart rate. Then treadmill to 7% grade (inclination) and to 70% max heart rate in the first 2-4 weeks, and after to 85% (gradually) for 30 minutes in total Exercise group 2 (DWBLF) (n = 25): start and end with 3-5 min of warm up to 60%

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Martin 1993

(Continued)

of max heart rate. Then treadmill to 7% grade (inclination) and to 70% max heart rate in the first 2-4 weeks, and after to 85% (gradually) for 45 minutes in total Control Group (n = 19): calcium and vit D, no exercise Duration and intensity: 3 times a week for 1 year Supervisor: not recorded Supervision: not recorded Setting: not recorded Outcomes

BMD Lumbar, Proximal forearm, Distal forearm, Body Mass

Notes

Compliance/adherence: Group 1: 77.5 - 79.2 %, Group 2: 85.2 - 82.4% at 0 -6 and 6 - 12 months Adverse events: none reported

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation reported but insufficient information about the sequence generation process to permit judgement of ’high risk’ or ’low risk’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

’As-treated’ analysis done, drop-outs mentioned but different across the groups

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’ but exercise is difficult to blind

Blinding (assessor)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Comparability of exercise and control Low risk group at entry

No significant differences observed in baseline characteristics

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 12 months no follow-up data reported

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Metcalfe 2001 Methods

Type of study: RCT

Participants

Number of participants randomised = 301 (266 completed) Losses: 35 Age: 40-66 average 55.6 years Setting: USA Inclusion: postmenopausal women, sedentary, non smoking, no history of fracture or osteoporosis Exclusion: not reported

Interventions

Calcium tablets administered to both groups (800 mg per day) Non HRT Exercise group (COMB) (n = 177) warm up (5/10 min), progressive weight bearing (25 min) skipping, jogging, jumping, stair climbing with weighted vests. Resistance exercises with large muscle groups (20 min) 70-80% 1RM Resistance exercises with small muscle groups (10 min), Abdominal strengthening (5 min), Stretching and balance (5 min) Non HRT Control Group (n = 124): usual activity HRT Exercise group (COMB) (n =) : as exercise above HRT control group (n =): usual activity Duration and intensity: 60-75 minute session 3 non consecutive days per week for 12 months Supervisor: trainer with BSc MSc in exercise science or related field, certification by nationally recognised fitness and strength training organisation, and specifically trained in BEST programme by physical therapist Supervision: ratio of trainers to participants was 1:5 Setting: community fitness facility

Outcomes

BMD spine and hip using dual energy -ray absorptiometry Muscle strength

Notes

Compliance/adherence: 35 of exercise group dropped out. Retention rate 80.2% adherence to programme > 70.4% Adverse events: none reported

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation mentioned but insufficient information to permit judgement of ’high risk’ or ’low risk’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Low risk

Losses accounted for in exercise group

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

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Metcalfe 2001

(Continued)

Other bias

High risk

Exercise group appeared to have more support with incentive programmes, social interaction and mentoring from trainers

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Comparability of exercise and control Unclear risk group at entry

No data provided to compare group demographics

Appropriateness of duration of surveillance Low risk

Immediately postintervention data at 12 months, 4 year followup data reported

Nelson 1994 Methods

RCT

Participants

Number of participants randomised = 40 Losses: 1 participant from exercise group (suffered MI on holiday during first month of study) Age: 50-70 yrs Setting: USA Inclusion: at least 5 years postmenopausal; < 70 years of age; not participating in regular exercise programme (no strength training and < 20 mins of aerobic exercise twice per week); weighing less than 130% of ideal body weight; non-smoking; no more than 1 crush fracture of spine; no history of other osteoporotic fractures; and had not taken oestrogen or other medications known to affect bone for at least 12 months. Exclusion: not recorded

Interventions

Exercise group (NWBHF)(n = 21): 45 min sessions, 3 sets of eight repetition: high intensity strength training (concentric and eccentric contractions: hip extension, knee extension, lateral pull down, back extension, abdominal flexion using pneumatic resistance machine) Control Group (n = 19): they were asked to maintain their current level of physical activity during the year Duration and intensity: 52 weeks (2 weeks off for vacation), 2 times per week, with at least 1 day of rest between sessions Supervisor: exercise trainer Supervision: no more than two participant to each trainer Setting: not recorded

Outcomes

BMD (lumbar spine), femoral neck, Total Body (BMC)

Notes

Compliance/adherence: attendance averaged 87.5% +/- 1.8% Adverse events: 7 participants suffered transient musculoskeletal pain requiring minor modification of training regimen, but completed programme

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Nelson 1994

(Continued)

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation reported but insufficient information about the sequence generation process to permit judgement of ’high risk’ or ’low risk’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Low risk

’As-treated’ analysis done drop-outs mentioned but unclear as to which groups

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

Comparability of exercise and control Low risk group at entry Appropriateness of duration of surveillance High risk

Newstead 2004 Methods

Type of study: RCT

Participants

Number of participants randomised = 53 Losses: 7 ( 2 exercise, 5 control) Age: 50-65 years Setting: USA Inclusion: no co-morbidity e.g. diabetes, CHD, PVD, pulmonary or orthopaedic dysfunctions; not taking alendronate medication etc.; no current exercise programme; no history of osteoporotic fractures; BMI 21-31; on HRT if postmenopausal for >5 years. BMD T-score > -1.5 SD at hip and lumbar spine Exclusion: not reported

Interventions

Exercise group jumping (DWBHF)(n = 25): progressive multidirectional jumping, increasing jump heights and repetitions (max 200) Control Group (n = 28): usual activity Duration and intensity: 3 sessions per week for 12 months Supervisor: physical therapist Supervision: group 2x week, individual 1 x week Setting: gym

Outcomes

BMD femoral neck, total hip, lumbar spine

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Newstead 2004

(Continued)

Notes

Compliance/adherence: average 82% at month 6 and 75% month 12 Adverse events: none reported

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation mentioned but insufficient information to permit judgement of ’high risk’ or ’low risk’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

’As-treated’ analysis done drop-outs mentioned but unclear as to which groups

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Unclear risk

Not reported

Comparability of exercise and control Unclear risk group at entry

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Appropriateness of duration of surveillance High risk

Only immediately postintervention data 12 months, no followup data reported

Papaioannou 2003 Methods

Type of study: RCT

Participants

Number of participants randomised = 74 Losses: 14 lost at 6/12 (n = 60), 3 lost at 12/12 (n = 57) Age: mean age 71.6 (SD = 7.33) exercise group, 72.2 (SD = 7.98) in control. No significant differences in drop outs between groups Setting: Canada Inclusion: postmenopausal women 60yr + with osteoporosis (lumbar BMD >= 2.5 SD below young adult mean) and at least one vertebral fracture Exclusion: vertebral fracture within last 3 months; secondary causes of bone loss; other diagnosis for back pain; resting heart rate > 100 beats per min and uncontrolled hypertension; unable to stand independently for 3 min

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Papaioannou 2003

(Continued)

Interventions

Exercise group (COMB) (n = 37): exercise programme detailed in manual with diagrams, comprised stretching, strength training upper and lower limbs and aerobics Control Group (n = 37): Duration and intensity: 60 minutes of exercise over the course of the day, 3 days per week, with 1 rest day between for 12 months Supervisor: exercise Therapist. No further details Supervision:exercise group - monthly visits for first 6/12 with programme review. Followup call every 2 weeks to 12 months. Control - telephone contact by exercise therapist every month for 12 months Setting: home

Outcomes

DXA BMD lumbar spine (L2-4) femoral neck at baseline and 12 months

Notes

Compliance/adherence: defined as completing 3 sessions per week at least 80% of weeks. 62% participant’s adherent Adverse events: not reported No data reported

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation mentioned but insufficient information to permit judgement of ’Yes’ or ’No’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

No data presented for BMD other than no differences over 12 months between the groups

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Low risk

Research assistant and BMD investigator blinded

Comparability of exercise and control Low risk group at entry

Baseline variables not significantly different between groups

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 12 months, no follow-up data reported

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Preisinger 1995 Methods

RCT

Participants

Number of participants randomised = 146 Losses: not reported Age: 45-75 yrs Setting: Australia Inclusion: caucasian; 45-75 yrs of age; postmenopausal at least 1 year; did not suffer from malabsorption or other chronic diseases; non smoking; not taking oestrogen, other steroid hormones, anticonvulsants or thiazide diuretics; sedentary lifestyle; and normal blood results from described list. Exclusion: retrospective exclusion of women not attending tests or who commenced drug treatment for osteoporosis during follow-up period

Interventions

Exercise group (DWBLF) (n = 82): 1a (n = 39): warm up of brisk walking, modest jogging, arm swings and moderate skill exercises, stretching exercises hip and leg muscles, and complex resisted exercises to train movement patterns (diagonal or diagonal spiral movements) using elastic bands and gymnastic balls 1b (n = 43): stopped exercise treatment, performed it irregularly or less than 1 h per week Control Group (n = 64): no therapy Duration and intensity: at 3 times per week for 20 mins. Resisted exercises described as using considerable energy Supervisor: qualified therapist Supervision: 20 times over initial 10 week period, then 5 times every subsequent six months Setting: not recorded

Outcomes

BMD, SPA, Radium, Proximal

Notes

Compliance/adherence: 48% performed exercises regularly for the prescribed time Exercise group split retrospectively based on interviews and review of records at followup visit to 1a, 1b Adverse events: none reported No baseline data for lumbar spine and femoral neck presented to enable % change to be calculated

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation mentioned but insufficient information to permit judgement of ’Yes’ or ’No’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’Yes’ or ’No’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

Insufficient reporting of drop-outs from beginning of the study

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Preisinger 1995

(Continued)

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’Yes’ or ’No’

Other bias

Unclear risk

Poorly reported study - difficult to assess potential biases

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Low risk

Assessments were made by same investigator who was unaware of BMD measurements

Comparability of exercise and control Low risk group at entry

No significant differences between groups at entry

Appropriateness of duration of surveillance Low risk

Immediately postintervention and six monthly follow-up over ten year period

Prince 1991 Methods

RCT

Participants

Number of participants randomised = 120 Losses: 17, exercise group n = 6, exercise calcium group n = 3, exercise oestrogen group n=8 Age: mean 56±4 yrs Setting: Australia Inclusion: women with low forearm bone density; > 43 years of age; postmenopausal for 1-10 years; without hypertension or chronic diseases; not taking oestrogen, steroid hormones, anticonvulsants or thiazide diuretic drugs Exclusion: women with bone density not more than 1SD below mean for premenopausal women. Control group was randomly assigned from this group

Interventions

Exercise + placebo group (DWBLF) (n = 41): weekly class consisting of 1 hour low impact aerobics of which 30% of time devoted to arm exercises. Twice weekly 30 min brisk walk Exercise + calcium supplementation (n = 39): a/a Exercise + oestrogen supplementation (n = 40); a/a Control Group (n = 40): no exercise or placebo Duration and intensity: 1 hour class x 1 per week, 30 mins brisk walking x 2 per week for 2 years Supervisor: trained physiotherapist Supervision: during exercise class only Setting: not recorded

Outcomes

BMD forearm measured every 3 months

Notes

Compliance/adherence: 56% exercise only group; 24% exercise + calcium group; 44% exercise = oestrogen group attended a minimum of 10 classes in any 12 week period Adverse events: flushing, breast tenderness, sleeplessness etc

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Prince 1991

(Continued)

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

Shuffling of sealed envelopes

Allocation concealment (selection bias)

Low risk

Only pharmacist knew assignments

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

Unclear why so many of the exercise groups dropped out or did not complete sufficient exercise classes

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’Yes’ or ’No’

Other bias

High risk

Drug company Upjohn Australia supplied medication and supported research

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Unclear risk

Insufficient information to permit judgement of ’Yes’ or ’No’

Comparability of exercise and control High risk group at entry

Control group had normal BMD, and had been postmenopausal for less time (5.8±2.6 v 4.5±2.1)

Appropriateness of duration of surveillance Low risk

Only immediately postintervention data at 2 years, no followup data recorded

Prince 1995 Methods

RCT

Participants

Number of participants randomised = 168 Losses: not recorded Age: 50-70 yrs Setting: Australia Inclusion: 50-70 yrs of age, > 10 yrs postmenopausal Exclusion: significant chronic diseases, had received oestrogen, other steroid hormones, anticonvulsants, thiazide diuretic drugs or medications that could influence calcium metabolism

Interventions

Exercise group + calcium (DWBLF) (n = 42): 2 x 1 hour supervised classes comprising weight bearing exercise (not specified) Calcium group (n = 42): no exercise Milk powder group (n = 42): no exercise Control Group (n = 42): placebo medication only Duration and intensity: 4 hours per week, at 60% of peak maximal heart rate for age for 2 years

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Prince 1995

(Continued)

Supervisor: not recorded Supervision: supervision during exercise class Setting: not stated Outcomes

BMD lumbar spine, hip, distal tibia/fibula at baseline, 6, 12 18 and 24 months

Notes

Compliance/adherence: 39% of exercise group exercised for 3 hours per week at 60% peak heart rate Adverse events: not reported

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

Block randomisation with sealed envelopes prior to study commencing

Allocation concealment (selection bias)

Low risk

Sealed envelopes

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

’As-treated’ analysis done no drop-outs mentioned and no indication of numbers in each group

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

High risk

Drug company supplied placebo and calcium tablets

Blinding (participant)

High risk

Not possible

Comparability of exercise and control Low risk group at entry Appropriateness of duration of surveillance High risk

Pruitt 1996 Methods

RCT

Participants

Number of participants randomised = 40 Losses: 14 Age: 65-82 years Setting: America Inclusion: Healthy caucasian women not currently taking HRT, or those on HRT for 1 year or more Exclusion: evidence of acute or uncontrolled chronic illness or conditions that would prevent participation in exercise class, vertebral compression fractures, disorders affecting bone metabolism

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Pruitt 1996

(Continued)

Interventions

Exercise group 1 (NWBHF) (n = 15): supervised exercise session comprising bench press, lateral pull down, military press, biceps curl, knee extension, knee flexion, hip abduction and adduction, leg press, back extension. 1 set 14 reps at 40% 1RM, 2 sets 7 reps at 80% 1RM Exercise group 2 (NWBLF) (n = 13): a/a 3 sets 12 reps at 40% 1RM Control Group (n = 12): no exercises Duration and intensity: 3 times per week for 12 months, lifting time 50 -55mins. 1RM tests administered every 2 weeks for first 3 months then every 3 weeks to adjust workload Supervisor: not recorded Supervision: every session Setting: Gym

Outcomes

BMD lumbar spine, hip (total hip, neck of femur, Wards triangle) at baseline and 12 months

Notes

Compliance/adherence: 65% Adverse events: aggravation of pre-existing back or knee condition (n = 2)

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation reported but insufficient information about the sequence generation process to permit judgement of ’high risk’ or ’low risk’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

’As-treated’ analysis done drop-outs mentioned but different across the groups

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’. One outlier whose spinal BMD was more than 4SD from group mean was not included in analysis

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Comparability of exercise and control Low risk group at entry

No significant differences observed in baseline characteristics

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 12 months, no follow-up data reported

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Revel 1993 Methods

RCT

Participants

Number of participants randomised = 78 Losses: 11 withdrew but were not lost to follow-up (treatment group n = 6, control group n = 5) Age: 54±3 yrs Setting: France Inclusion: recruited from pension fund membership. Healthy postmenopausal caucasian women, postmenopausal for between 1 - 12 years (mean = 6±3). Not on oestrogen or oestrogen like compounds, corticosteroids, fluoride salts, diphosphonate’s or calcitonin Exclusion: not reported

Interventions

Exercise group (NWBLF) (n = 39): performed 60 repetitions of active hip flexion in sitting with 5 kg sandbag on knee. Hip flexion limited to 30 degrees. Could be performed over 2 or 3 sessions Control Group (n = 39): deltoid training, no further details Duration and intensity: 1 year, 60 repetitions daily Supervisor: not recorded Supervision: exercises taught initially no further supervision recorded Setting: not recorded

Outcomes

TBMD L1/L4

Notes

Compliance/adherence: 55% fully completed the training programme. 5 participants withdrew as they found the study too constraining (treatment group n = 4, control n = 1) Adverse events: treatment group hip pain (n = 1), control group shoulder pain (n = 3, back pain (n = 1) Follow-up data not reported by group

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation mentioned but insufficient information to permit judgement of ’Yes’ or ’No’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’Yes’ or ’No’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

Outcome reported for all that completed the trial. Authors say they did an ITT analysis on all but 5 of the participants, but none of the tables have figures that match this number

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’Yes’ or ’No’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Not feasible for exercise programmes

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Revel 1993

(Continued)

Blinding (assessor)

Low risk

Radiologist who performed scans was blinded to randomisation result

Comparability of exercise and control Low risk group at entry

No significant differences observed in baseline characteristics

Appropriateness of duration of surveillance Low risk

Only immediately postintervention data at 12 months, followup data at 2 years postintervention reported

Rubin 2004 Methods

RCT

Participants

Number of participants randomised = 70 Losses: 6 (1 active, five placebo) withdrew within first 3/12 and were replaced by new subject in same treatment type Age: 47-64 years Setting: USA Inclusion: 3-8 years postmenopausal women, normal nutritional status, stable weight, estimated daily Ca intake ≥ 500 mg daily, capable of following protocol, body mass 45 kg-84 kg Exclusion: any pharmacological intervention for osteopenia within last 6 months, steroid use, current smoking status, consumption of excessive alcohol, evidence of osteomalacia, osteogenesis imperfect, GI disease, history of malignancy, and/or prolonged immobilisation of axial or appendicular skeleton within last 3 years, spondyloarthrosis, thyrotoxicosis, psychomotor disturbances, hyperparathyroidism, renal or hepatic disease, chronic diseases known to affect muscular system, and/or engaged in high impact activities at least 3 x per week

Interventions

Exercise group (DWBHF) (n = 33): vibration plate that vibrated at 30 Hz, 0.2 g peak to peak Control Group (n = 37): placebo device, protocol a/a Duration and intensity: 2 x 10 mins treatments per day separated by a minimum of hrs, 7 days per week for 1 year Supervisor: none Supervision: none Setting: home

Outcomes

BMD by DXA R & L femur, lumbar spine, distal 1/3 radius at baseline, 3, 6 and 12 months

Notes

Compliance/adherence: 37% completing study were at least 80% compliant (10 active, 7 placebo), 72% at least 60% compliant (19 active, 14 placebo) Adverse events: 1 person (placebo group) reported headache Data presented as % change but as a function of compliance > 80% with exercise and only mean values presented

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Rubin 2004

(Continued)

Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

Confidential randomised number sequence

Allocation concealment (selection bias)

Low risk

Generated by individual statistical consultant

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

Losses accounted for and analysis based on the 56 subjects who completed the study and were scanned at end of study

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’Yes’ or ’No’

Other bias

High risk

Research funded by inventors of device

Blinding (participant)

Low risk

Each device emitted same low frequency sound, all participants insulated from each other at home

Blinding (assessor)

Low risk

Randomised code broken on completion of study

Comparability of exercise and control High risk group at entry

Significant differences in body weight and BMI with placebo 5 kg heavier than exercise group (P = 0.03)

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 12 months, no follow-up data reported

Russo 2003 Methods

Type of study: RCT

Participants

Number of participants randomised = 33 Losses: 6 at randomisation, 3 at follow-up (1 control, 3 exercise) Age: mean (SE) exercise 60.7 (6.1) and control 61.4 (7.3) years Setting: USA Inclusion:1 year postmenopausal Exclusion: metabolic bone disorders, conditions contraindicating vibration training

Interventions

Exercise group (DWBHF) (n = 17): vibrating plates lateral oscillations 0.1-10 g. Progressive frequency up to 28 Hz up to 2 mins duration Control Group (n = 16): usual activity Duration and intensity: 2 x week for 6 months Supervisor: not stated Supervision: individual Setting: gym

Outcomes

BMD Trabecular volumetric bone density (mg/cm3) Cortical volumetric bone density (mg/cm3)

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Russo 2003

(Continued)

Notes

Compliance/adherence: not reported Adverse events: transient, slight lower leg itching and erythema, was also observed in 6 of 17 treated participants in this study. In no case, however, did this problem persist after the first 3 training sessions or cause interruption of the intervention. Knee pain of moderate intensity, without objective clinical signs, was observed in 2 overweight participants with pre-existing knee osteoarthritis. The pain subsided in both participants after a few days of rest

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

Randomisation by random number table

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

’As-treated’ analysis done drop-outs mentioned

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

Blinding (participant)

High risk

Comparability of exercise and control Low risk group at entry Appropriateness of duration of surveillance High risk

Sakai 2010 Methods

Type of study: RCT

Participants

Number of participants randomised = 94 Losses: 16 (3 exercise, 13 control) Age: mean age 68.3 years (61-85) Setting: Japan Inclusion: not stated Exclusion: not reported

Interventions

Exercise group (SWB) (n = 49): single leg standing Control Group (n = 45): usual activity Duration and intensity: 1 min per leg, 3 x per day for 6 months Supervisor: not stated

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Sakai 2010

(Continued)

Supervision: home exercise Setting: home Outcomes

BMD DEXA neck, trochanter, intertrochanter, Ward’s triangle

Notes

Compliance/adherence: not reported Adverse events: none reported

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

Randomisation by envelopes

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

’As-treated’ analysis done drop-outs mentioned but different across the groups

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Unclear risk

Not reported

Comparability of exercise and control Low risk group at entry

There were no significant differences in age, body height, body weight, body mass index and hip BMD between the 2 groups at baseline

Appropriateness of duration of surveillance High risk

Only immediately postintervention data 6 months, no followup data reported

Sinaki 1989 Methods

RCT

Participants

Number of participants randomised = 68 Losses: 3 from control group Age: 49-65 yrs Setting: America Inclusion: postmenopausal, 49-65 yrs of age, normal diet, without calcium, vitamin D or oestrogen supplementation. With normal ECG, blood results and urine analysis Exclusion: baseline BMD below 5th percentile of normal range

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Sinaki 1989

(Continued)

Interventions

Exercise group (NWBLF) (n = 34): back extension exercises performed in prone against resistance using backpack weighted to the equivalent of 30% of maximum isometric strength up to a maximum of 50 lb (22.7 kg) Control Group (n = 34): no active exercise Duration and intensity: 10 repetitions once a day, five days per week for 2 years Supervisor: not recorded Supervision: at outset only Setting: home

Outcomes

BMD lumbar spine at baseline, 6, 12, 18 and 24 months

Notes

Compliance/adherence: not recorded Adverse events: none recorded

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation reported but insufficient information about the sequence generation process to permit judgement of ’high risk’ or ’low risk’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Low risk

’As-treated’ analysis done, all 3 drop-outs were in control group

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Low risk

Assessor had no knowledge of group allocation

Comparability of exercise and control Unclear risk group at entry

No significant differences observed in baseline characteristics apart from total serum calcium and total thyroxine

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 2 years, no followup data reported

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Smidt 1992 Methods

RCT

Participants

Number of participants randomised = 55 Losses: 6; not clear which groups these came from Age: control group = 55.4±8, exercise group 56.6±6.6 Setting: America Inclusion: physician consent, no current medical history (within last 12 months) of low back pain, kidney, cardiac, neuromuscular or musculoskeletal dysfunction. No current involvement in weight training programme for abdominals or back extensors, no obesity that preclude ability to use trunk testing equipment, at least one year postmenopause Exclusion: not recorded

Interventions

Exercise group (NWBHF) (n = 22): 3 sets of 10 repetitions of sit ups, prone trunk extension and double leg flexion (i.e. 90 reps in total) at 70% of maximal strength test, increasing by 2-5% monthly depending on ability Control Group (n = 27): maintain current lifestyle Duration and intensity: 3 to 3 times per week for 12 months Supervisor: not recorded Supervision: at outset and once per month Setting: home

Outcomes

BMD lumbar spine L2-4, hip (neck of femur, trochanter) at baseline, 6 and 12 months

Notes

Compliance/adherence: 11 participants performed exercises 3 times per week, 9 exercised 2-3 times Adverse events: none recorded Bad luck with randomisation: control group turned out to be very physically active

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation mentioned but insufficient information to permit judgement of ’Yes’ or ’No’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’Yes’ or ’No’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

Insufficient information to permit judgement of ’Yes’ or ’No’

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’Yes’ or ’No’

Other bias

Low risk

The study appears to be free of other source of bias

Blinding (participant)

High risk

Not practical for exercise classes

Blinding (assessor)

Unclear risk

Not reported

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Smidt 1992

(Continued)

Comparability of exercise and control Low risk group at entry

No significant difference between groups at entry

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 12 months, no follow-up data reported

Tolomio 2009 Methods

Type of study: RCT

Participants

Number of participants randomised = 160 Losses: 17. 16 failed to attend first session, 1 did not return following first session, 6 did not attend BMD scanning. 23 lost in exercise group, 12 in control group Age: postmenopausal (no other information recorded) Setting: Italy Inclusion: Postmenopausal women with osteoporosis or osteopenia Exclusion: orthopaedic operations

Interventions

Exercise group (n = 81) (COMB): 15 minutes warm up: walking at reasonable pace, joint movement, balance exercises, stretches. 30 minutes diverse exercises depending on objective i.e. strength, balance or flexibility using weights, balls, theraband and steps. 15 minutes cool down as warm up but lighter Control Group (n = 79): no exercises Duration and intensity: 44 weeks - 60 minutes 3 x per week at gym for 11 weeks; 1x per week at gym; and 2x per week in thermal water (spa) for 17 weeks; then 3x per week home exercises Supervisor: unclear Supervision: not clear for first two stages of trial. Telephone checks with advice for home exercise programme Setting: gym; gym/spa; home

Outcomes

BMD femoral neck and total hip

Notes

Compliance/adherence: not reported Adverse events: none recorded Data converted to % change

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation mentioned but insufficient information to permit judgement of ’Yes’ or ’No’

Allocation concealment (selection bias)

Insufficient information to permit judgement of ’Yes’ or ’No’

Unclear risk

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Incomplete outcome data (attrition bias) All outcomes

Low risk

All participants accounted for including drop-outs

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’Yes’ or ’No’

Other bias

Unclear risk

Insufficient information to permit judgement of ’Yes’ or ’No’

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Unclear risk

Insufficient information to permit judgement of ’Yes’ or ’No’

Comparability of exercise and control Low risk group at entry

No significant difference between groups at entry

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 11 months, no follow-up data reported

Uusi-Rasi 2003 Methods

Type of study: RCT

Participants

Number of participants randomised = 164 Losses: 7 (5 exercise and 2 control) Age: exercise mean 53.3 (2.2), control 53.2 (2.1) years Setting: Finland Inclusion: 1-5 years postmenopause; no previous bone fractures; neither current nor previous use of oestrogen, corticosteroids, bisphosphonates, nor other drugs, nor illness affecting bone metabolism; no contraindication to exercise or alendronate; previous regular exercise less than two times a week; femoral neck BMD 0.650 g/cm2 and an FSH level greater than 30 IU/L Exclusion: less than 1 year or more than 5 years postmenopause; history of chronic illness; evidence of metabolic bone disease or use of bone-specific medications; concurrent serious medical conditions including sepsis or disseminated cancer; abnormalities of the oesophagus; inability to stand or sit upright for at least 30 min; hypersensitivity to any component of the study drug; and hypocalcaemia

Interventions

Non alendronate Exercise group (DWBHF) (n = 41): placebo plus warm-up, 20 min of multidirectional jumping exercises, 15 min of callisthenics (stretching and non impact exercises), and 10 min cool down. The programme was progressive peak forces varied between 2.1 and 5.6 times body weight Non alendronate Control Group (n = 41): placebo usual activity Alendronate exercise group (DWBHF) (n = 41): as exercise above Alendronate control group (n = 41): usual activity Duration and intensity: 1 hr 3 x week for 1 year Supervisor: experienced exercise leaders of the UKK Institute Supervision: group Setting: gym

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Outcomes

The bone mineral content (BMC, g) and areal bone mineral density (BMD, g/cm2 ) of the lumbar spine, right proximal femur (femoral neck and trochanter area of the femur) , and nondominant distal radius

Notes

Compliance/adherence: Mean (SD) compliance in the exercise group, defined as attendance in the training sessions, was 1.6 0.9 times per week Adverse events: 19 subjects from the exercise group consulted the attending physician (P.K.) due to musculoskeletal injuries or symptoms; 1 subject had an acute severe ankle sprain requiring surgical treatment. The rest were mild overuse symptoms; 1 subject with a mild knee distortion injury; 5 subjects with an overuse problem at the knee joint (3 with chondromalacia patellae and 2 with unspecific knee pain); 4 with an overuse problem at the foot (2 with an insertional tendinopathy of the Achilles tendon and 2 with unspecific foot pain); 2 with low back pain (1 sciatica, 1 unspecific); 2 with hip pain (1 trochanteric bursitis, 1 unspecific); 2 with shoulder pain (both supraspinatus tendinitis); and 2 with unspecific fibromyalgia (tension neck symptoms)

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation mentioned but insufficient information to permit judgement of ’high risk’ or ’low risk’

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Low risk

Intention-to-treat analysis

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’ but states double-blind

Blinding (assessor)

Low risk

Outcomes assessors blinded to treatment group allocation

Comparability of exercise and control Low risk group at entry

There were no clinically relevant differences between groups

Appropriateness of duration of surveillance Low risk

Immediately postintervention data 12 months and follow-up data at 15 months postintervention reported

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Verschueren 2004 Methods

Type of study: RCT

Participants

Number of participants randomised = 70 Losses: not reported Age: 58-74 years Setting: Belgium Inclusion: 60 and 70 years of age, non-institutionalised, and free from diseases or medications known to affect bone metabolism or muscle strength Exclusion: total body BMD T-score of less than -2.5

Interventions

Exercise group vibrating platform (DWBHF)(n = 25): static and dynamic knee-extensor exercises on the vibration platform, progressive exercise Exercise group resistance training (NWBHF)(n = 22): warm-up, resistance training programme for knee extensors on a leg extension and a leg press machine. Training programme was designed (ASCM) for individuals older than 60 years of age. Progressive resistance Control Group (n = 23): usual activity Duration and intensity: 72 training sessions within a 24-week period. Training frequency was three times a week Supervisor: not stated Supervision: individual and group for resistance training Setting: gym

Outcomes

BMD DEXA total hip, total body

Notes

Compliance/adherence: not reported Adverse events: none reported

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias)

Randomisation by computer-generated random numbers agematched women

Allocation concealment (selection bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Incomplete outcome data (attrition bias) All outcomes

Unclear risk

’As-treated’ analysis done, insufficient information to permit judgement of ’high risk’ or ’low risk’

Selective reporting (reporting bias)

Unclear risk

Insufficient information to permit judgement of ’high risk’ or ’low risk’

Other bias

Low risk

The study appears to be free of other sources of bias

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Low risk

Technician unaware of intervention type

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Comparability of exercise and control Low risk group at entry

No significant differences were observed at baseline between the experimental and the control groups in terms of age, weight, body mass, years since menopause, BMD, serum levels of osteocalcin and CTX, isometric and dynamic muscle strength, fat mass or lean body mass

Appropriateness of duration of surveillance High risk

Only immediately postintervention data, no follow-up data reported

Von Stengel 2009 Methods

Type of study:RCT

Participants

Number of participants randomised = 151 Losses: 16, group 1 n = 5, group 2 n = 7, control n = 4. All invited for final measurements, 11 did not attend; group 1 n = 1, group 2 n = 6, control n = 4 Age: 65-72 years Setting: Germany Inclusion: Over 65, postmenopausal Exclusion: relevant co-morbidity or drug treatment which could influence bone metabolism

Interventions

Exercise group (COMB) (n = 50): Low impact aerobics, strengthening exercises and balance Exercise group (COMB) (n = 50): Low impact aerobics, strengthening and balance exercise as above and vibration plate. Vibration between 25-35 Hz, intensity increased at 3 and 6 months Control Group (n = 51): gentle exercise and relaxation class x 1 per week Duration and intensity: 60 minutes 2x per week for 12 months Supervisor: not reported Supervision: not reported Setting: hospital

Outcomes

BMD total hip and spine, rate of falls

Notes

Compliance/adherence: not reported Adverse events: none recorded Selected exercise group with vibration plate for analysis. Data converted to % change

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Unclear risk bias)

Randomisation mentioned but insufficient information to permit judgement of ’Yes’ or ’No’

Allocation concealment (selection bias)

Insufficient information to permit judgement of ’Yes’ or ’No’

Unclear risk

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Von Stengel 2009

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Incomplete outcome data (attrition bias) All outcomes

Low risk

Losses explained and data analysed on intention-to-treat

Selective reporting (reporting bias)

Low risk

Reporting as per protocol

Other bias

Low risk

The study appears to free of other sources of bias

Blinding (participant)

High risk

Not possible

Blinding (assessor)

Unclear risk

Not reported

Comparability of exercise and control Low risk group at entry

No significant differences between groups at entry

Appropriateness of duration of surveillance High risk

Only immediately postintervention data at 12 months, no follow-up data reported

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Ay 2005

No BMD DEXA, only US measures

Bebenek 2010

Control group underwent low intensity exercise

Bemben 2010

Subjects were assigned to a group based on their availability to attend the scheduled training sessions

Cao 2009

No BMD DEXA, only US measures

De Matos 2009

Not RCT subjects, selected group

Engelke 2006

Not RCT subjects, selected group

Hans 2002

Not an RCT

Hawkins 2002

Participants allocated to groups based on proximity to laboratory

Heinonen 1996

Pre-menopausal participants

Kemmler 2003

Not an RCT

Kerr 1996

Participants were their own control, one side of body randomised to a different exercise type

Kerschan-Schindl 2000

Randomisation not mentioned, described as observational study

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(Continued)

Kohrt 1995

Controlled trial, not an RCT

Kontulainen 2004

Pre-menopausal participants

Kriska 1986

No BMD outcomes

Leichter 1989

Not an RCT or CCT (before/after study)

Lohman 1995

Pre-menopausal participants

Mayoux-Benhamou 1995

Duplicate publication, French version

Nelson 1991

No control group

Notelovitz 1991

Surgical menopause, no control group

Pruitt 1992

Not an RCT

Rikli 1990

Controlled trial, not an RCT

Ruan 2008

Not RCT

Shen 2009

No outcome measures for BMD, only bone formation biomarkers

Snow 2000

Original study not an RCT

Song 2010

Participants had osteoarthritis

Tolomio 2008

No BMD DEXA, only US measures

Uusi-Rasi 2005

Follow-up of peri-menopausal women

Villareal 2003

Not an RCT

White 1984

Not an RCT

Xu 2004

Not RCT

Yamazaki 2004

Not RCT. Group assignment according to the wish of the participants

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Characteristics of studies awaiting assessment [ordered by study ID] Ilona 2010 Methods

Type of study: RCT

Participants

Number of participants randomised = 46 Losses: not recorded Age: 43-65 years Setting: Romania Inclusion: postmenopausal women diagnosed with osteoporosis or osteopenia Exclusion: concurrent orthopaedic or neurological disorders

Interventions

Exercise group (NWBLF) (n = 23): exercise, diet (diary products and veg), medication (Fosamax, Ca supplements, Vit D) Control Group (n = 23 ): diet (dairy products and veg), medication (Fosamax, Ca supplements, Vit D) Exercise group and controls well matched Duration and intensity: twice per week, 1 hour for 12 months. 8 - 10 repetitions with 1 minute between sets initially, rising to 12-15 times higher by end of intervention period • Warm up 10 min, static stretches, walking, deep breathing, easy running • Strength exercise 40 min low load, high repetition exercise for upper limbs performed in sitting, and callisthenic in supine and standing • Cool down, 10 min (not reported) Supervisor: physiotherapist, experience not recorded Supervision: close physiotherapist surveillance Setting: not recorded ** paper classifies study as measuring the effect of high impact exercise but impact appears to occur only in warm up phase, clarification on the researchers definition of callisthenic exercise would be helpful

Outcomes

BMD , T score lumbar spine DEXA (L1 -4) baseline and 12 months

Notes

Compliance/adherence: not recorded Adverse events: not recorded

Karaarslan 2010 Methods

Type of study:

Participants

Number of participants randomised = Losses: Age: Setting: Inclusion: Exclusion:

Interventions

Exercise group (n =): Control Group (n = ): Duration and intensity: Supervisor: Supervision: Setting:

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Outcomes Notes

Compliance/adherence: Adverse events: awaiting full paper

Kemmler 2004a Methods

Type of study:

Participants

Number of participants randomised = Losses: Age: Setting: Inclusion: Exclusion:

Interventions

Exercise group (n =): Control Group (n = ): Duration and intensity: Supervisor: Supervision: Setting:

Outcomes Notes

Compliance/adherence: Adverse events: awaiting full paper

Characteristics of ongoing studies [ordered by study ID] Wayne 2010 Trial name or title

not known

Methods

Type of study: Pragmatic RCT

Participants

Number of participants randomised = 86 Losses: Age: 45-70 Setting: America Inclusion: women aged 45-70; postmenopausal > 12 months; BMD T scores of hip and/or spine between 1.0 and 2.5; does not exercise more than 5 days a week on average for more than 60 minutes per day Exclusion: osteoporotic (T-score < - 2.5) at any site or a fracture in last 2 years not caused by road traffic collision; prior or current use of: oestrogen or calcitonin (within last year); medication that increases risks of

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fracture (e.g. steroids, anti-convulsants, anticoagulants, lithium); medications that modify bone metabolism; use of calcium supplements above 1200-1500 mg; malignancies other than skin cancer; diagnosis of anorexia along with BMI < 17.5; conditions causing secondary osteoporosis; tobacco use in past year; physical or mental disabilities that preclude informed consent in participation; geographical or scheduling limitations that preclude weekly participation in exercise class and study; current regular practice of Tai Chi Interventions

Exercise group (DWBLF) (n =): Control Group (n = ): Duration and intensity: 9 months. Minimum 2 classes (60 min each session) and 2 additional practice sessions (min 30 min) per week in first month, then a minimum of 1 per week and 3 practice sessions for remaining 8 months Supervisor: classes led by junior instructor supervised by senior instructor Supervision: at class Setting: Tia Chi, school and home

Outcomes

BMD lumbar spine and proximal femur assessed by DEXA Compliance/adherence: Adverse events:

Starting date

Not recorded

Contact information

peter [email protected]

Notes

Registered with Clinical Trials.gov, ID number NCT01039012

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DATA AND ANALYSES

Comparison 1. Any exercise versus control

Outcome or subgroup title 1 Total number of fractures 2 Bone mineral density % change: spine 3 Bone mineral density % change: femoral neck 4 Bone mineral density % change: Ward’s triangle 5 Bone mineral density % change: hip 6 Bone mineral density % change: trochanter 7 Bone mineral content % change: spine 7.1 Immediately postintervention 7.2 Follow-up at 15 months post intervention 8 Bone mineral content % change: femoral neck 8.1 Immediately postintervention 8.2 Follow-up at 15 months postintervention

No. of studies

No. of participants

4 24

539 1441

Odds Ratio (M-H, Random, 95% CI) Mean Difference (IV, Fixed, 95% CI)

0.61 [0.23, 1.64] 0.85 [0.62, 1.07]

19

1338

Mean Difference (IV, Random, 95% CI)

-0.08 [-1.08, 0.92]

6

185

Mean Difference (IV, Fixed, 95% CI)

-2.67 [-4.06, -1.28]

13

863

Mean Difference (IV, Random, 95% CI)

0.41 [-0.64, 1.45]

10

815

Mean Difference (IV, Fixed, 95% CI)

1.03 [0.56, 1.49]

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1

Statistical method

Effect size

1

76

Mean Difference (IV, Fixed, 95% CI)

1.43 [-9.18, 12.04]

1

50

Mean Difference (IV, Fixed, 95% CI)

2.44 [-8.96, 13.84]

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1 1

76

Mean Difference (IV, Fixed, 95% CI)

0.0 [-9.11, 9.11]

1

51

Mean Difference (IV, Fixed, 95% CI)

2.98 [-7.41, 13.37]

Comparison 2. Static weight bearing exercise versus control

Outcome or subgroup title 1 Bone mineral density % change: hip

No. of studies

No. of participants

1

31

Statistical method Mean Difference (IV, Fixed, 95% CI)

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Effect size 2.42 [0.73, 4.10]

88

Comparison 3. Dynamic weight bearing exercise low force versus control

Outcome or subgroup title 1 Bone mineral density % change: spine 2 Bone mineral density % change: femoral neck 3 Bone mineral density % change: trochanter 4 Bone mineral density % change: Ward’s triangle 5 Bone mineral density % change: wrist 6 Bone mineral density mean regression slope % change: wrist 7 Fractures 7.1 Vertebral year 1 7.2 Vertebral year 2 7.3 Total number of fractures

No. of studies

No. of participants

7

519

Mean Difference (IV, Fixed, 95% CI)

0.87 [0.26, 1.48]

5

485

Mean Difference (IV, Random, 95% CI)

-1.20 [-4.45, 2.05]

2

241

Mean Difference (IV, Fixed, 95% CI)

0.39 [-0.59, 1.38]

1

23

Mean Difference (IV, Fixed, 95% CI)

-3.6 [-5.48, -1.72]

1

83

Mean Difference (IV, Fixed, 95% CI)

0.10 [-1.30, 1.50]

1

103

Mean Difference (IV, Fixed, 95% CI)

1.4 [0.85, 1.95]

2 2 1 2

229 97 229

Odds Ratio (M-H, Random, 95% CI) Odds Ratio (M-H, Random, 95% CI) Odds Ratio (M-H, Random, 95% CI) Odds Ratio (M-H, Random, 95% CI)

Subtotals only 0.54 [0.11, 2.65] 4.18 [0.45, 38.82] 0.92 [0.21, 3.96]

Statistical method

Effect size

Comparison 4. Dynamic weight bearing exercise high force versus control

Outcome or subgroup title 1 Bone mineral density % change: spine 2 Bone mineral density % change: hip 3 Bone mineral density % change: mid femur 4 Bone mineral density % change: proximal tibia 5 Calcium bone index % change: trunk and upper thighs 6 Bone mineral density % change: trochanter 7 Bone mineral density % change: femoral neck 8 Bone mineral content % change: spine 8.1 Immediately postintervention 8.2 Follow-up at 15 months postintervention

No. of studies

No. of participants

4

247

Mean Difference (IV, Fixed, 95% CI)

0.60 [-0.23, 1.44]

4

179

Mean Difference (IV, Fixed, 95% CI)

1.55 [1.41, 1.69]

1

23

Mean Difference (IV, Fixed, 95% CI)

0.12 [-4.84, 5.08]

1

23

Mean Difference (IV, Fixed, 95% CI)

3.31 [-20.22, 26.84]

1

32

Mean Difference (IV, Fixed, 95% CI)

5.3 [-7.50, 18.10]

2

188

Mean Difference (IV, Fixed, 95% CI)

1.23 [-0.01, 2.47]

3

237

Mean Difference (IV, Fixed, 95% CI)

1.06 [-0.32, 2.45]

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1

Statistical method

Effect size

1

76

Mean Difference (IV, Fixed, 95% CI)

1.43 [-9.18, 12.04]

1

50

Mean Difference (IV, Fixed, 95% CI)

2.44 [-8.96, 13.84]

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9 Bone mineral content % change: femoral neck 9.1 Immediately postintervention 9.2 Follow-up at 15 months postintervention 10 Bone mineral content % change: wrist 10.1 Immediately postintervention 10.2 Follow-up at 15 months postintervention 11 Bone mineral content % change: ankle 12 Bone mineral content % change: tibia 13 Bone mineral density % change: total body 14 Volumetric bone density % change: tibial trabecular 15 Volumetric bone density % change: tibial cortical 16 Fractures 16.1 Total number of fractures

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1

76

Mean Difference (IV, Fixed, 95% CI)

0.0 [-9.11, 9.11]

1

51

Mean Difference (IV, Fixed, 95% CI)

2.98 [-7.41, 13.37]

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1 1

76

Mean Difference (IV, Fixed, 95% CI)

-3.41 [-15.64, 8.82]

1

50

Mean Difference (IV, Fixed, 95% CI)

1

76

Mean Difference (IV, Fixed, 95% CI)

-0.70 [-14.96, 13. 56] 2.07 [-7.09, 11.23]

1

76

Mean Difference (IV, Fixed, 95% CI)

0.86 [-6.22, 7.94]

2

179

Mean Difference (IV, Fixed, 95% CI)

0.37 [-0.00, 0.75]

1

29

Mean Difference (IV, Fixed, 95% CI)

1

29

Mean Difference (IV, Fixed, 95% CI)

-1.15 [-20.30, 18. 00] 0.49 [-2.93, 3.91]

1 1

112

Odds Ratio (M-H, Random, 95% CI) Odds Ratio (M-H, Random, 95% CI)

Subtotals only 1.56 [0.16, 15.56]

Comparison 5. Non-weight bearing exercise low force versus control

Outcome or subgroup title 1 Bone mineral density % change: spine 2 Bone mineral density % change: total hip 3 Bone mineral density % change: femoral neck 4 Bone mineral density % change: Ward’s triangle 5 Bone mineral density % change: trochanter 6 Bone mineral density % change: total body

No. of studies

No. of participants

5

231

Mean Difference (IV, Fixed, 95% CI)

-0.17 [-1.13, 0.79]

3

99

Mean Difference (IV, Fixed, 95% CI)

-0.03 [-4.94, 4.89]

3

99

Mean Difference (IV, Fixed, 95% CI)

0.21 [-6.02, 6.45]

2

33

Mean Difference (IV, Fixed, 95% CI)

2.75 [-17.96, 23.47]

2

81

Mean Difference (IV, Fixed, 95% CI)

0.05 [-7.04, 7.14]

2

81

Mean Difference (IV, Fixed, 95% CI)

1.27 [-2.73, 5.27]

Statistical method

Exercise for preventing and treating osteoporosis in postmenopausal women (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Effect size

90

Comparison 6. Non-weight bearing exercise high force versus control

Outcome or subgroup title 1 Bone mineral density % change: spine 2 Bone mineral density % change: total hip 3 Bone mineral density % change: femoral neck 4 Bone mineral density % change: Ward’s triangle 5 Bone mineral density % change: trochanter 6 Bone mineral density % change: total body

No. of studies

No. of participants

8

246

Mean Difference (IV, Fixed, 95% CI)

0.86 [0.58, 1.13]

5

165

Mean Difference (IV, Fixed, 95% CI)

0.11 [-0.06, 0.29]

8

247

Mean Difference (IV, Fixed, 95% CI)

1.03 [0.24, 1.82]

4

108

Mean Difference (IV, Fixed, 95% CI)

-1.77 [-3.87, 0.33]

4

149

Mean Difference (IV, Fixed, 95% CI)

0.40 [-1.36, 2.17]

3

100

Mean Difference (IV, Fixed, 95% CI)

0.55 [-0.51, 1.62]

Statistical method

Effect size

Comparison 7. Combination versus control

Outcome or subgroup title 1 Bone mineral density % change: spine 1.1 immediately postintervention 1.2 Follow-up at 1 year 1.3 Follow-up at 5 years 2 Bone mineral density % change: total hip 3 Bone mineral density % change: trochanter 3.1 immediately postintervention 3.2 Follow-up at 5 years 4 Bone mineral density % change: total body 4.1 immediately postintervention 4.2 Follow-up at 5 years 5 Calcium bone index % change: trunk and upper thighs 6 Bone mineral density % change: neck of femur 6.1 immediately postintervention 6.2 Follow-up at 5 years

No. of studies

No. of participants

4

Statistical method

Effect size

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

4

258

Mean Difference (IV, Fixed, 95% CI)

3.22 [1.80, 4.64]

1 1 4

28 34 468

Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)

3.33 [1.13, 5.53] -1.60 [-5.64, 2.44] -1.07 [-1.58, -0.56]

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2 2

200

Mean Difference (IV, Fixed, 95% CI)

1.31 [0.69, 1.92]

1 2

34

Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)

-3.50 [-9.93, 2.93] Subtotals only

2

213

Mean Difference (IV, Fixed, 95% CI)

0.14 [-0.32, 0.60]

1 1

34 31

Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)

-0.70 [-2.19, 0.79] 9.04 [-5.13, 23.21]

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

3 3

325

Mean Difference (IV, Fixed, 95% CI)

0.45 [0.08, 0.82]

1

34

Mean Difference (IV, Fixed, 95% CI)

0.70 [-3.33, 4.73]

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7 Bone mineral density % change: Ward’s triangle 7.1 immediately postintervention 7.2 Follow-up at 5 years 8 Bone mineral density % change: arms 8.1 immediately postintervention 8.2 Follow-up at 5 years 9 Fractures 9.1 Total number of fractures

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1

40

Mean Difference (IV, Fixed, 95% CI)

8.38 [-7.27, 24.03]

1 1

34

Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)

-2.0 [-7.96, 3.96] Subtotals only

1

40

Mean Difference (IV, Fixed, 95% CI)

0.02 [-9.43, 9.47]

1 2 2

34

Mean Difference (IV, Fixed, 95% CI) Odds Ratio (M-H, Random, 95% CI) Odds Ratio (M-H, Random, 95% CI)

-0.60 [-3.65, 2.45] Subtotals only 0.33 [0.13, 0.85]

236

Comparison 8. Dynamic weight bearing exercise high force plus HRT versus HRT

Outcome or subgroup title 1 Bone mineral density % change: proximal tibia 2 Bone mineral density % change: hip 3 Bone mineral density % change: mid femur 4 Bone mineral density % change: spine 5 Bone mineral density % change: trochanter 6 Bone mineral density % change: femoral neck 7 Bone mineral density % change: total body

No. of studies

No. of participants

1

19

Mean Difference (IV, Fixed, 95% CI)

2

86

Mean Difference (IV, Fixed, 95% CI)

-2.33 [-21.77, 17. 11] 0.17 [-6.37, 6.72]

1

19

Mean Difference (IV, Fixed, 95% CI)

0.35 [-3.33, 4.03]

2

203

Mean Difference (IV, Fixed, 95% CI)

-0.14 [-0.87, 0.60]

2

203

Mean Difference (IV, Fixed, 95% CI)

1.86 [0.60, 3.13]

2

203

Mean Difference (IV, Fixed, 95% CI)

0.59 [-0.50, 1.67]

1

136

Mean Difference (IV, Fixed, 95% CI)

0.01 [-0.32, 0.34]

Statistical method

Effect size

Comparison 9. Non-weight bearing exercise high force plus bisphosphonates versus bisphosphonates

Outcome or subgroup title 1 Bone mineral density % change: spine 2 Bone mineral density % change: hip 3 Bone mineral density % change: femoral neck 4 Bone mineral density % change: trochanter

No. of studies

No. of participants

1

26

Mean Difference (IV, Fixed, 95% CI)

-3.4 [-5.79, -1.01]

1

26

Mean Difference (IV, Fixed, 95% CI)

-0.1 [-1.90, 1.70]

1

26

Mean Difference (IV, Fixed, 95% CI)

-0.3 [-2.52, 1.92]

1

26

Mean Difference (IV, Fixed, 95% CI)

-0.5 [-2.74, 1.74]

Statistical method

Exercise for preventing and treating osteoporosis in postmenopausal women (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Effect size

92

5 Bone mineral density % change: Ward’s triangle 6 Bone mineral density % change: total body 7 Bone mineral content % change: total body

1

26

Mean Difference (IV, Fixed, 95% CI)

-1.5 [-6.52, 3.52]

1

26

Mean Difference (IV, Fixed, 95% CI)

-0.30 [-1.96, 1.36]

1

26

Mean Difference (IV, Fixed, 95% CI)

-1.5 [-3.35, 0.35]

Comparison 10. Dynamic weight bearing exercise high force plus bisphosphonates versus bisphosphonates

Outcome or subgroup title 1 Bone mineral content % change: spine 1.1 immediately postintervention 1.2 Follow-up at 15 months postintervention 2 Bone mineral content % change: femoral neck 2.1 Immediately postintervention 2.2 Follow-up at 15 months postintervention 3 Bone mineral content % change: wrist 3.1 Immediately postintervention 3.2 Follow-up at 15 months postintervention 4 Bone mineral content % change: distal tibia 5 Bone mineral content % change: tibial shaft

No. of studies

No. of participants

2

Statistical method

Effect size

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2

126

Mean Difference (IV, Fixed, 95% CI)

0.93 [-7.70, 9.56]

1

51

Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)

-2.33 [-15.79, 11. 13] Subtotals only

1 1

76

Mean Difference (IV, Fixed, 95% CI)

-0.65 [-10.81, 9.51]

1

51

Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)

-1.01 [-12.37, 10. 35] Subtotals only

1 1

76

Mean Difference (IV, Fixed, 95% CI)

0.52 [-13.99, 15.03]

1

50

Mean Difference (IV, Fixed, 95% CI)

1

76

Mean Difference (IV, Fixed, 95% CI)

-0.32 [-18.97, 18. 33] 0.18 [-8.33, 8.69]

1

76

Mean Difference (IV, Fixed, 95% CI)

0.4 [-6.31, 7.11]

Comparison 11. Non-weight bearing exercise high force plus antioxidants versus antioxidants

Outcome or subgroup title 1 Bone mineral density % change: spine 2 Bone mineral density % change: femoral neck

No. of studies

No. of participants

1

16

Mean Difference (IV, Fixed, 95% CI)

1

16

Mean Difference (IV, Fixed, 95% CI)

Statistical method

Exercise for preventing and treating osteoporosis in postmenopausal women (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Effect size -0.92 [-18.73, 16. 89] -2.24 [-21.61, 17. 13]

93

Comparison 12. Dynamic weight bearing exercise low force plus Ca2+ versus Ca2+

Outcome or subgroup title 1 Bone mineral density % change: femoral neck 2 Bone mineral density % change: spine 3 Bone mineral density % change: trochanter 4 Bone mineral density % change: distal tibia 5 Bone mineral density % change: Ward’s triangle

No. of studies

No. of participants

2

111

Mean Difference (IV, Random, 95% CI)

4.44 [-3.44, 12.32]

1

27

Mean Difference (IV, Fixed, 95% CI)

-1.02 [-1.36, -0.68]

2

111

Mean Difference (IV, Random, 95% CI)

4.51 [-2.00, 13.03]

1

84

Mean Difference (IV, Fixed, 95% CI)

0.60 [0.46, 0.74]

1

27

Mean Difference (IV, Fixed, 95% CI)

14.5 [10.05, 18.95]

Statistical method

Effect size

Comparison 13. Non-weight bearing exercise low force plus calcium versus calcium

Outcome or subgroup title 1 Bone mineral density % change: spine 2 Bone mineral density % change: total hip 3 Bone mineral density % change: femoral neck 4 Bone mineral density % change: trochanter 5 Bone mineral density % change: total body

No. of studies

No. of participants

1

66

Mean Difference (IV, Fixed, 95% CI)

0.33 [-4.98, 5.64]

1

66

Mean Difference (IV, Fixed, 95% CI)

-0.08 [-5.32, 5.16]

1

66

Mean Difference (IV, Fixed, 95% CI)

0.14 [-6.56, 6.84]

1

66

Mean Difference (IV, Fixed, 95% CI)

-0.01 [-7.41, 7.39]

1

66

Mean Difference (IV, Fixed, 95% CI)

1.50 [-3.24, 6.24]

Statistical method

Effect size

Comparison 14. Non-weight bearing exercise high force plus calcium versus calcium

Outcome or subgroup title 1 Bone mineral density % change: femoral neck 2 Bone mineral density % change: trochanter 3 Bone mineral density % change: total hip 4 Bone mineral density % change: spine

No. of studies

No. of participants

1

60

Mean Difference (IV, Fixed, 95% CI)

1.15 [-6.35, 8.65]

1

60

Mean Difference (IV, Fixed, 95% CI)

0.01 [-7.04, 7.06]

1

60

Mean Difference (IV, Fixed, 95% CI)

1.14 [-4.04, 6.32]

1

60

Mean Difference (IV, Fixed, 95% CI)

-0.64 [-6.33, 5.05]

Statistical method

Exercise for preventing and treating osteoporosis in postmenopausal women (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Effect size

94

5 Bone mineral density % change: total body

1

60

Mean Difference (IV, Fixed, 95% CI)

0.09 [-4.19, 4.37]

Comparison 15. Dynamic weight bearing exercise low force plus calcium/VitD versus calcium/VitD

Outcome or subgroup title

No. of studies

No. of participants

1

35

Mean Difference (IV, Fixed, 95% CI)

1.42 [-1.28, 4.12]

1

35

Mean Difference (IV, Fixed, 95% CI)

1.64 [-4.81, 8.09]

1 Bone mineral density % change: spine 2 Bone mineral density % change:wrist

Statistical method

Effect size

Analysis 1.1. Comparison 1 Any exercise versus control, Outcome 1 Total number of fractures. Review:

Exercise for preventing and treating osteoporosis in postmenopausal women

Comparison: 1 Any exercise versus control Outcome: 1 Total number of fractures

Study or subgroup

Exercise

Control

Odds Ratio MH,Random,95% CI

Weight

Odds Ratio MH,Random,95% CI

n/N

n/N

Chan 2004

1/67

3/65

14.5 %

0.31 [ 0.03, 3.09 ]

Ebrahim 1997

6/49

4/48

30.2 %

1.53 [ 0.40, 5.82 ]

4/112

1/38

15.2 %

1.37 [ 0.15, 12.65 ]

Korpelainen 2006

6/84

16/76

40.1 %

0.29 [ 0.11, 0.78 ]

Total (95% CI)

312

227

100.0 %

0.61 [ 0.23, 1.64 ]

Karinkanta 2007

Total events: 17 (Exercise), 24 (Control) Heterogeneity: Tau2 = 0.37; Chi2 = 4.77, df = 3 (P = 0.19); I2 =37% Test for overall effect: Z = 0.97 (P = 0.33) Test for subgroup differences: Not applicable

0.01

0.1

Favours exercise

1

10

100

Favours control

Exercise for preventing and treating osteoporosis in postmenopausal women (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

95

Analysis 1.2. Comparison 1 Any exercise versus control, Outcome 2 Bone mineral density % change: spine. Review:

Exercise for preventing and treating osteoporosis in postmenopausal women

Comparison: 1 Any exercise versus control Outcome: 2 Bone mineral density % change: spine

Study or subgroup

Exercise

Mean Difference

Control

Weight

N

Mean(SD)

N

Mean(SD)

Bemben 2000

17

0.64 (11.55)

8

-0.69 (12.3)

0.1 %

1.33 [ -8.81, 11.47 ]

Bergstrom 2008

48

-0.31 (11.3)

44

-0.69 (14.9)

0.2 %

0.38 [ -5.06, 5.82 ]

Bocalini 2009

15

-0.13 (0.35)

10

-0.98 (0.35)

66.9 %

0.85 [ 0.57, 1.13 ]

Bravo 1996

61

0.55 (24.2)

63

-1.29 (27.4)

0.1 %

1.84 [ -7.25, 10.93 ]

Chan 2004

54

0.1 (3.12)

49

-0.89 (4.01)

2.7 %

0.99 [ -0.41, 2.39 ]

Chilibeck 2002

10

-0.6 (3.6)

12

-0.1 (3.12)

0.6 %

-0.50 [ -3.35, 2.35 ]

8

0 (19.45)

7

-0.99 (23.11)

0.0 %

0.99 [ -20.80, 22.78 ]

Ebrahim 1997

49

-1.71 (20.12)

48

-1.81 (18.8)

0.1 %

0.10 [ -7.65, 7.85 ]

Englund 2005

21

13.09 (28.51)

19

1.05 (22.33)

0.0 %

12.04 [ -3.76, 27.84 ]

Going 2003

71

0 (2.59)

59

-0.56 (2.31)

7.4 %

0.56 [ -0.28, 1.40 ]

Grove 1992

10

1.75 (2.07)

5

-6.1 (16.7)

0.0 %

7.85 [ -6.84, 22.54 ]

Hatori 1993

12

1.1 (2.9)

12

-1.7 (2.8)

1.0 %

2.80 [ 0.52, 5.08 ]

Iwamoto 2001

15

4.42 (1.11)

20

1.01 (3.16)

2.4 %

3.41 [ 1.92, 4.90 ]

Kerr 2001

54

-0.15 (7.25)

36

-0.01 (11.88)

0.3 %

-0.14 [ -4.48, 4.20 ]

Lau 1992

11

-1.9 (0.99)

12

-2.5 (1.3)

5.9 %

0.60 [ -0.34, 1.54 ]

Lord 1996

68

1.07 (2.59)

70

0.36 (3.91)

4.3 %

0.71 [ -0.39, 1.81 ]

Maddalozzo 2007

29

0.21 (18.91)

29

-4.38 (15.66)

0.1 %

4.59 [ -4.35, 13.53 ]

Nelson 1994

20

1 (3.6)

19

-1.8 (3.5)

1.1 %

2.80 [ 0.57, 5.03 ]

Newstead 2004

23

0.99 (14)

26

0.97 (13.73)

0.1 %

0.02 [ -7.76, 7.80 ]

Pruitt 1996

14

0.6 (16.47)

11

0 (24.1)

0.0 %

0.60 [ -16.05, 17.25 ]

Revel 1993

34

4.73 (49.97)

33

0.41 (31.13)

0.0 %

4.32 [ -15.55, 24.19 ]

Sinaki 1989

34

-1.4 (1.8)

31

-1.2 (2.2)

5.4 %

-0.20 [ -1.18, 0.78 ]

Smidt 1992

22

-1.79 (3.68)

27

-2.35 (3.45)

1.3 %

0.56 [ -1.45, 2.57 ]

Von Stengel 2009

44

1.17 (23.25)

47

0.31 (24.75)

0.1 %

0.86 [ -9.00, 10.72 ]

Total (95% CI)

744

100.0 %

0.85 [ 0.62, 1.07 ]

Chuin 2009

IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI

697

Heterogeneity: Chi2 = 27.13, df = 23 (P = 0.25); I2 =15% Test for overall effect: Z = 7.23 (P < 0.00001) Test for subgroup differences: Not applicable

-4

-2

Favours control

Exercise for preventing and treating osteoporosis in postmenopausal women (Review) Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

0

2

4

Favours exercise

96

Analysis 1.3. Comparison 1 Any exercise versus control, Outcome 3 Bone mineral density % change: femoral neck. Review:

Exercise for preventing and treating osteoporosis in postmenopausal women

Comparison: 1 Any exercise versus control Outcome: 3 Bone mineral density % change: femoral neck

Study or subgroup

Exercise

Mean Difference

Control

Weight

N

Mean(SD)

N

Mean(SD)

Bemben 2000

17

0.37 (16.45)

8

-1.06 (21)

0.4 %

1.43 [ -15.09, 17.95 ]

Bocalini 2009

15

-0.09 (1.9)

10

-1.58 (0.36)

11.7 %

1.49 [ 0.50, 2.48 ]

Bravo 1996

61

0.27 (19.6)

63

-0.53 (20.8)

1.7 %

0.80 [ -6.31, 7.91 ]

Chan 2004

54

-0.94 (3.85)

49

-1.8 (3.52)

10.4 %

0.86 [ -0.56, 2.28 ]

Chilibeck 2002

10

-0.1 (2.85)

12

-0.4 (2.77)

7.6 %

0.30 [ -2.06, 2.66 ]

8

0 (12.43)

7

0 (10.24)

0.7 %

0.0 [ -11.48, 11.48 ]

Ebrahim 1997

49

-0.25 (16)

48

-2.75 (20.77)

1.6 %

2.50 [ -4.89, 9.89 ]

Englund 2005

21

0 (12.46)

19

0 (18.13)

1.0 %

0.0 [ -9.74, 9.74 ]

Going 2003

71

0.57 (4.14)

59

-0.47 (4.12)

10.4 %

1.04 [ -0.39, 2.47 ]

Kerr 2001

54

0.47 (9.11)

36

-0.11 (15.6)

2.5 %

0.58 [ -5.07, 6.23 ]

Korpelainen 2006

84

-0.59 (1.23)

76

-1.04 (1.16)

13.0 %

0.45 [ 0.08, 0.82 ]

Lau 1992

11

-6.6 (2.86)

12

-1.1 (0.54)

9.5 %

-5.50 [ -7.22, -3.78 ]

Lord 1996

68

1.52 (5.19)

70

3.12 (6.52)

8.8 %

-1.60 [ -3.56, 0.36 ]

Maddalozzo 2007

29

-1.46 (16.84)

29

-3.19 (17.03)

1.2 %

1.73 [ -6.99, 10.45 ]

Nelson 1994

20

0.9 (4.5)

19

2.5 (3.8)

7.0 %

-1.60 [ -4.21, 1.01 ]

Newstead 2004

23

0 (9.67)

26

-1.27 (17.9)

1.4 %

1.27 [ -6.66, 9.20 ]

Pruitt 1996

15

0.07 (18.12)

11

0.79 (16.3)

0.5 %

-0.72 [ -14.02, 12.58 ]

Smidt 1992

22

1.06 (4.02)

27

-0.25 (3.84)

8.0 %

1.31 [ -0.91, 3.53 ]

Tolomio 2009

58

0 (18.18)

67

-1.18 (14.56)

2.4 %

1.18 [ -4.65, 7.01 ]

100.0 %

-0.08 [ -1.08, 0.92 ]

Chuin 2009

Total (95% CI)

690

IV,Random,95% CI

Mean Difference IV,Random,95% CI

648

Heterogeneity: Tau2 = 1.96; Chi2 = 58.64, df = 18 (P