American Journal of Lifestyle Medicine

July • Aug 2009

Scott B. Going, PhD, and Monica Laudermilk

Osteoporosis and Strength Training Abstract: Osteoporosis is a major public health problem. Mechanical strain, imparted by muscle action and ground reaction forces, regulates bone size, shape, mineral mass, and density and subsequently bone strength. Thus, physical activity is critical for bone development, bone health, and fracture risk reduction. Animal studies, in which strain can be manipulated and measured directly, consistently show bone responds to high-strain magnitudes and rates, and only a few repetitions are needed to elicit a response. Extrapolation to humans suggests resistance exercise may be effective for osteoporosis prevention. Indeed, strength-trained athletes have significantly higher bone mass and density than athletes and nonathletes who do not engage in similar training. Prospective studies also support the benefits of resistance exercise demonstrating slowed bone loss and often an increase of 1% to 3% in regional bone mineral density, especially in women. Although more work is needed to define the optimal dose and the effects of nonmechanical factors (eg, nutritional, endocrine, body composition) on the response, the effects of resistance exercise on muscle mass and strength, balance, and agility, in addition to direct skeletal benefits, underscore its importance for osteoporosis, falls, and fracture prevention.

Keywords: osteoporosis; resistance training; exercise; bone; bone density; bone strength; children; women; men

O

steoporosis is a major public health problem that will likely escalate as the population ages. Osteoporosis is characterized by low bone mass and microarchitectural deterioration leading to a reduction in bone strength, resulting in an increased susceptibility to fracture.1 In the United States, its prevalence is projected to increase from 10 to 12 million individuals older than age 50 years to nearly 14 million individuals by

because they require hospitalization and are associated with significant pain, disability, and excess mortality. A reported 315 000 Americans age 45 years and older were admitted to hospitals with hip fractures in 2001.2 Sadly, after sustaining a hip fracture, 20% of people die within the first year,3 40% are unable to work independently, and 60% require long-term care.4 Vertebral fractures are also associated with significant disability and morbidity, including decreased function, back pain, loss of height and deformity, and a reduced quality of life. Moreover, there are data showing that following a vertebral

At any age, as much daily physical activity as the person can safely tolerate is recommended. 2020.2 In addition, an estimated 47 million individuals with osteopenia (low bone mass) are at risk for future osteoporosis.2 Current estimates suggest that 30% to 50% of women and 15% to 30% of men will suffer a fracture due to osteoporosis sometime in their lifetime.1 Approximately 1.5 million fractures occur in the United States each year. Fractures occur most frequently at the hip, spine, and distal forearm. Hip fractures are the most serious

fracture, there is a 2 to 3 times increased risk of a subsequent fracture of a different type and at least a 4-fold increase in risk of another vertebral fracture.5 The economic costs of osteoporotic fractures are enormous. In the United States alone, the estimated cost per year for osteoporotic-related fractures is about $17 billion,2 and the costs are projected to increase to approximately $45 billion over the next 10 years. Development of effective osteoporosis

DOI: 10.1177/1559827609334979. Manuscript received April 10, 2008; revised July 8, 2008; accepted August 12, 2008. From the Department of Nutritional Sciences, Center for Physical Activity and Nutrition, University of Arizona, Tucson. Address for correspondence: Scott B. Going, PhD, Department of Nutritional Sciences, Center for Physical Activity and Nutrition, University of Arizona, 1713 E University Blvd, Tucson, AZ 85721; e-mail: [email protected]. For reprints and permissions queries, please visit SAGE’s Web site at http://www.sagepub.com/journalsPermissions.nav. Copyright © 2009 The Author(s) 310 Downloaded from ajl.sagepub.com at PENNSYLVANIA STATE UNIV on September 16, 2016

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Characteristics of Effective Osteogenic Stimuli Mechanical strain imparted by muscle action is responsible for the development of the external size and shape of the bone and ultimately bone strength. The intrinsic relationship between muscle and bone has been described by the mechanostat theory, which holds that bone mass, size, and strength change predictably and correspondingly with increasing maximal muscle force during growth or in response to increased loading.6 Likewise, unloading leads to impaired muscle development and lower muscle strength, with subsequent negative effects on bone mass, size, and strength. In the normal “healthy” situation, the mechanostat paradigm predicts that bone strength is adapted to keep everyday peak strains within a safe range to prevent microdamage and fracture and to optimize bone structure to best suit its functional needs. Nonmechanical factors are also important. Mechanostat setpoints that act as thresholds for initiation or inhibition of bone modeling and remodeling are regulated by the endocrine environment, which, in turn, is affected by both exercise and nutrition. Exercise, for example, in addition to its direct effect through muscle action on bone, acts indirectly through its effect on endocrine regulation. Nutrition also acts indirectly, through

Figure 1. Theoretical changes in bone volume (or strength) as a function of mechanical usage. 1 = hypothetical curve for growing bone; 2 = “normal” conditions, mature bone; 3 = estrogen deficiency (eg, female menopause). MES, minimum effective strain. Mechanical Usage Windows

Trivial (inactivity)

–

Physiological (usual activity)

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Bone Volume Change

prevention strategies is clearly a public health imperative. Bone is a dynamic tissue that continually adapts to its functional demands to produce a structure that is strong enough to prevent fractures during typical activities. Animal and human studies have clearly shown the importance of regular physical activity for optimal skeletal growth during development and maintenance of mineral mass and density in adulthood, although the optimal mode and dose of exercise remain uncertain. This article reviews the rationale and evidence for the role of resistance exercise for maintaining skeletal health and preventing osteoporosis. Other benefits, such as improved lean mass, muscle strength, and agility, which may reduce falls and thus fracture risk, are also discussed.

S2

50-200µε Remodeling MES

S3

1500-2500µε Modeling MES

endocrine factors that act on muscle and bone and through changes in body and muscle masses, which may contribute to hormonal imbalances (eg, hypogonadalism), which subsequently alters the bone response to exercise.7-10 According to the mechanostat theory, the “switches” that turn bone modeling and remodeling on and off are regulated by bone deformation. Mechanical forces are needed to deform bone, and these forces are predominately created by muscle contractions and, in weight-bearing bones, by gravitational forces associated with body weight. The magnitude of deformation is determined by bone material properties, size, and architecture, as well as the force acting on it. Exercise training can increase muscle strength and subsequently subject the skeleton to higher contractile forces. Exercise may also increase muscle mass, thereby increasing the gravitational forces acting on the weight-bearing bones. The hypothetical relationship between bone deformation (measured as strain) and bone modeling and remodeling is illustrated in Figure 1. Although it is well recognized that strain is the critical input driving the mechanostat, the challenges of measuring deformation due to the invasive nature of such measurements

3000-4000µε ˜ 25,000µε Repair MES Fracture strain

preclude direct estimates of strain magnitudes and rates in humans under usual circumstances. Consequently, the description of the bone response to various mechanical stimuli has necessarily been derived from animal studies in which strain can be precisely manipulated and measured directly.11 The results of these studies almost uniformly describe an inverse relationship between strain magnitude (load) and cycle number (repetitions)12; that is, increasing magnitude within a safe range is a more effective stimulus than increasing frequency,13 and increased duration (increased number of loading cycles) of skeletal loading does not yield proportional increases in bone mass, as the system quickly saturates.14,15 The estimates of the minimal effective strains (microstrains) that define the mechanical usage “windows” in Figure 1 are not precisely known for humans. It is clear, however, that bone cells are less responsive to customary loading signals (eg, common daily activities) and more responsive to novel loads (eg, lifting heavier weights or jumping and landing activities), including novel strain magnitudes and rates. The curvilinear nature of the response suggests that the effect of inactivity is far greater than that of adding more “usual” activity because usual daily activity (the range between 311

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American Journal of Lifestyle Medicine

July • Aug 2009

sedentary and moderately intense activity) is characterized by a relatively modest dose-response slope. Thus, engaging in more walking for an already ambulatory person may have little effect on bone mass and strength, whereas adding a more vigorous stimulus, for even a few repetitions, likely has greater benefit. Figure 1 also illustrates the notion that nonmechanical factors, such as estrogen withdrawal in a woman, may alter the mechano-sensory setpoint for skeletal adaptation7-9 and that children and adolescents may respond better than adults. Thus, the response to a given stimulus may vary depending on the developmental stage, age, and endocrine or nutritional status of the participant. The mechanostat paradigm has been extrapolated to humans and used to design exercise regimens.15 The findings from animal studies suggest that resistance exercise may have particular benefit for bone health. Indeed, comparisons between strength-trained athletes, other athletes, and nonathletes support this notion by demonstrating significantly higher bone mass and density in weightlifters, rowers, and other athletes in sports who engage in significant resistance training.16-21 Cross-sectional studies, however, suffer from significant selection bias and cannot answer the question of whether resistance training improves skeletal status. Recognition of this fact has led to a number of prospective studies of the effects of resistance training on bone mineral content and density, and the remainder of this article focuses on findings from longitudinal trials. Several earlier reviews have been published, and for additional information and other views, the reader is referred to these articles.22-25 Children and Adolescents Childhood and adolescence, when bone is changing rapidly, may provide a unique opportunity for osteoporosis prevention by maximizing bone mineral accrual through strength training and other modes of physical activity. Indeed, studies of child and adolescent athletes and other active youth support the importance of physical activity for optimal bone development.25,26 The

recent development of low-radiation, 3-dimensional imaging techniques (eg, peripheral quantitative computed tomography), as well as speculation that lasting changes in bone geometry may occur as a result of activities eliciting moderate to high ground reaction forces, has encouraged studies of the effects of “impact” exercise on bone mass and geometry.27-32 Few studies of resistance training have been done in children and adolescents, apparently and perhaps somewhat surprisingly because of safety concerns,25 because with proper supervision, childsized equipment, and instruction, weight lifting is likely as safe as other athletic endeavors in which children regularly engage. The few prospective studies that have been done have given equivocal results. For example, Blimkie et al33 investigated the change in bone mineral density (BMD) and bone mineral content (BMC) in response to 26 weeks of a machine-assisted weight-training intervention (3 times per week, 4 sets of 12 reps for several muscle groups) in adolescent girls. After 26 weeks, there were no significant differences in BMD or BMC for exercise versus control participants at any of the sites that were measured. In contrast, Nichols et al34 reported a significant increase in femoral neck BMD in adolescent girls after 15 months of resistance training (3 times per week; each workout included different combinations of 15 exercises using free weights and machines). However, change in BMD at other sites was not significant. Given the varying results and the small number of published studies in children and adolescents, specific recommendations regarding strength training in youth are tentative at best. Nevertheless, the importance of physical activity during childhood and adolescence is certain, and further prospective studies of the potential benefits of resistance exercise for bone development in children and adolescents are clearly warranted. Women Most training studies have been performed in women because of the much higher prevalence of osteoporosis in

women and the critical importance of maintaining bone health in this population. Representative studies are summarized in Figures 2 and 3, which show results from randomized and nonrandomized controlled trials and studies with various intensities and durations of training. In some studies, participants also received nutritional supplements (eg, calcium, vitamin D) or hormone replacement. Despite differences in designs (randomized controlled trial [RCT] or controlled trial [CT]), exercise regimens, and cotreatments, the results are quite consistent in showing increases in BMC and BMD in premenopausal and postmenopausal women with resistance training of about 1% to 3% at clinically relevant sites. Not all studies report significant increases, in part due to small sample sizes and differences in intensity and duration of training. Longer duration studies tend to result in significant increases in bone variables more often than shorter duration studies, likely because of the physiologic limits of bone formation and remodeling. Also, increases in regional measurements, such as femur and lumbar spine, tend to be significant more often than total body measures (eg, total body BMC and BMD), which has led some investigators to speculate whether regional increases represent a site-specific redistribution of bone mineral rather than a total body increase in BMD.35 Not all studies have reported beneficial effects. Two studies in premenopausal women reported no effect or a negative impact on bone. Vuori et al36 found that unilateral resistance training did not have a significant impact on BMD or BMC in physically active young women except at the patella, although there was a trend toward increased BMD and BMC at several sites in the trained limb. In another study, lumbar spine BMD decreased in the exercise group completing an intensive weight-training program and remained unchanged in the control group.37 This study, however, is difficult to interpret because of a nonrandomized design and because the women in the control group had greater body weight and body fat than the exercise group, which is typically associated with higher BMD.

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Figure 2. Treatment effect of resistance training intervention on site-specific bone mineral density in pre- and postmenopausal women. (A) Femur trochanter. (B) Lumbar spine. BMD, bone mineral density; BMC, bone mineral content.

Percentage Change per Year in BMD or BMC

Panel A

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Heinonen 1996

Friedlander Bassey 1994 Pruitt 1995 1995

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Kerr 1996a Kerr 1996b Nelson 1994

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In one of the strongest studies, because of its design, Kerr et al38 compared highload, low-repetition (6-8 repetitions) against low-load, high-repetition (20 repetitions) resistance exercises in postmenopausal women. Each participant trained only one side of her body, and the BMD of the exercise side was compared to the BMD of the control (nonexercise) side. In this way, other factors that may affect the BMD response (eg, hormonal and nutritional factors) were controlled, as they would affect both sides of the body. In this study, trochanter BMD on

SnowHarter 1992

Sinaki 1989

Pruitt 1995

Nelson 1994

Notelovitz 1991

Middle-Aged and Older Adults (postmenopausal)

the exercise side increased, whereas the BMD of the nonexercise side declined. High-load, low-repetition exercise was effective at increasing BMD, whereas lowload, high-repetition exercise was not effective. In a second study, Kerr et al39 showed resistance training increased total hip and trochanter BMD by 1.6% after 1 year of training and maintained it virtually unchanged over a second year of training. Over the same period, a group that engaged in low-resistance and cycling exercises and the control group lost BMD, resulting in a net effect of 3.2%

at 2 years. In contrast, 2 studies in older women found no significant group differences in change in BMD when lowintensity resistance training was compared to high-intensity training.40,41 Whether younger or older women benefit more from resistance training remains unclear. The potential risk of highintensity strength training in older women who may have significant bone loss is a legitimate concern, and thus some studies have tested lower intensity programs that may not have provided an adequate osteogenic stimulus. Also, postmenopausal women, having low levels of circulating estrogens, may not respond as readily as premenopausal women to a given dose of exercise (Figure 1). Conversely, older women, because of changes in activity levels and patterns, may respond similarly or better to a given dose because it may be more novel compared to their usual daily activities. Finally, some evidence suggests individuals with lower initial BMD respond to training more so than individuals with higher BMD,25 but how the “principle” of initial values interacts with age is uncertain. Sorting out these possibilities is difficult. Few direct comparisons of the responses to a standard program exist, as it is unusual for investigators to include younger and older (or pre- and postmenopausal) women in the same study. Several meta-analyses of the effects of resistance training on bone in women have been published in recent years.42-46 Unlike narrative reviews,22,23 meta-analysis has the advantage of statistically combining results of studies and providing an overall estimate of the effects of exercise on bone. Meta-analysis is appropriate when studies addressing the same primary outcome take on different characteristics—for example, different study designs, different periods of follow-up, and different types of resistance training programs. Meta-analysis is especially useful when sample sizes of individual studies are small, and it provides an opportunity to test covariates that may influence results. Effect sizes from studies of resistance exercise included in recent meta-analyses are summarized in Figures 2 and 3. In Figure 2, effect sizes are 313

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American Journal of Lifestyle Medicine

July • Aug 2009

Figure 3. Effect size of resistance training intervention on site-specific bone mineral density in pre- and postmenopausal women. (A) Femur trochanter. (B) Lumbar spine. BMD, bone mineral density; BMC, bone mineral content. *P = .05. Panel A 2.84

Hedges and Olkin’s* Effect Size

3

2

1

0.73 0.26

0.16

0.15 0 –0.10 –0.38

–0.40 –1 Kelley 2001 Lau 1992

Pruitt 1992 Kelley 2001

Young Adults (premenopausal)

Nelson 1994

Nelson 1991

Bloomfield Kohrt 1995 1993

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Panel B

2 1 0.06 0.18 0.21

* * 1.14 * 0.95 1.02

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expressed as percent change, standardized to a year of intervention. Weighted (using inverse variance weighting)47 overall treatment effects for randomized controlled trials are consistent in showing that exercise prevented or reversed about 1% of bone loss per year in both lumbar spine and femoral neck in pre- and postmenopausal women.44 In Figure 3, effect sizes were calculated as the ratio of the difference in posttreatment means (exercise minus control) to the weighted standard deviation.48 Thus, an effect size greater than 0 indicates a positive effect of exercise on bone, whereas a smaller than 0 effect

size indicates a detrimental effect. Overall treatment effects of studies in Figure 3, if expressed as percent change, would range from about 1% to 2% at lumbar spine and femur neck. The nature of meta-analysis implies that the meta-analysis itself inherits the limitations that exist in the literature— that is, studies included in an analysis may differ in important ways (eg, in design, participant characteristics, exercise regimens, and cotreatments). Heterogeneity, a common problem in meta-analysis, may also be viewed as an opportunity because it is possible to test the effects of covariates that may influence the outcome of

interest. Kelley et al,43 for example, examined the effects of initial BMD, calcium intake, age, years postmenopausal, length and intensity of training, and compliance. No significant associations were observed. Similarly, in a meta-analysis on individual patient data in postmenopausal women in which the effect of exercise on lumbar spine BMD was assessed, no significant main effects or interactions were found for body weight and calcium and vitamin D intakes.45 Given the notion that estrogen levels may modify mechanosensory setpoints and the response to bone loading, it is somewhat surprising that few studies have examined the interaction of resistance training with hormone replacement therapy (HRT), although renewed concern about the side effects of HRT have undoubtedly curtailed these investigations.49 Based on the few studies that have been reported, the effect of resistance exercise on bone mass seems to be somewhat less than that of HRT, but both additive and independent effects of exercise and HRT have been observed in postmenopausal women.50-52 Kohrt et al53 have suggested that HRT is most effective at weight-bearing sites that have a high cancellous bone content and that exercise-induced gains in BMD are preserved after training stops in women who continue HRT.54 Bergström et al,55 in a pilot study, showed that both HRT and training can prevent the loss of spine BMD in perimenopausal women over 18 months, but the design did not allow examination of the interactions or potential additive effects of exercise and HRT. The findings from other studies, with somewhat different designs, support these results. However, all of these studies suffered from one or more limitations, including small sample sizes and limited power, nonrandomization, or mixed HRT regimens, which limited the results. The Bone, Estrogen, Strength Training (BEST) study was perhaps the largest study of the effects of HRT and resistance exercise in early, postmenopausal women.52 In this study, 320 women who were either undergoing HRT or not undergoing HRT were randomized within group to resistance training or usual activity. In

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BEST, BMD increased by 1% to 2% at hip and spine sites after 1 year of exercise and HRT. The increase in BMD was greatest in women who used HRT, although women who exercised without HRT also improved BMD compared to controls, who lost BMD as expected. The most consistent change was observed at the hip (trochanter) site. Women who lifted the most cumulative weight (greatest “dose” of exercise) over the training period increased BMD the most, suggesting a dose-response relationship.56 Moreover, women who continued to exercise for 4 years after the main trial continued to benefit,57 demonstrating the importance of resistance exercise during early menopause, when there is typically an accelerated bone loss. Bone strength, the ultimate predictor of fracture risk, is a function of both its material properties and macro-architectural features. In addition to conventional changes in BMD, local bone geometry and mass distribution may be influenced by exercise and HRT. Cheng et al58 showed that the combination of high-impact exercise and HRT increased tibia shaft bone mass in the antero-posterior direction, resulting in an increased density-weighted moment of inertia at the maximum axis (Imax) and a greater resistance to bending loads. Similar studies of changes in bone geometry with resistance training are important to do, as focusing on BMD alone may underestimate the ultimate impact on bone strength. The potential risks of HRT are important to note. Although HRT may have benefits for bone, recent randomized clinical trials have provided little evidence of cardio protection and even some evidence of harm with postmenopausal hormone therapy. For example, based on results from the Women’s Health Initiative, Manson et al49 concluded that estrogen plus progestin does not confer cardiac protection and may increase the risk of coronary heart disease among generally healthy postmenopausal women. They concluded HRT should not be prescribed for the treatment of heart disease. Men Observations of greater bone mass and density in male weightlifters and other

strength-trained athletes support the view that resistance training improves skeletal status in men.59 Far fewer prospective studies have been done in men than women, although the findings from exercise trials in men are generally similar to findings in women, showing that resistance exercise is safe and results in important musculoskeletal adaptations that offset declines that normally occur with aging. In perhaps the only prospective study with a direct comparison of men and women, Maddalozzo and Snow60 reported that 6 months of high-intensity (70%-90%, 1 repetition maximum [RM]) weight training increased lumbar spine BMD (1.9%) in men and not in women, whereas moderate-intensity (40%-60%, 1 RM) training resulted in no changes in either gender. Both high- and moderateintensity training increased trochanter BMD in men, but no hip sites were improved in women. Within-group (1-way) comparisons demonstrated significant increases in trochanter BMD (1.3% and 2.0%, respectively) in men and women and a decrease in femoral neck BMD (–1.8%). Sample sizes were small, and the study lacked a control group, and so the results must be interpreted cautiously. Kelley et al,61 in a relatively recent meta-analysis, reviewed studies of exercise and BMD in men published between 1966 and 1998. Following an exhaustive search of the literature, these authors found only 8 studies (randomized and nonrandomized) in men that had included a control group and a training program lasting at least 16 weeks, and only 4 of these studies examined the effects of resistance exercise62-64 or resistance and aerobic exercise.65 Sample sizes in these studies were small (n = 7-17), 3 of the 4 used nonrandomized designs, and the exercise programs were short duration (4-7 months). Effect sizes were of the same magnitude as those reported for women (Figures 2 and 3). Unfortunately, there were too few studies to assess the relative effectiveness of resistance exercise versus other modes. Based on all available studies, effect size changes are equivalent to an exercise-minus-control improvement in BMD of about 2%. When data were partitioned according to whether the

BMD sites assessed were specific to the sites loaded during exercise, effect sizes were somewhat larger and more likely to be significant, equaling exercise-minuscontrol increases of ~2.6% initial BMD or duration training. The overall poor quality of the designs and small number of studies limit these findings, and additional studies regarding the effectiveness of resistance exercise for improving BMD in men are warranted. Patient Populations A few investigations of the effects of resistance exercise on BMD in patients with medical conditions other than osteoporosis have been done. For example, Braith et al63 studied the effects of lumbar extension exercise and moderate-intensity lower body resistance exercise on regional BMD in middle-aged male heart transplant patients. Patients who exercised were able to restore BMD, whereas transplant recipients in the control group continued to lose bone. Similarly, a very recent study showed that resistance exercise in older, overweight adults with type 2 diabetes was effective in maintaining BMD during a weight loss program,66 which is sometimes associated with bone loss. These results suggest that resistance training may be an effective strategy for preventing secondary bone loss due to other medical conditions and interventions. Cotreatments Given the likely role of nonmechanical factors in the response to bone loading, combination therapies may have important benefits, either by promoting additive effects or by “potentiating” the response to a lower intensity, which may be safer for older individuals. There have been few studies of resistance training combined with pharmacotherapy, other than HRT.51,52,55 In one study, the effects of alendronate and weight-bearing exercise on bone in postmenopausal women were assessed,67 with results similar to outcomes from studies of HRT—that is, the effect of weight-bearing exercise on bone mass was somewhat less than alendronate. In a study of older men, Yarasheski et al68 315

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found no additional benefit of growth hormone with resistance exercise compared to exercise alone on whole-body and regional BMD, although the intervention lasted only 4 months. Similar studies with pharmacotherapy are needed as the combination may have benefits for bone quality as well as mass and density, which would add to bone strength. A number of studies have included nutritional supplements along with resistance exercise, usually calcium and vitamin D, although most are not designed to assess their effect separate from exercise. Effect sizes for trials with and without nutritional supplements do not appear to differ systematically.43 Certainly, adequate nutritional status, including adequate mineral intake, is paramount for an optimal response to mechanical stimuli. However, whether intake above recommended levels potentiates exercise effects remains uncertain10 because in exercise studies, it is common to supplement volunteers in an attempt to eliminate calcium intake as a confounder rather than elucidate dose response. Long-Term Benefits

4.57 In a study of older postmenopausal women, Dalsky et al69 reported continued improvement in lumbar spine BMD after 22 months of combined resistance and weight-bearing training, although the major change was observed after 9 months of training. Similarly, in premenopausal women, Lohman et al35 reported significant increases in regional BMD after 5 to 12 months of training that were maintained at 18 months. Thus, the few available long-term studies in adults suggest that the main adaptation occurs early, and with further training, increases in BMD are maintained or slightly increased. A limitation of these studies has been the use of 2-dimensional imaging techniques (eg, dual-energy X-ray absorptiometry [DXA]), which cannot detect potentially important changes in bone geometry that may improve bone strength. In contrast, studies of detraining clearly show that the positive effects of exercise on BMD and BMC in premenopausal36,70 and postmenopausal women69 are rapidly reversed when regular exercise is stopped. Dose Response

Few studies have followed participants more than a few months to a year, and thus the bone response to long-term resistance exercise is unclear. In one of the longest running trials, postmenopausal women in the BEST study who continued to perform resistance exercise for 4 years continued to benefit.57 These women were encouraged to complete 2 sets of 6 to 8 repetitions at 70% to 80% of their 1 RM, 3 times per week. Four-year compliance with exercise averaged about 50% (±27%). In women who used HRT, trochanter BMD increased 1.5%, and femoral neck and lumbar spine BMD increased 1.2% for each standard deviation of percent exercise frequency (29.5%, the equivalent of about 1 day per week). HRT nonusers gained less BMD than users, although at the lumbar spine, the effect was similar and significant in both groups. The results of this study support observations of sitespecific results, as a significant increase in trochanter BMD was found after 1 year of exercise,52 whereas change in lumbar spine BMD was not significant until year

The optimal amount of resistance exercise to stimulate bone formation and how much is too much is not well described. In a review of the dose-response relationship between physical loading and bone characteristics, Smith and Gilligan71 concluded that increased cellular activity found in cell and organ culture research presented the likelihood of proportional reactions of bone to loading. Animal studies suggest a positive, linear relationship between loading and bone formation after a strain threshold is reached. Although the results of animal studies provide the rationale for the design of resistance exercise programs for bone loading, human studies are typically not designed to test directly the dose-response relationships between exercise and bone mass or strength. As noted, high-intensity, low-repetition resistance exercise generally is more effective than low-intensity, high-repetition resistance exercise.38 In one study, the increase in BMD was linearly related to the total amount of weight lifted over a 1-year resistance training program56; although

suggestive, the retrospective analysis was based on levels of program compliance and thus was not a direct test of dose response. Large-scale exercise trials are challenging. Consequently, most studies of resistance exercise have studied traditional weight-lifting regimens (eg, 2-3 sets, 8-12 repetitions, at a given intensity) against a control group rather than randomizing participants to various “doses.” Prospective studies designed specifically to address dose response are sorely needed. Fracture Risk The effects of resistance exercise on fracture risk may never be known, given the challenges of conducting an exercise trial of sufficient duration and sample size to analyze effects on fracture. Nevertheless, resistance training has been shown to have benefit for 2 important strategies for reducing fracture risk (ie, increasing BMD in young adults and achieving the highest possible peak bone mass and maintaining or increasing bone mass in middle-aged and older adults). The potential for lasting positive adaptations in bone geometry is just beginning to be explored but could prove to be a significant and possibly more important contributor to improved bone strength than potentially transient changes in BMD. Nevertheless, maintenance of BMD or small increases is important when viewed in light of the typical bone loss that occurs with menopause and aging. Even small increases in BMD, on the order of 3% to 5%, if maintained, can have an important effect on fracture risk, reducing risk by 20% to 40%.72 Moreover, with bisphonates and intermittent parathyroid hormone (PTH), small changes in BMD resulted in a higher than expected protective effect against fractures,73 and possibly small improvement in bone from mechanical strain may produce a similar effect. Given these other benefits, resistance exercise has other benefits that likely reduce fracture risk, including increasing muscle strength, increased or at least maintained muscle mass, and improved balance and agility in elderly individuals, and it is likely the benefits of

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resistance training for osteoporosis prevention and lowering fracture risk are underestimated with the focus only on BMD. Summary and Recommendations Development of osteoporosis is often attributed to either inadequate accumulation of peak bone mass prior to attainment of skeletal maturity or to excessive rate of bone loss during aging. Bone clearly responds to mechanical stress. Thus, there has been great interest in whether physical activity can stimulate greater bone mineral accretion or slow or reverse mineral loss once involution has begun. The bone response to strain has been well described in animal studies. Extrapolation to bone exercise programs suggests that effective programs must be dynamic, not static; exceed a threshold intensity; exceed a threshold frequency; be brief and intermittent; and impose an unusual loading pattern on the bones. Resistance exercise, which promotes lean mass and increases muscle strength, meets many of these criteria and may be especially beneficial for bone strength. This proposition has been reasonably well tested in women, with prospective studies demonstrating small but potentially important increases in regional BMD or at least slowed losses. Currently, our understanding of how to use resistance exercise for osteoporosis prevention is incomplete. Few studies have been done in children and men. Similarly, very few studies have been designed to test dose response. Nonmechanical factors (eg, nutrition, endocrine, and body composition, including initial bone density) undoubtedly interact with exercise and modify the bone response. Studies of exercise in combination with other factors are difficult, given the challenges of recruitment and retention of adequate numbers of participants and encouraging compliance with the interventions; thus, cotreatment studies are sorely needed. Despite the limitations, numerous studies have shown that resistance exercise is safe and that it promotes functional adaptations that promote bone health as well as eliciting other adaptations (eg, retention of muscle mass and improved

strength, agility, and balance) that protect against falls and fractures. High loads may be particularly beneficial, and thus it is important to encourage resistance training before significant bone loss to ensure that high-intensity exercise can be performed safely. A more conservative approach is warranted in the elderly and other persons with significant bone loss until the question of how much exercise is enough and how much is too much for skeletal health at different ages is answered. At any age, as much daily physical activity as the person can safely tolerate is recommended. Resistance training is preferable to weight bearing because the loads are multidirectional and are novel compared with typical daily weight-bearing activity (eg, walking). Although impact loading may be beneficial, especially in young persons, resistive exercise is safer for older persons and for clinical populations who already have bone loss. Higher intensity resistance exercise (eg, >70% of the 1 RM) that results in muscle strengthening is preferable to lower intensities and is generally safe because the load is relative to individual capacity. Nevertheless, some exercises (eg, squats, curl-ups) are contraindicated in persons with low bone mass. In middle-aged and older persons, especially postmenopausal women and patients treated with medications that may cause bone loss, screening for bone loss with DXA or comparable technology is recommended for an informed exercise prescription. Resistance exercise targeting major muscle groups is recommended 2 to 3 days per week at ~70% to 80% of 1 RM, 2 to 3 sets, and 6 to 8 repetitions per set. Novices should begin with lighter loads, adding weight in small increments until desired loads are achieved. Proper posture and lifting technique are crucial concerns, and practicing exercises with a physical therapist is desirable, as he or she can also recommend modifications and assistive devices, in consideration of individual body structure and special challenges. Although resistance exercise is safe for the majority of individuals, it is always advisable to discuss a new exercise program with one’s physician before undertaking it. In the case of persons with low bone mass, medications along with exercise may

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