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High fracture risk: How to define, how to treat? Dr Emmanuel BIVER Department of Bone Diseases Geneva University Hospitals and Faculty of ...
High fracture risk: How to define, how to treat? Dr Emmanuel BIVER Department of Bone Diseases Geneva University Hospitals and Faculty of Medicine 8. Basler Fortbildung in praktischer Osteologie, Universitätsspital Basel, 26. Januar 2017
What is a high fracture risk?
Age BMD 7%
-2.5SD Need to take account of the BMD and its interaction with age
Kanis et al. Osteoporos Int 2001 Lippuner et al. Osteoporos Int 2009
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What is a high fracture risk?
Fracture site
Sambrook et al. Lancet 2006
Kanis et al. Osteoporos Int 2001
What is a high fracture risk?
Clinical risk factors
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Schweizerische Vereinigung gegen die Osteoporose: Empfehlungen 2015 Postmenopausale Frauen und Männer ab 60. Lebensjahr Allgemeine Risikofaktoren Wirbelfraktur(en) Nichtvertebrale Fraktur(en) nach dem 50. Lebensjahr (Ausnahme: Finger, Zehen, Schädel, Knöchel) Proximale Femurfraktur eines Elternteils Untergewicht (BMI 4) Moderat (RR= 1.5-2) Moderat (RR= 1.5-2) Schwer (RR= 2-4) Schwer (RR= 2-4)
“All fracture locations apart from rib (men) and ankle (women) resulted in increased subsequent fracture risk”
Center, JAMA. 2007;297:387-394
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GIOP Vertebral fracture rate (*per 100 person-years, with 95 % confidence intervals) by study length of follow-up among GC initiators (50 with osteoporosis and no recent fracture (not yet fracture), falls, older age, poorer health status, comorbidities, and other potential fall risk factors were predictive of imminent risk for fracture. Bonafede et al, Arch Osteoporos 2016
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Treatment: Key messages Exclusion of secondary causes of osteoporosis or other causes of bone fragility before pharmacological intervention.
- Regular physical activity - Prevention of falls - Correction of nutritional deficiencies, including vitamin D repletion - Pharmacological intervention.
Pharmacological intervention: Evidence base Medicine Drug
Alendronate
Bisphosphonates
Effect on fracture risk reduction demonstrated in clinical trials Vertebral Non-vertebral Hip + + +
Risedronate
+
+
+
Ibandronate
+
Post hoc
−
Zoledronate
+
+
+
Raloxifene
+
Post hoc
−
SERMs
Swissmedic indication
- Osteoporosis treatment - Prevention and treatment of osteoporosis - Osteoporosis treatment (to reduce vertebral fractures) - Osteoporosis treatment - Prevention of fracture after a hip fracture - Prevention and treatment of GIOP - Prevention and treatment of osteoporosis (to reduce vertebral fractures)
Bazedoxifene
+
Post hoc
−
Anti-RANKL monoclonal antibodies
Denosumab
+
+
+
- Osteoporosis treatment (to reduce vertebral and non-vertebral fractures)
Parathyroid hormone
Teriparatide
+
+
−
- Osteoporosis and GIOP treatment with high risk of fracture.
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Potential use of teriparatide as first-line treatment option Teriparatide (FOSTEO): reimbursed as second-line treatment in postmenopausal women and men with increased fracture risk, specifically in patients with incident fractures under antiresorptive therapy or patients with glucocorticoid-induced osteoporosis and intolerance to antiresorptives.
Meier et al, Swiss Med Wkly. 2014;144:w13952
Sequential therapy with teriparatide and antiresorptive drugs • Teriparatide No treatment • Teriparatide Bisphosphonate • Teriparatide Denosumab • Bisphosphonate Teriparatide • Denosumab Teriparatide
x x
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Abaloparatide: analog of PTHrp that selectively binds to the parathyroid hormone type 1
→ more pronounced anabolic action on bone compared with teriparatide?
Miller, JAMA. 2016;316(7):722-733.
Romosozumab: a monoclonal antibody that binds and inhibits sclerostin, a negative regulator of bone formation
→ increases bone formation and decreases bone resorption.
McClung. N Engl J Med. 2014
Cosman. N Engl J Med. 2016
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Take Home messages: High risk of fracture • Age, BMD, clinical risk factors…, falls… • Some clinical situations at particularly high risk of fracture: recent vertebral or hip fractures • Tools: DXA, FRAX • Imminent risk of fracture • Treatment: fall prevention + bone fragility treatment
