Bisphosphonates and Fractures of the Subtrochanteric or Diaphyseal Femur

• Published in: The New England journal of medicine Vol. 362; no. 19; pp. 1761 - 1771
• Main Authors: Black, Dennis M, Kelly, Michael P, Genant, Harry K, Palermo, Lisa, Eastell, Richard, Bucci-Rechtweg, Christina, Cauley, Jane, Leung, Ping Chung, Boonen, Steven, Santora, Arthur, de Papp, Anne, Bauer, Douglas C
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 13-05-2010
• Subjects: Alendronate - adverse effects; Biological and medical sciences; Bone density; Bone Density Conservation Agents - adverse effects; Bone Density Conservation Agents - therapeutic use; Confidence Intervals; Diphosphonates - adverse effects; Diphosphonates - therapeutic use; Female; Femoral Fractures - chemically induced; Femoral Fractures - epidemiology; Femoral Fractures - prevention & control; Fractures; General aspects; Hip Fractures - chemically induced; Hip Fractures - epidemiology; Humans; Imidazoles - adverse effects; Medical sciences; Older people; Osteoporosis; Osteoporosis - drug therapy; Randomized Controlled Trials as Topic; Women; Medicine; Femur; Antiosteoporotic; Antiosteoclastic agent; Diseases of the osteoarticular system; Fracture; Trauma; Bisphosphonates; Diaphysis
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1001086

Recent case reports and series have identified a subgroup of atypical femoral-shaft fractures associated with bisphosphonate use. This study analyzed data from three large, randomized bisphosphonate trials. Subtrochanteric or diaphyseal femur fractures were very rare, even among women who had been treated with bisphosphonates for as long as 10 years. In patients with osteoporosis, proven benefits for fracture reduction appear to outweigh the possible risk of femoral-shaft fractures.
This study analyzed data from three large, randomized bisphosphonate trials. Subtrochanteric or diaphyseal femur fractures were very rare, even among women who had been treated with bisphosphonates for as long as 10 years.
Several case series have described cases of “atypical” subtrochanteric and diaphyseal fractures of the femoral shaft and have suggested that the risk may be increased in long-term users of bisphosphonates.
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Descriptions of associated atypical characteristics vary but have been described as a simple transverse or oblique (<30 degrees) fracture with cortical beaking and diffuse cortical thickening.
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Clinical associations that have been mentioned in some reports include low-level trauma, prodromal pain or evidence of a previous stress fracture, contralateral changes, and the use of specific concomitant drugs (including corticosteroids),
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antiresorptive drugs (including hormone-replacement therapy),
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and proton-pump inhibitors.
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However, these . . .