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Boning Up on Bo..

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Bisphosphonates are the most commonly prescribed pharmacotherapy for the prevention and treatment of osteoporosis and are considered to have a relatively safe adverse effects profile. However, bisphosphonates have no safety data beyond ten years and recent evidence suggests that there may be an association between long-term bisphosphonate therapy and the risk of atypical femoral fractures.1-3 An atypical fracture is a subtrochanteric or femoral shaft fracture that occurs suddenly with minimal or no trauma; it may be preceded by weeks of thigh pain.1 Bisphosphonates inhibit hydroxyapatite crystals in the bone, resulting in the inhibition of bone turnover, which is responsible for the repair of microdamage that occurs in bone. Since bisphosphonates deposit in the bone with a half-life greater than 10 years, it is not unreasonable to consider the potential of causing oversuppression of bone turnover. Oversuppression of bone turnover would lead to the accumulation of microdamage on the bone. In fact, bisphosphonates have been shown to decrease bone surface mineralization by up to 92% after 3 years of therapy.4 This decrease in bone surface mineralization poses the possibility that bones could become brittle and unable to repair microdamage, potentially leading to an increased risk of atypical fractures. There are conflicting reports of the risk of atypical fractures with bisphosphonate use with many unanswered questions.1

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Meier et al. conducted a retrospective, case-controlled study to assess the association of bisphosphonate use and atypical femoral fracture. This single-center study included patients 50 years or older with a first subtrochanteric or femoral shaft fracture over a 2-year period. The fractures were classified as atypical or classic by radiographic review by two blinded physicians. A control group of 200 healthy individuals without femoral fracture was included. The patients were also evaluated for exposure to bisphosphonate therapy.1 Univariate and multivariate logistic regression and chi-square tests were utilized to analyze the difference between atypical fracture cases, classic fracture cases, and nonfracture controls.

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The investigators included 477 patients, 39 patients with an atypical fracture and 438 patients with a classic fracture. This resulted in an incidence rate for atypical fractures of 32 per million person-years compared to 357 classic fractures per million person-years. The study found a significant association of atypical fractures with bisphosphonate use. Of the atypical fracture patients, 82.1% had received bisphosphonate therapy compared with 6.4% of classic fracture patients (OR 66.9; 95% CI, 27.1-165.1) and 11.5% of nonfracture patients (OR 35.2; 95% CI, 13.9-88.8). The significant association remained after adjusting for potential risk factors. An association was also found between atypical femoral fracture risk and duration of bisphosphonate therapy.  When compared to no bisphosphonate use, the odd ratios for atypical fracture were 35.1 (95% CI, 10.0-123.6) for less than 2 years, 46.9 (95% CI, 14.2-154.4) for 2 to 5 years, 117.1 (95% CI, 34.2-401.7) for 5 to 9 years, and 175.6 (95% CI, 30.0-1027.6) for greater than 9 years of bisphosphonate therapy. Individuals with an atypical fracture had a higher risk (OR 42.6, 95% ...

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