Bisphosphonate Use Associated with Increased Fracture Risk

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Bisphosphonate use, especially for more than five years, is associated with an increased risk of atypical femoral fractures, but this risk falls considerably after discontinuation, according to a Nationwide Danish an analysis and review presented on September 13 at the American Society for Bone and Mineral Research (ASBMR) annual meeting which was held virtually.

One-third of atypical femoral fractures occur in individuals with no exposure to bisphosphonates, reported David Bauer, M.D., of the University of California, San Francisco.

“Concerns about atypical femoral fractures and bisphosphonates should not dissuade patients and providers from short term (three to five years) use of bisphosphonates,”Dr. Bauer said. “Drug holidays where bisphosphonates are stopped after three to five years of use should greatly reduce the risk of atypical femoral fractures and allow safe short-term use of bisphosphonates.”

Atypical femoral fractures occur infrequently, but they are a serious complication of anti-resorptive treatments. While it has been shown that prolonged bisphosphonate use is associated with higher atypical femoral fracture risk, there are few population-based studies with thorough long-term analysis of medication use and radiographic validation of atypical femoral fractures.

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In this study of data from the Danish National Healthcare system, which maintains longitudinal records of medication use, fracture events and comorbidities, researchers examined the prospective relationship between bisphosphonate use and atypical femoral fractures between 2010 to 2015 in 1.9 million people aged over 50 years. Digitized pre and post-operative radiographic images from adults with subtrochanteric and femoral shaft fractures (n=4973; 96 percent of all fractures at those locations in the country) were blindly reviewedto identify 2014 ASBMR major and minor criteria. The review identified 189 atypical femoral fractures and 65 individuals with atypical femoral fractures.

One year after bisphosphonate discontinuation, the risk of atypical femoral fracture fell dramatically (RH=0.29, CI: 0.09, 0.90). Atypical femoral fracture risk was increased among patients with rheumatoid arthritis or hypertension, but was unrelated to age, gender, diabetes or other medication use.

“Atypical femoral fractures are found among individual using bisphosphonates, but the number of atypical femoral fractures is very low compared to the number of fractures prevented by the use of bisphosphonates,” Dr. Bauer said. “We need to better understand why atypical femoral fractures occur in those without bisphosphonate use.”

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REFERENCE

[1061] Bisphosphonate Use and Risk of Atypical Femoral Fractures: A Nationwide Danish Analysis with Blinded Radiographic Review. Douglas Bauer. September 13. ASMBR 2020 Annual Meeting Virtual Event.