Bisphosphonate use and risk of atypical femur fractures

1. In this retrospective cohort study, the risk of an atypical fracture increased with longer duration of bisphosphonate use while discontinuation led to a swift decrease in risk.

2. Asian patients, when compared to white patients, were at a higher risk of an atypical fracture.

Evidence Rating Level: 2 (Good)

Study Rundown: Bisphosphonates are one of the first-line therapies for osteoporosis treatment. This retrospective cohort study analyzed members of the Kaiser Permanente Southern California health care system who received bisphosphonate treatment for osteoporosis. The risk of atypical femur fractures increased with longer duration of therapy, Asian ethnicity, increased height, weight and greater than 1 year of glucocorticoid use. Discontinuation led to a decrease in the risk of atypical fracture. In a risk-benefit analysis, the number of fractures prevented outweighed the number of atypical fractures with more of a benefit in white patients compared to Asian patients.

This study had several limitations. Of note, alendronate was the the most common treatment exposure so these results cannot be generalized to other medications such as for instance, denusomab. Also, because the assessment of covariates was limited to the time period of Kaiser Permanente membership, it is possible that results of this study underestimated cumulative bisphosphonate exposure in those who had shorter membership. However, this was a large study capturing diverse demographics in a relevant population which suggests that its results may be generalizable to many patients. Overall, this study highlighted that constant reassessment of bisphosphonate use is important to avoid atypical fractures such as considerations for drug holidays. In addition, this study suggested that patients of Asian descent that have borderline bone mineral density scans or lack of high-risk factors should have careful consideration before initiation of bisphosphonates.

Click here to read the study in the NEJM

Relevant Reading: Atypical Femur Fractures: Review of Epidemiology, Relationship to Bisphosphonates, Prevention, and Clinical Management

In-Depth [retrospective cohort]: This was a retrospective cohort study of women greater than 50 years of age who received bisphosphonate therapy for osteoporosis enrolled in the Kaiser Permanente Southern California health care system from 2007 to 2017, covering a population of 196,129 women. After multivariable adjustment, atypical fracture risk with bisphosphonate use of 3-5 years was 8.86 (95% CI 2.79 to 28.20) and 8 years or more was 43.51 (95% CI 13.70 to 138.15) when compared to less 3 months. Other risk factors included Asian descent compared to Caucasian descent (HR 4.84, 95% CI 3.57 to 6.56), greater height (HR 1.28, 95% CI 1.15 to 1.43 for each 5 cm increment), greater weight (HR 1.15, 95% CI 1.11 to 1.19) and ≥1 year of glucocorticoid use (HR 2.28, 95% CI 1.52-3.43). In the 3-15 months after discontinuation, atypical fracture risk was reduced by 48% compared to less than 3 months after discontinuation. At 3 years, 149 hip fractures would be prevented with bisphosphonate use compared to 2 atypical fractures in Whites, while for Asians, there would be 91 prevented fractures with 8 atypical fractures. In summary, the risk of atypical fracture increased with duration of use and certain populations such as Asians and patients who may require long term steroid treatment should be counselled on the increased risk of atypical fractures.

Image: PD

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