Background/Purpose: Patients with rheumatoid arthritis (RA) are diagnosed with osteoporosis earlier than those without, and are therefore exposed to bisphosphonates for longer. However, the increasing use of bisphosphonates has raised concerns about atypical femur fracture. While patients with RA are at risk of atypical femur fracture, the impact of RA on the occurrence of atypical femur fracture is unclear. Here, we investigate the contribution of RA and other clinical factors on the development of bisphosphonates-related atypical femur fracture.

Methods: We conducted a retrospective case-control study in patients who have taken bisphosphonates for at least 1 year in Seoul St. Mary’s Hospital, between 2008 and 2015. We identified patients with atypical femur fracture by reviewing surgical and radiographic records. Atypical femur fracture was classified based on the 2013 American Society for Bone and Mineral Research task force criteria. Three age- and sex- matched controls without the history of atypical femur fracture were randomly selected to each patient with an atypical femur fracture. Cox proportional hazards models were used to analyze the independent contribution of risk factors for bisphosphonates-related atypical femur fracture occurrence.

Results: In 35,104 patients who were prescribed BPs for at least a year during 8 year period, 43 female patients (mean age, 68 years) suffered atypical femur fracture (0.12%). Patients with atypical femur fracture exposed to bisphosphonates for 7.3 years. Patients with atypical femur fracture had exposed to bisphosphonates longer and continued bisphosphonates treatment without cessation. Twenty-eight percent of patients with atypical femur fracture were comorbid with RA. Glucocorticoids and disease modifying anti-rheumatic drugs were frequently used in patients with atypical femur fracture. Multivariate Cox regression analyses estimated that the hazards ratio of atypical femur fracture increased by 9.2 for long-term glucocorticoids use at least one year, 7.2 for prolonged bisphosphonates exposure without cessation and 1.3 for every kg/m² of the increased body mass index (BMI).

Conclusion : The incidence of bisphosphonates-related atypical femur fracture is very low. Although there is an association between atypical femur fracture and long-term bisphosphonates use, clinicians should remember that bisphosphonates significantly reduce the risk of osteoporotic fracture. We suggested that long-term bisphosphonates use without cessation, prolonged glucocorticoids use and higher BMI are risk factors for atypical femur fracture. These patients should be carefully followed up with X-rays or dual-energy bone densitometry during bisphosphonates treatment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/bisphosphonates-related-atypical-femur-fractures-8-years-experience-in-a-single-center/