Douglas C Bauer 1 2, Dennis M Black 2, Rick Dell 3, Bo Fan 4, Christopher D Smith 5, Martin T Ernst 5, Anne G Jurik 6, Jens B Frøkjær 7, Mikael Boesen 8, Eric Vittinghoff 2, Bo Abrahamsen 5 9
J Clin Endocrinol Metab. 2024 Jan 10:dgae023.
doi: 10.1210/clinem/dgae023. Online ahead of print.
Abstract
Context: Prolonged bisphosphonate (BP) treatment for osteoporosis prevents hip and other fractures but causes atypical femoral fractures (AFF).
Objective: To establish the relationship between patterns of BP use and the risk of AFF and hip fractures. Other potential risk factors for AFF were also examined.
Design: Population-based case-cohort study.
Setting: The Danish National Healthcare system maintains longitudinal records of medication use, healthcare utilization, and x-ray images.
Participants: Among all 1.9 million Danish adults ≥50, those with subtrochanteric or femoral shaft fractures between 2010-2015 (n = 4,973) were identified and compared to a random sample (n = 37,021).
Predictors: Bisphosphonate use was collected from 1995-2015.
Main outcome measures: Fracture radiographs (n = 4,769) were reviewed by blinded study radiologists to identify AFFs (n = 181) using established criteria. Traditional hip fractures in the random sample (n = 691) were identified by ICD-10.
Results: Compared to <1 year of BP use, 5-7 years of use was associated with a 7-fold increase in AFF [adjusted HR = 7.29 (CI: 3.07,17.30)]; the risk of AFF fell quickly after discontinuation. The 5-year number-needed-to-harm for one AFF was 1,424, while the 5-year number-needed-to-treat to prevent one hip fracture was 56. Glucocorticoid and proton pump inhibitor use were independently associated with increased AFF risk. Thirty-one percent of those with AFF had no BP exposure.
Conclusions: The risk of AFF increases with duration of BP use but the beneficial effects of BP therapy in adults ≥50 dramatically exceed this increased risk. Nearly one-third of those with AFF have no BP exposure.