Comparison of Risk of Osteoporotic Fracture in Denosumab vs Alendronate Treatment Within 3 Years of Initiation.

Importance: Head-to-head randomized clinical trials showed greater efficacy of denosumab vs alendronate in improving bone mineral density. Although there is an association of changes in bone mineral density with reductions in fracture risk, the magnitude of the association is not well established. Objective: To compare the risk of hip and any fracture in patients treated with denosumab and alendronate in routine practice settings. Design, Setting, and Participants: This Danish nationwide, population-based, historical cohort study of a population with universal access to health care used prospectively collected, individually linked data from Danish health registries with complete follow-up. Cohorts consisted of 92 355 individuals 50 years or older who were new users of denosumab (n = 4624) or alendronate (n = 87 731) from May 2010 to December 2017 after at least 1 year without an antiosteoporosis medication dispensing. Exposures: Initiation of denosumab or alendronate. Main Outcomes and Measures: The primary outcome was hospitalization for hip fracture, and the secondary outcome was hospitalization for any fracture. Inverse probability of treatment weights and the intention-to-treat approach were used to calculate cumulative incidences and adjusted hazard ratios (aHRs) with 95% CIs. Results: Of the 92 355 included patients, 75 046 (81.3%) were women, and the mean (SD) age was 71 (10) years. The denosumab cohort had a lower proportion of men than the alendronate cohort (12.7% [589] vs 19.0% [16 700]), while age distributions were similar in the 2 cohorts. Within 3 years of follow-up, initiation of denosumab or alendronate was associated with cumulative incidences of 3.7% and 3.1%, respectively, for hip fracture and 9.0% and 9.0%, respectively, for any fracture. Overall, the aHRs for denosumab vs alendronate were 1.08 (95% CI, 0.92-1.28) for hip fracture and 0.92 (95% CI, 0.83-1.02) for any fracture. The aHR of denosumab vs alendronate for hip fracture was 1.07 (95% CI, 0.85-1.34) among patients with a history of any fracture and 1.05 (95% CI, 0.83-1.32) among patients without history of fracture. The aHR for any fracture for denosumab vs alendronate was 0.84 (95% CI, 0.71-0.98) among patients with a history of any fracture and 0.77 (95% CI, 0.64-0.93) among patients with no history of fracture. Conclusions and Relevance: Treatment with denosumab and alendronate was associated with similar risks of hip or any fracture over a 3-year period, regardless of fracture history.