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Comparative Study
. 2019 Apr 5;2(4):e192416.
doi: 10.1001/jamanetworkopen.2019.2416.

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

Alma B Pedersen  1 , Uffe Heide-Jørgensen  1 , Henrik T Sørensen  1 , Daniel Prieto-Alhambra  2   3 , Vera Ehrenstein  1
Affiliations
Comparative Study

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

Alma B Pedersen et al. JAMA Netw Open. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: The Department of Clinical Epidemiology at Aarhus University Hospital is involved in studies with funding from various pharmaceutical companies as institutional research grants. One such study, specifically an ongoing regulator-mandated postauthorization safety study of denosumab among women with postmenopausal osteoporosis, funded by Amgen Inc through institutional funding to Aarhus University, is related to and has overlapping populations with the present study. Drs Heide-Jørgensen, Sørensen, and Ehrenstein have been involved in that postauthorization safety study as institutional employees. Dr Sørensen reported grants from Amgen Inc during the conduct of the study. Dr Prieto-Alhambra reported receiving grants and speaker fees from Amgen, the market authorization holder for denosumab, and receiving grants, speaker fees, and consulting fees from UCB Biopharma, paid to the University of Oxford, outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Crude and Weighted Cumulative Incidences of Hip Fracture and Any Fracture Following Initiation of Denosumab and Alendronate
See this image and copyright information in PMC

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