Comparative effectiveness of denosumab, teriparatide, and zoledronic acid among frail older adults: a retrospective cohort study

• Published in: Osteoporosis international Vol. 32; no. 3; pp. 565 - 573
• Main Authors: Zullo, A. R., Lee, Y., Lary, C., Daiello, L. A., Kiel, D. P., Berry, S. D.
• Format: Journal Article
• Language: English
• Published: London Springer London 01-03-2021; Springer Nature B.V
• Subjects: Acids; Aged; Aged, 80 and over; Bone Density Conservation Agents - therapeutic use; Cohort analysis; Cohort Studies; Denosumab - therapeutic use; Endocrinology; Female; Fractures; Frail Elderly; Hip; Humans; Immunotherapy; Male; Medicare; Medicine; Medicine & Public Health; Monoclonal antibodies; Nursing homes; Older people; Oral administration; Original Article; Orthopedics; Osteoporosis; Osteoporosis - drug therapy; Parathyroid hormone; Regression analysis; Retrospective Studies; Rheumatology; Teriparatide - therapeutic use; United States; Zoledronic acid; Zoledronic Acid - therapeutic use; United States; United States > US; Comparative effectiveness research; Zoledronic acid; Nursing homes; Hip fractures; Denosumab; Teriparatide
• ISSN: 0937-941X; 1433-2965
• DOI: 10.1007/s00198-020-05732-2

Summary
The comparative effects of zoledronic acid, denosumab, and teriparatide for preventing hip fractures in frail older adults, especially those in nursing homes, were unknown. We found that denosumab and zoledronic acid may be as effective as teriparatide for hip fracture prevention in nursing home residents.
Introduction
Several non-oral drugs exist for osteoporosis treatment, including zoledronic acid (ZA), denosumab, and teriparatide. Little data exist on the comparative effectiveness of these drugs for hip fracture prevention in frail older adults. We examined their comparative effectiveness in one of the frailest segments of the US population—nursing home (NH) residents.
Methods
We conducted a national retrospective cohort study of NH residents aged ≥ 65 years using 2012 to 2016 national US Minimum Data Set clinical assessment data and linked Medicare claims. New parenteral ZA, denosumab, and teriparatide use was assessed via Medicare Parts B and D; hip fracture outcomes via Part A; and 125 covariates for confounding adjustment via several datasets. We used inverse probability weighted (IPW) competing risk regression models to compare hip fracture risk between groups with teriparatide as the reference.
Results
The study cohort (
N
 = 2019) included 1046 denosumab, 578 teriparatide, and 395 ZA initiators. Mean age was 85 years, 90% were female, and 68% had at least moderate functional impairment. Seventy-two residents (3.6%) had a hip fracture and 1100 (54.5%) died over a mean follow-up of 1.5 years. Compared to teriparatide use, denosumab use was associated with a 46% lower risk of hip fracture (HR 0.54, 95% CI 0.29–1.00) and no difference was observed for ZA (HR 0.70, 95% CI 0.26–1.85).
Conclusions
Denosumab and ZA may be as effective as teriparatide for hip fracture prevention in frail older adults. Given their lower cost and easier administration, denosumab and ZA are likely preferable non-oral treatments for most frail, older adults.