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

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Abstract

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.

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Funding

This study was supported by grants R01AG045441, RF1AG061221, R01AG065722, and R21AG061632 from the National Institute on Aging (NIA) and by grant U54GM1156775 from the National Institute of General Medical Sciences (NIGMS), which funds Dr. Zullo and Advance Clinical and Translational Research (Advance-CTR). Dr. Zullo is also supported by a Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship in Health Services Research and Development. Dr. Lary is supported, in part, by grant P20GM121301 from NIGMS (PI Lucy Liaw).

Author information

Authors and Affiliations

  1. Department of Health Services, Policy, and Practice, Brown University School of Public Health, 121 South Main Street, Box G-S121-8, Providence, RI, 02912, USA

    A. R. Zullo, Y. Lee & L. A. Daiello

  2. Center of Innovation in Long-Term Services and Supports, Providence Veterans Affairs Medical Center, Providence, RI, USA

    A. R. Zullo

  3. Department of Pharmacy, Lifespan—Rhode Island Hospital, Providence, RI, USA

    A. R. Zullo

  4. Department of Epidemiology, Brown University School of Public Health, 121 South Main Street, Box G-S121-8, Providence, RI, USA

    A. R. Zullo

  5. Center for Outcomes Research, Maine Medical Center, Portland, ME, USA

    C. Lary

  6. Alzheimer’s Disease and Memory Disorders Center, Rhode Island Hospital, RI, Providence, USA

    L. A. Daiello

  7. Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA

    D. P. Kiel & S. D. Berry

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  1. A. R. Zullo
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  2. Y. Lee
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  6. S. D. Berry
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Corresponding author

Correspondence to A. R. Zullo.

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Conflicts of interest

Dr. Berry previously received grant money from Amgen unrelated to the current project. Dr. Kiel previously received grant support from Merck Sharp & Dohme and Amgen for clinical trials of osteoporosis treatments and grant funding for investigator initiated research from Amgen and Radius Health unrelated to the current project. All other authors have no relevant conflicts of interest to report.

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The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Zullo, A.R., Lee, Y., Lary, C. et al. Comparative effectiveness of denosumab, teriparatide, and zoledronic acid among frail older adults: a retrospective cohort study. Osteoporos Int 32, 565–573 (2021). https://doi.org/10.1007/s00198-020-05732-2

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  • DOI: https://doi.org/10.1007/s00198-020-05732-2

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