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Risk of Cataract Surgery and Age-Related Macular Degeneration After Initiation of Denosumab vs Zoledronic Acid for Osteoporosis: A Multi-Database Cohort Study

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Abstract

Background and Objective

There is a relative lack of head-to-head comparisons of denosumab against other osteoporosis drugs on safety. We aimed to explore ocular outcomes in patients with osteoporosis initiating denosumab vs zoledronic acid.

Methods

We conducted a cohort study using claims data (2010–15) from two large US commercial insurance databases including patients with osteoporosis who were aged 50 years or older and initiators of denosumab or zoledronic acid. The primary outcomes were (1) receipt of cataract surgery and development of (2) wet age-related macular degeneration and (3) dry age-related macular degeneration within 365 days after initiation of denosumab vs zoledronic acid. Propensity score fine stratification and weighting were used to control for potential confounding, and we calculated the incidence rate and hazard ratio for each outcome in the cohorts. The estimates from the two databases were combined with a fixed-effects model meta-analysis.

Results

The study cohort included 50,821 denosumab and 67,471 zoledronic acid initiators. In the propensity score-weighted analysis, compared to zoledronic acid use, denosumab was associated with a modestly decreased risk of undergoing cataract surgery (hazard ratio 0.91; 95% confidence interval 0.85–0.98) but not with the risk of wet age-related macular degeneration (hazard ratio 1.29; 95% confidence interval 0.99–1.70) or dry age-related macular degeneration (hazard ratio 1.03; 95% confidence interval 0.98–1.09).

Conclusions

In this large population-based cohort study of 118,292 patients with osteoporosis, initiation of denosumab was associated with a modestly decreased risk of cataract surgery vs zoledronic acid. The risk of age-related macular degeneration was similar between the two drugs.

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Author notes

  1. Hemin Lee and Yinzhu Jin should be regarded as joint first authors.

Authors and Affiliations

  1. Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3-030, Boston, MA, 02120, USA

    Hemin Lee, Yinzhu Jin, Theodore N. Tsacogianis & Seoyoung C. Kim

  2. Beetham Eye Institute, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA

    Miin Roh

  3. Graduate School of Urban Public Health, University of Seoul, Seoul, Republic of Korea

    Sangshin Park

  4. Department of Health Convergence, Ewha Women’s University, Seoul, Republic of Korea

    Nam-Kyong Choi

  5. Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Seoyoung C. Kim

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  1. Hemin Lee
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Contributions

Hemin Lee verified the analytical methods and drafted the manuscript. Yinzhu Jin conducted the statistical analysis and drafted the manuscript. Miin Roh contributed to the study conception and reviewed the manuscript for important intellectual content. Theodore N. Tsacogianis conducted the statistical analysis. Sangshin Park verified the analytical methods and reviewed the manuscript for important intellectual content. Nam-Kyong Choi contributed to the study conception, verified the analytical methods, and reviewed the manuscript for important intellectual content. Seoyoung C. Kim supervised the project, contributed to the study conception, verified the analytical methods, and reviewed the manuscript for important intellectual content.

Corresponding author

Correspondence to Seoyoung C. Kim.

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Funding

This study was supported by the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital.

Conflict of interest

Seoyoung C. Kim has received research grants to the Brigham and Women’s Hospital from Pfizer, Roche, and Bristol-Myers Squibb for unrelated topics. Hemin Lee, Yinzhu Jin, Miin Roh, Theodore N. Tsacogianis, Sangshin Park, and Nam-Kyong Choi have no conflicts of interest that are directly relevant to the content of this article.

Ethics approval

Personal identifiers were removed from the dataset before the analysis to protect subject confidentiality. Therefore, patient informed consent was not required. The study protocol was approved by the Institutional Review Board of Brigham and Women’s Hospital.

Consent to participate

Not applicable.

Prior posting and presentation

This work is the sole product of the authors and has been presented at the 2018 International Conference on Pharmacoepidemiology and Therapeutic Risk Management.

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Lee, H., Jin, Y., Roh, M. et al. Risk of Cataract Surgery and Age-Related Macular Degeneration After Initiation of Denosumab vs Zoledronic Acid for Osteoporosis: A Multi-Database Cohort Study. Drugs Aging 37, 311–320 (2020). https://doi.org/10.1007/s40266-020-00745-2

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  • DOI: https://doi.org/10.1007/s40266-020-00745-2

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