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Denosumab vs. bisphosphonates in primary osteoporosis: a meta-analysis of comparative safety in randomized controlled trials

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Abstract

Denosumab and bisphosphonates for primary osteoporosis are generally well-tolerated, but their comparative safety remains unclear. We aimed to explore the comparative safety of denosumab and bisphosphonates in primary osteoporosis. Databases such as PubMed and Google Scholar were searched for relevant peer-reviewed randomized controlled trials published in English (as of December 2023). Trials comparing adverse events (AE) between denosumab and bisphosphonates in patients with primary osteoporosis were investigated. Data were pooled using a fixed- or random-effects model to determine the risk ratios (RR) and 95% confidence intervals (CIs) for various AEs in patients treated with denosumab in comparison to patients treated with bisphosphonates. Eleven trials (5,545 patients; follow-up period: 12–24 months) were included in this meta-analysis. All trials had a risk of bias (e.g., reporting bias linked to secondary endpoints and selection bias linked to random allocation). In comparison to bisphosphonates, denosumab was significantly associated with less withdrawal due to AEs (RR = 0.49; 95% CI 0.34–0.71), more five-point major adverse cardiovascular events (RR = 2.05; 95% CI 1.03–4.09), more cardiovascular AEs (RR = 1.61; 95% CI 1.07–2.41), more infections (RR = 1.14; 95% CI 1.02–1.27), more upper respiratory tract infections (RR = 1.56; 95% CI 1.08–2.25), less vertebral fractures (RR = 0.54; 95% CI 0.31–0.93), and less abdominal pain (RR = 0.44;95% CI 0.22–0.87). We explored the comparative safety of denosumab and bisphosphonates for primary osteoporosis, some of which could be attributed to their beneficial effects. However, all trials had a risk of bias. Further investigations are required to confirm our results.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Taku City Hospital, Saga, Japan

    Takaomi Kobayashi, Koji Ito & Takafumi Shimazaki

  2. Department of Orthopaedic Surgery, Faculty of Medicine, Saga University, Saga, Japan

    Takaomi Kobayashi, Tadatsugu Morimoto, Koji Ito, Masaaki Mawatari & Takafumi Shimazaki

  3. Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan

    Takaomi Kobayashi

  4. Department of Clinical Research, Amagi Chuo Hospital, Fukuoka, Japan

    Takaomi Kobayashi

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Takaomi Kobayashi, Tadatsugu Morimoto, Koji Ito, Masaaki Mawatari, and Takafumi Shimazaki were accountable and responsible for the conception and design of the study, acquisition of data, analysis, and interpretation of data, drafting the article or revising it critically for important intellectual content, and final approval of the version to be submitted.

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Kobayashi, T., Morimoto, T., Ito, K. et al. Denosumab vs. bisphosphonates in primary osteoporosis: a meta-analysis of comparative safety in randomized controlled trials. Osteoporos Int (2024). https://doi.org/10.1007/s00198-024-07118-0

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