Endocrinol Metab.  2025 Feb;40(1):47-56. 10.3803/EnM.2024.2125.

Long-Term Efficacy and Safety of Denosumab: Insights beyond 10 Years of Use

• Ha J
• Lee YJ
• Kim J
• Jeong C
• Lim Y
• Lee J
• Baek KH
• on Behalf of the Catholic Medical Center Bone Research Group

• KMID: 2565250
• DOI: http://doi.org/10.3803/EnM.2024.2125

Abstract

Osteoporosis management in post-menopausal women focuses on fracture prevention, with denosumab as a key therapeutic option. Despite its proven efficacy in reducing fracture risk and increasing bone mineral density (BMD) over 10 years, its long-term impact remains uncertain. We evaluated the literature on its efficacy and safety beyond the initial decade. Clinical trials and real-world studies confirm denosumab’s sustained efficacy, especially in lumbar spine BMD, with hip BMD stabilizing. Concerns about adverse events (AEs) like hypocalcemia and osteonecrosis of the jaw necessitate vigilant monitoring. Risks of atypical femoral fractures and malignancies also require attention, despite unclear links to treatment duration. Clinical guidelines for denosumab beyond 10 years are limited, emphasizing the need for careful monitoring. In certain scenarios, such as advanced chronic kidney disease, prolonged denosumab may be required to balance AE risks with fracture prevention benefits. Denosumab shows potential for long-term efficacy in augmenting BMD; however, monitoring for AEs is crucial to guide clinical decision-making effectively.

Keyword

Osteoporosis; Denosumab; Bone density; Drug safety; Long-term care

Figure

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  Fig. 1. Prediction of the duration of denosumab treatment and percentage change from baseline in lumbar spine bone mineral density. Adapted from Lee et al. [27]. FREEDOM, Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months.

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  Fig. 2. Prediction of the duration of denosumab treatment and percentage change from baseline in total hip bone mineral density. Adapted from Lee et al. [27]. FREEDOM, Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months.

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