Beyond Bone Remodeling: Denosumab’s Multisystemic Benefits in Musculoskeletal Health, Metabolism, and Age-Related Diseases—A Narrative Review
<b>Background:</b> Denosumab, a receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitor, demonstrates therapeutic effects beyond traditional osteoporosis management through the RANK/RANKL/osteoprotegerin pathway. <b>Methods:</b> This narrative review analyzed 37...
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MDPI AG
2025-03-01
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| Online Access: | https://www.mdpi.com/2227-9059/13/3/732 |
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| author | Yi-Ting Hung Wen-Tien Wu Ru-Ping Lee Ting-Kuo Yao Kuang-Ting Yeh |
| author_facet | Yi-Ting Hung Wen-Tien Wu Ru-Ping Lee Ting-Kuo Yao Kuang-Ting Yeh |
| author_sort | Yi-Ting Hung |
| collection | DOAJ |
| description | <b>Background:</b> Denosumab, a receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitor, demonstrates therapeutic effects beyond traditional osteoporosis management through the RANK/RANKL/osteoprotegerin pathway. <b>Methods:</b> This narrative review analyzed 37 studies (2018–2024) examining denosumab’s broader physiological effects and clinical applications. <b>Results:</b> Long-term safety data spanning 10 years showed sustained fracture prevention efficacy with a favorable benefit/risk profile. Compared to bisphosphonates, denosumab demonstrated superior outcomes in bone mineral density improvement and fracture risk reduction, particularly in elderly and frail populations. It enhanced muscular function by improving appendicular lean mass and grip strength while reducing fall risk. The drug showed potential cardiovascular benefits through its effects on cardiac and smooth muscle function. Notably, denosumab use was associated with reduced Type II diabetes mellitus risk through improved glucose metabolism. Additionally, it demonstrated promise in osteoarthritis treatment by suppressing osteoclast activity and chondrocyte apoptosis. While there are multisystem benefits, vigilance is required regarding adverse events, including hypocalcemia, infection risk, cutaneous reactions, and osteonecrosis of the jaw. <b>Conclusions:</b> Denosumab exhibits potential benefits in bone and systemic metabolism. Further research is needed to fully understand its therapeutic potential beyond osteoporosis and optimize clinical applications across different populations. |
| format | Article |
| id | doaj-art-08d03e96d9644eb4b23eb512bf32ba87 |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-08d03e96d9644eb4b23eb512bf32ba872025-08-20T03:43:34ZengMDPI AGBiomedicines2227-90592025-03-0113373210.3390/biomedicines13030732Beyond Bone Remodeling: Denosumab’s Multisystemic Benefits in Musculoskeletal Health, Metabolism, and Age-Related Diseases—A Narrative ReviewYi-Ting Hung0Wen-Tien Wu1Ru-Ping Lee2Ting-Kuo Yao3Kuang-Ting Yeh4School of Medicine, Tzu Chi University, Hualien 970374, TaiwanSchool of Medicine, Tzu Chi University, Hualien 970374, TaiwanInstitute of Medical Sciences, Tzu Chi University, Hualien 970374, TaiwanDepartment of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, TaiwanSchool of Medicine, Tzu Chi University, Hualien 970374, Taiwan<b>Background:</b> Denosumab, a receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitor, demonstrates therapeutic effects beyond traditional osteoporosis management through the RANK/RANKL/osteoprotegerin pathway. <b>Methods:</b> This narrative review analyzed 37 studies (2018–2024) examining denosumab’s broader physiological effects and clinical applications. <b>Results:</b> Long-term safety data spanning 10 years showed sustained fracture prevention efficacy with a favorable benefit/risk profile. Compared to bisphosphonates, denosumab demonstrated superior outcomes in bone mineral density improvement and fracture risk reduction, particularly in elderly and frail populations. It enhanced muscular function by improving appendicular lean mass and grip strength while reducing fall risk. The drug showed potential cardiovascular benefits through its effects on cardiac and smooth muscle function. Notably, denosumab use was associated with reduced Type II diabetes mellitus risk through improved glucose metabolism. Additionally, it demonstrated promise in osteoarthritis treatment by suppressing osteoclast activity and chondrocyte apoptosis. While there are multisystem benefits, vigilance is required regarding adverse events, including hypocalcemia, infection risk, cutaneous reactions, and osteonecrosis of the jaw. <b>Conclusions:</b> Denosumab exhibits potential benefits in bone and systemic metabolism. Further research is needed to fully understand its therapeutic potential beyond osteoporosis and optimize clinical applications across different populations.https://www.mdpi.com/2227-9059/13/3/732osteoporosissarcopeniaosteosarcopenia denosumabRANKL inhibitorRANK/RANKL/OPG pathway (RRO pathway) |
| spellingShingle | Yi-Ting Hung Wen-Tien Wu Ru-Ping Lee Ting-Kuo Yao Kuang-Ting Yeh Beyond Bone Remodeling: Denosumab’s Multisystemic Benefits in Musculoskeletal Health, Metabolism, and Age-Related Diseases—A Narrative Review Biomedicines osteoporosis sarcopenia osteosarcopenia denosumab RANKL inhibitor RANK/RANKL/OPG pathway (RRO pathway) |
| title | Beyond Bone Remodeling: Denosumab’s Multisystemic Benefits in Musculoskeletal Health, Metabolism, and Age-Related Diseases—A Narrative Review |
| title_full | Beyond Bone Remodeling: Denosumab’s Multisystemic Benefits in Musculoskeletal Health, Metabolism, and Age-Related Diseases—A Narrative Review |
| title_fullStr | Beyond Bone Remodeling: Denosumab’s Multisystemic Benefits in Musculoskeletal Health, Metabolism, and Age-Related Diseases—A Narrative Review |
| title_full_unstemmed | Beyond Bone Remodeling: Denosumab’s Multisystemic Benefits in Musculoskeletal Health, Metabolism, and Age-Related Diseases—A Narrative Review |
| title_short | Beyond Bone Remodeling: Denosumab’s Multisystemic Benefits in Musculoskeletal Health, Metabolism, and Age-Related Diseases—A Narrative Review |
| title_sort | beyond bone remodeling denosumab s multisystemic benefits in musculoskeletal health metabolism and age related diseases a narrative review |
| topic | osteoporosis sarcopenia osteosarcopenia denosumab RANKL inhibitor RANK/RANKL/OPG pathway (RRO pathway) |
| url | https://www.mdpi.com/2227-9059/13/3/732 |
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