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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Main Authors: Yi-Ting Hung, Wen-Tien Wu, Ru-Ping Lee, Ting-Kuo Yao, Kuang-Ting Yeh
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Biomedicines
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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.
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institution Kabale University
issn 2227-9059
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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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