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已发表论文
地诺单抗治疗原发性骨质疏松症及其对中国人群肌肉减少症的影响：来自临床证据和 RANKL 通路孟德尔随机化的见解
Authors Li S , Hu S, Zheng X, Ku X, Zou J , Wang L, Nie G, Liu Y , Tian C , Ran J , Yang X, Yan M, Yin Y, Liu Y, Wan J, Peng W
Received 17 June 2025
Accepted for publication 7 November 2025
Published 15 November 2025 Volume 2025:20 Pages 2065—2077
DOI https://doi.org/10.2147/CIA.S547803
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Zhi-Ying Wu
Shaotian Li,1,* Shanshan Hu,2,* Xiaoli Zheng,2,* Xiong Ku,2,* Jingfeng Zou,1 Liping Wang,1 Guqiao Nie,1 Yiting Liu,1 Chunhui Tian,1 Jiajia Ran,1 Xin Yang,1 Mi Yan,1 Yilan Yin,1 Yun Liu,1 Jingjing Wan,1 Wen Peng1
1Union Hospital TongJi Medical College HuaZhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Geriatric hospital Affiliated to Wuhan University of science and technology, Wuhan, Hubei, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Wen Peng, Union Hospital TongJi Medical College HuaZhong University of Science and Technology, 1277 Jiefang Avenue, Jianghan District, Wuhan, Hubei, People’s Republic of China, Tel +86 13986074846, Email pengwen666@sina.com Jingjing Wan, Union Hospital TongJi Medical College HuaZhong University of Science and Technology, 1277 Jiefang Avenue, Jianghan District, Wuhan, Hubei, People’s Republic of China, Tel +86 13986074846, Email 8735174@qq.com
Background: With the rapid aging of China’s population, osteoporosis and sarcopenia have become major public health challenges. Denosumab, a first-line therapy for osteoporosis, may also improve muscle health, a possibility warranting further investigation.
Objective: This study evaluated the efficacy of denosumab in treating primary osteoporosis in the Chinese population and explored its potential effects on sarcopenia. A Mendelian randomization (MR) analysis was additionally performed to investigate the causal role of the RANKL pathway in sarcopenia.
Methods: This study included two components. In the clinical study, 45 patients with primary osteoporosis received denosumab, of whom 40 completed a 6-month follow-up and 15 completed a 1-year follow-up. Outcomes included bone turnover markers, bone mineral density, muscle strength, and physical performance measures. In the genetic study, two-sample MR was conducted using genome-wide association study (GWAS) summary statistics to assess the causal association between RANKL gene variants and sarcopenia-related traits, including appendicular lean mass and grip strength.
Results: Denosumab significantly reduced bone turnover markers and improved muscle function after 6 months, with further gains in bone mineral density and muscle strength observed at 1 year (all P < 0.05). Muscle mass showed upward but non-significant trends. MR analysis revealed a significant negative association between RANKL expression and both appendicular lean mass and grip strength, with no evidence of heterogeneity or pleiotropy.
Conclusion: Denosumab effectively treats osteoporosis and improves muscle function in Chinese patients. Genetic evidence supports a causal role of the RANKL pathway in sarcopenia, indicating that RANKL overexpression may contribute to its development. By integrating clinical and genetic evidence, our findings suggest that denosumab may represent a promising therapeutic option for patients with concurrent osteoporosis and sarcopenia.
Keywords: osteoporosis, sarcopenia, denosumab, RANKL gene, Mendelian randomization
1Union Hospital TongJi Medical College HuaZhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Geriatric hospital Affiliated to Wuhan University of science and technology, Wuhan, Hubei, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Wen Peng, Union Hospital TongJi Medical College HuaZhong University of Science and Technology, 1277 Jiefang Avenue, Jianghan District, Wuhan, Hubei, People’s Republic of China, Tel +86 13986074846, Email pengwen666@sina.com Jingjing Wan, Union Hospital TongJi Medical College HuaZhong University of Science and Technology, 1277 Jiefang Avenue, Jianghan District, Wuhan, Hubei, People’s Republic of China, Tel +86 13986074846, Email 8735174@qq.com
Background: With the rapid aging of China’s population, osteoporosis and sarcopenia have become major public health challenges. Denosumab, a first-line therapy for osteoporosis, may also improve muscle health, a possibility warranting further investigation.
Objective: This study evaluated the efficacy of denosumab in treating primary osteoporosis in the Chinese population and explored its potential effects on sarcopenia. A Mendelian randomization (MR) analysis was additionally performed to investigate the causal role of the RANKL pathway in sarcopenia.
Methods: This study included two components. In the clinical study, 45 patients with primary osteoporosis received denosumab, of whom 40 completed a 6-month follow-up and 15 completed a 1-year follow-up. Outcomes included bone turnover markers, bone mineral density, muscle strength, and physical performance measures. In the genetic study, two-sample MR was conducted using genome-wide association study (GWAS) summary statistics to assess the causal association between RANKL gene variants and sarcopenia-related traits, including appendicular lean mass and grip strength.
Results: Denosumab significantly reduced bone turnover markers and improved muscle function after 6 months, with further gains in bone mineral density and muscle strength observed at 1 year (all P < 0.05). Muscle mass showed upward but non-significant trends. MR analysis revealed a significant negative association between RANKL expression and both appendicular lean mass and grip strength, with no evidence of heterogeneity or pleiotropy.
Conclusion: Denosumab effectively treats osteoporosis and improves muscle function in Chinese patients. Genetic evidence supports a causal role of the RANKL pathway in sarcopenia, indicating that RANKL overexpression may contribute to its development. By integrating clinical and genetic evidence, our findings suggest that denosumab may represent a promising therapeutic option for patients with concurrent osteoporosis and sarcopenia.
Keywords: osteoporosis, sarcopenia, denosumab, RANKL gene, Mendelian randomization