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Despite the acknowledgment of muscle-bone crosstalk, the underlying mechanism driving their simultaneous decline remains poorly understood, resulting in a lack of effective integrated therapies. This review aims to elucidate the \u201cinflammation-energy metabolism axis\u201d as the central driver of this condition. This review contends that sarcopenia-osteoporosis is not a coincidental comorbidity but a single pathological syndrome driven by the failure of the inflammation-energy metabolism axis. Its pathophysiology is a self-sustaining vicious cycle where chronic low-grade inflammation (inflammaging) and dysregulated energy metabolism (notably mitochondrial dysfunction and insulin resistance) reciprocally amplify each other, leading to synchronous muscle and bone deterioration. The review first details how chronic inflammation, via pathways like NF-\u03baB and the NLRP3 inflammasome, promotes muscle catabolism and bone resorption. Second, it explains how an energy crisis, stemming from mitochondrial damage and insulin resistance, impairs anabolic processes in both tissues. Finally, the underlying cycle is revealed: inflammation disrupts metabolic pathways (e.g., PI3K\/AKT\/mTOR), while metabolic stress releases DAMPs that further fuel inflammation, trapping the muscle-bone unit in a catabolic state. Understanding this central axis necessitates a paradigm shift from single-target treatments to systemic interventions. Future strategies should focus on disrupting this vicious cycle through combination therapies (e.g., anti-inflammatory and pro-metabolic agents), gut microbiota modulation, and exercise, offering novel approaches to this debilitating comorbidity.<\/jats:p>","DOI":"10.1007\/s00223-025-01473-8","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T02:55:32Z","timestamp":1767754532000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The Inflammation-Energy Metabolism Axis: A Central Driver of Sarcopenia-Osteoporosis: A Narrative Review"],"prefix":"10.1007","volume":"117","author":[{"given":"Yifan","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijian","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingtao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibo","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosheng","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxiang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"1473_CR1","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.jocd.2009.06.004","volume":"12","author":"N Binkley","year":"2009","unstructured":"Binkley N, Buehring B (2009) Beyond FRAX\u00ae: it\u2019s time to consider sarco-osteopenia. 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