A Distinct Serum Metabolic Profile Characterizes Osteosarcopenia: Identifying Potential Metabolic Biomarkers

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Background: Osteosarcopenia, the concurrent presence of osteoporosis and sarcopenia, is associated with elevated fracture risk, frailty, and mortality. Early molecular characterization may enable timely intervention. This study aimed to define a distinct serum metabolic signature of osteosarcopenia and identify candidate biomarkers. Methods: A cross-sectional study enrolled 340 community-dwelling adults aged ≥60 years, classified into four groups: robust (n=120), osteoporosis alone (n=85), sarcopenia alone (n=72), and osteosarcopenia (n=63). Untargeted and targeted serum metabolomics (LC-MS/MS) quantified amino acids, lipids, acylcarnitines, and related metabolites. Clinical assessments included dual-energy X-ray absorptiometry (DXA), handgrip strength, gait speed, and skeletal muscle index (SMI). Multivariate analyses and ROC curves evaluated discriminatory performance. Results: Osteosarcopenia exhibited a unique metabolic profile characterized by reduced branched-chain amino acids (leucine ↓32%, isoleucine ↓29%, valine ↓26%), lower creatinine, elevated citrulline, and altered phospholipid species (notably elevated PI 32:1 and reduced PC species). Pathway enrichment highlighted BCAA metabolism, lipid remodeling, and steroid biosynthesis. Key individual biomarkers showed AUCs of 0.71–0.82; a combined five-metabolite panel achieved AUC 0.91 (95% CI 0.86–0.95) for distinguishing osteosarcopenia from robust controls. Metabolite levels correlated significantly with SMI and bone mineral density. Conclusion: Osteosarcopenia is characterized by a distinct serum metabolic fingerprint involving amino acid catabolism, lipid dysregulation, and inflammatory shifts. Creatinine, leucine, PI 32:1, and a multi-metabolite panel emerge as promising biomarkers for early detection and phenotyping of this high-risk geriatric syndrome.

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