DOI: 10.3390/metabo16080547 ISSN: 2218-1989

Rhythmic Metabolism in Osteosarcopenia: Emerging Evidence, a Chronometabolomic Framework for the Bone–Muscle Unit, and Research Priorities

Yirui Chen, Hongxin Gui, Mingyuan Liu, Sitong Liu, Chang Liu, Yuqing Xue

Osteosarcopenia combines low bone mass or skeletal fragility with sarcopenia, yet its metabolic biology is commonly assessed using single-time-point measurements. We conducted a structured narrative review of PubMed/MEDLINE, Web of Science Core Collection, Embase and Scopus from inception through 28 June 2026, supplemented by ScienceDirect, Google Scholar and citation chaining. Evidence was classified as direct human osteosarcopenia evidence, indirect human evidence, preclinical evidence or conceptual inference. Here, chronometabolomics denotes time-anchored or repeated metabolomic profiling used to estimate variation in phase, amplitude and pathway coordination in relation to sleep, feeding, activity and endocrine timing. Direct human evidence remains scarce. Component-specific human studies and experimental models suggest, but do not establish, that aging, chronic disease and irregular schedules may alter glucose–insulin, amino-acid, lipid, mitochondrial, redox-inflammatory, mineral-endocrine and microbial rhythms relevant to the bone–muscle unit. Chronometabolomics is therefore an emerging research framework, not a validated diagnostic or therapeutic approach. Daytime light, sleep regularization, protein distribution, time-restricted eating, exercise timing and medication timing remain candidates for controlled trials rather than current clinical recommendations; safety evaluation must address frailty, low body mass index, malnutrition, kidney disease, diabetes, polypharmacy, falls and inadequate protein or calcium intake.

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