Osteosarcopenia: The Hidden Dual Threat Accelerating Chronic Disease Outcomes

Osteosarcopenia (OS) refers to the simultaneous presence of osteopenia or osteoporosis alongside sarcopenia — the age-related loss of muscle mass and function. First introduced by Duque et al., OS represents a compounding musculoskeletal vulnerability that is increasingly recognized as a critical but underappreciated driver of poor health outcomes in elderly populations and those with chronic diseases. This 2025 narrative review synthesizes epidemiological data, molecular mechanisms, diagnostic frameworks, and management strategies for OS across major chronic disease categories.

Diagnostically, OS is identified by meeting criteria for both conditions simultaneously. Osteoporosis is confirmed by DXA-measured T-scores of ≤ -2.5 SD, while sarcopenia is assessed using the EWGSOP 2018 criteria, including grip strength, chair stand test performance, appendicular skeletal muscle mass thresholds, and gait speed ≤0.8 m/s. DXA is considered the gold standard for both bone and muscle assessment. Critically, no universally accepted diagnostic criteria for OS as a unified syndrome yet exist.

Epidemiologically, OS prevalence escalates dramatically with age: from 14.3% in men aged 60–64 to 59.4% in those ≥75, and from 20.3% to 48.3% in women across the same age range. Women show generally higher prevalence. Across chronic diseases, the consequences are severe. In liver cirrhosis, OS carries a hazard ratio of 4.798 for mortality. In primary biliary cholangitis, vertebral fracture incidence reached 55.6% in OS patients. In CKD, OS patients faced 33% higher mortality risk and more than double the risk of progressing to end-stage renal disease. In heart failure, OS was independently associated with a 17% increased risk of cardiac events. In COPD, OS compounds dyspnea and cachexia through mitochondrial dysfunction and muscle fiber type shifts.

Molecularly, the review emphasizes shared pathophysiological pathways linking bone and muscle deterioration: chronic systemic inflammation (elevated IL-6, TNF-α), disrupted IGF-1/mTOR signaling, hormonal decline (sex steroids, vitamin D), oxidative stress, mitochondrial dysfunction, and impaired mesenchymal stem cell (MSC) differentiation favoring adipogenesis over osteogenesis and myogenesis. Cross-talk between osteocytes and myocytes via paracrine signaling molecules such as irisin, myostatin, and osteocalcin is highlighted as a central mechanism underlying the co-deterioration of both tissues.

Management strategies discussed include resistance and aerobic exercise training, protein-rich nutrition (especially leucine and essential amino acids), vitamin D and calcium supplementation, anti-resorptive agents, and emerging cell-based therapies using MSCs. The review also underscores the urgent need for standardized OS screening protocols integrated into chronic disease management pathways, particularly in older adults.