Sarcopenia and Osteosarcopenia in Primary Biliary Cholangitis: A Systemic Perspective and the Role of PPAR Agonists

Primary biliary cholangitis (PBC) is a systemic disease in which musculoskeletal complications may impair function despite satisfactory biochemical control. This narrative review integrates PBC-specific evidence on sarcopenia, osteoporosis and osteosarcopenia with mechanistic studies of cholestasis, muscle-bone interactions and peroxisome proliferator-activated receptor (PPAR) signalling. Muscle depletion occurs before cirrhosis, but heterogeneous definitions and retrospective designs limit prevalence estimates and prognostic interpretation. Population-based studies link PBC to fractures and increased post-fracture mortality, whereas dedicated osteosarcopenia studies remain limited. Nutritional compromise, inflammation, endocrine abnormalities, symptom-related inactivity and advanced liver disease converge on the muscle-bone unit. General densitometric and fracture-risk frameworks remain necessary because PBC-specific integrated thresholds are unvalidated. PPAR agonists improve biochemical activity and, for some agents, symptoms, but their musculoskeletal effects must be considered separately by receptor isoform. Experimental oxidative adaptation and exploratory bone-density findings do not establish sarcopenia reversal or fracture protection; fracture signals and potential muscle toxicity require independent assessment. Ileal bile acid transporter inhibition offers pruritus relief but also requires attention to fat-soluble vitamins and skeletal safety. Integrated evaluation of symptoms, strength, body composition, physical performance and fracture risk may identify actionable limitations. Prospective cohorts and controlled interventions with predefined musculoskeletal endpoints are needed to establish clinically meaningful benefit.