Obesity-Related Tendon Pathology: Cardiometabolic Mechanisms, Clinical Implications, and Management

This review evaluates obesity as the organizing exposure linking mechanical loading and adipose-tissue dysfunction with tendon pathology. It synthesizes site- and outcome-specific human evidence, candidate mechanisms, tendon xanthomas associated with familial hypercholesterolemia (FH), and implications for targeted assessment and management.

Human studies associate obesity and related cardiometabolic abnormalities with tendinopathy, tendon rupture, and postoperative outcomes, but findings vary by exposure, site, and outcome and remain predominantly observational. Limited human tissue and predominantly preclinical studies support candidate roles for glycation, oxidized lipids, chronic inflammation, mitochondrial and redox dysfunction, and impaired repair, although their causal sequence and human relevance remain uncertain. Recent single-cell and spatial studies reveal tendon cellular heterogeneity but have not established obesity- or metabolism-specific endotypes. Recurrent, bilateral, atraumatic, or treatment-resistant manifestations have been proposed as features of a hypothesis-generating "metabolic tendon phenotype" rather than a validated diagnostic entity. FH-related tendon xanthomas represent a distinct manifestation of severe cumulative low-density lipoprotein cholesterol exposure. Standard tendon-directed rehabilitation remains central, whereas tendon-specific benefits of cardiometabolic optimization, glucagon-like peptide-1 receptor agonists, bariatric surgery, or lipid-lowering therapy remain unconfirmed. The proposed mechanometabolic continuum integrates obesity-associated systemic influences with local loading as a conceptual framework rather than a validated disease model or screening tool. Current evidence does not support universal cardiometabolic or cardiovascular screening based on nonspecific tendinopathy alone; targeted assessment may be considered in selected patients with relevant clinical cues or conventional risk factors. Longitudinal human studies and intervention trials are needed to clarify causality and clinical utility.