Osteoarthritis as a Failure of Adaptation: Biological Complexity and the Therapeutic Role of Physical Activity

Abstract

Osteoarthritis (OA) is the most prevalent musculoskeletal disorder worldwide and a leading cause of chronic pain, disability, and reduced quality of life. Traditionally conceptualized as a degenerative condition driven by mechanical wear and age-related structural deterioration of articular cartilage, this paradigm does not adequately explain the heterogeneity of clinical presentation, the weak correlation between structural damage and pain, or the limited efficacy of many current therapeutic strategies. Growing evidence supports a conceptual shift in which osteoarthritis is understood as a biologically active disorder of impaired adaptation. Within this framework, OA reflects the reduced capacity of joint tissues to maintain homeostasis in response to cumulative mechanical, metabolic, and inflammatory stressors. Rather than representing an inevitable consequence of aging or mechanical overload alone, osteoarthritis can be interpreted as a failure of coordinated adaptive responses across the whole joint organ. This narrative review aims to synthesize current evidence from inflammation biology, mechanotransduction, and epigenetic regulation to develop an integrative model of osteoarthritis as diminished adaptive capacity. Physical activity is examined as a biologically active intervention capable of modulating inflammatory tone, restoring mechanosensitivity, and supporting functional resilience. This review is based on a structured, non-systematic literature search conducted in PubMed and Scopus, focusing on publications addressing osteoarthritis, inflammation, mechanobiology, epigenetic regulation, and physical activity. Emphasis was placed on high-quality reviews, mechanistic experimental studies, and clinically relevant translational research published predominantly within the past 15 years, alongside seminal foundational work.