Obesity, Exercise and Osteoarthritis: Exploring the Role of Muscle-Derived Signals

Dr. Shehla Shaikh, Dept. of Endocrinology, Saifee Hospital and HN Reliance Hospital, Mumbai, India

Weight management and regular physical activity remain central to osteoarthritis care, while muscle-derived signalling molecules may offer further insights into the relationship between exercise, inflammation and joint health.

Osteoarthritis (OA) is a leading cause of pain and disability worldwide, particularly among older adults. Obesity is an important modifiable risk factor, contributing to disease progression through increased mechanical stress on joints and chronic low-grade inflammation. Excess body weight is associated with greater knee OA risk, more severe pain, and poorer physical function. Evidence also suggests that weight loss can reduce the risk of joint replacement, highlighting the importance of weight management in long-term care.

A combination of dietary intervention and physical exercise may offer greater benefits than dietary changes alone. Exercise improves muscle strength, supports joint stability and may influence inflammatory pathways. Skeletal muscles also release myokines, signalling molecules that could help explain some of the benefits of physical activity beyond weight reduction.

Among these molecules, irisin has attracted interest for its potential anti-inflammatory and cartilage-protective effects. Laboratory and animal studies suggest that it may reduce inflammatory signalling and support cartilage metabolism. However, findings from human studies remain inconsistent, and its role in improving OA outcomes has not been established. Similarly, interleukin-6 (IL-6) has complex, context-dependent effects. Although persistently elevated systemic IL-6 is associated with inflammation, the transient release of IL-6 during muscle contraction may have different metabolic and immunomodulatory effects.

Current evidence supports weight management and exercise as important components of OA management, but the contribution of individual myokines remains uncertain. Further clinical research is needed to establish whether these molecules directly mediate exercise-related benefits or primarily reflect changes in physical activity and inflammation. Understanding these pathways could eventually help refine strategies for preserving joint function and improving quality of life in people living with OA.

(Source: Pysiewicz M, Budzik P, Stadnicka O, Malaya E, Mokrzecki S, Wolnik JE, Grzywacz M. The role of myokines in obesity-related osteoarthritis: linking physical activity to joint health. Quality in Sport. 2026 Apr 19;54:70696-. )