Risk factors for knee osteoarthritis that may attribute to systemic or local leptin biosythesis
Obesity and the female sex represent significant risk factors for osteoarthritis (OA). Few studies have demonstrated a metabolic link between obesity and OA, strengthening the likelihood that biomechanical factors mediate this relationship, possibly via the redistribution of increased body mass to weight-bearing joints. However, it is less plausible that the biomechanical factors that contribute toward the incidence of OA at weight-bearing joints, such as the knee, are similar to those at non-weight bearing joints, such as in the hand. This may suggest that non-examined or unidentified biomechanical and/or systemic factors may be important contributors to the aetiology of OA. Recent developments that have helped to better appreciate the pathophysiology of obesity offer new hope to understanding the link between obesity and OA. The discovery of the obesity gene (ob) and its product leptin may have important implications for the onset and progression of OA. For instance, the greater total body fat of the average adult female may partially account for the gender disparity toward OA, given that females theoretically demonstrate higher levels of adipose derived systemic leptin concentrations than their male counterparts. However, while it was previously thought that adipose cells were only capable of leptin production, osteoblasts and chondrocytes are also capable of leptin synthesis and secretion, inferring that local leptin production may be of great importance. For instance, significant levels of leptin were observed in the cartilage and osteophytes of people with OA, yet few chondrocytes produced leptin in the cartilage of healthy people. Leptin has also been demonstrated to induce anabolic activity in the chondrocytes of rats, which may ultimately confer structural joint changes. This paper hypothesizes that leptin may be an unexamined systemic or local factor that may mediate the metabolic link between obesity and OA and partially account for the gender disparity toward the disease.
Teichtahl AJ, Wluka AE, Proietto J, Cicuttini FM. Obesity and the female sex, risk factors for knee osteoarthritis that may be attributable to systemic or local leptin biosynthesis and its cellular effects. Med Hypotheses. 2005 December Department of Epidemiology and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, Victoria 3004, Australia.