Sexual dimorphism in knee osteoarthritis: Biomechanical variances and biological influences

Abstract

Objective: Osteoarthritis (OA) is a degenerative joint disease that is more prevalent in women than men, especially later in life. This suggests that sexual dimorphism may be present in the pathogenesis of the disease. The purpose of this review is to discuss evidence of sexual dimorphism in knee OA development and presentation as it is framed by two contrasting paradigms: biomechanics and biology.

Methods: A comprehensive search of databases was conducted including, but not limited to, MEDLINE via Ovid, PubMed, and Google Scholar. Keywords including osteoarthritis, sex differences, and/or sexual dimorphism were searched in combination with knee biomechanics, ACL, joint malalignment, estrogen, chondrocyte signal(l)ing, growth factor and integrin(s).

Results: The biomechanical approach has identified sex differences in joint malalignment, bone shape, gait, and lower limb muscle strength leading to altered load transmission, as well as increased knee laxity in women predisposing them to joint injury. The biological approach has largely focused on the influence of estrogen receptor signaling on the maintenance of joint tissues. Preliminary work identifying sexual dimorphism in chondrocyte signaling pathways involving growth factors and collagen receptors has been reported in addition to more systemic levels of inflammatory cytokines and metabolites.

Conclusion: Understanding the true etiology of OA is crucial for developing effective, individualized treatment in the age of personalised medicine. A shift from a 'one size fits all' mentality towards an individualized approach for therapeutic treatment must begin with the acknowledgment of sex differences in the biomechanical and biological factors underlying the onset and development of OA.

Keywords: ACL, Anterior Cruciate Ligament; Biomechanics; Cell signaling; EGFR, Epidermal Growth Factor Receptor; ER, Estrogen Receptor; Knee; OA, Osteoarthritis; Osteoarthritis; Sexual dimorphism.