Closing the gap: sex-related differences in osteoarthritis and the ongoing need for translational studies

Abstract

Clinical insights into sex-related differences in osteoarthritisInitially, it was believed that molecular and cellular mechanism found in a species were ubiquitous amongst its members, regardless of age, sex or other inter-individual factors.Over the last few decades, a paradigm shift has occurred with researchers and clinicians backing away from generalisation and moving towards a personalized approach.Ongoing research efforts have focused on identifying differences in the pathogenesis, prevalence, incidence, and severity of a given disease based on inter-individual factors.A sexual dimorphism has been established across a wide variety of processes (including genetic, molecular, cellular, clinical and psychological) during both health and disease.Unfortunately, in the field of degenerative joint disease, and particularly osteoarthritis (OA), the understanding of the influence of sex on disease is still limited (1).This is partially due to a historical perception that OA was simply caused by "wear and tear" with the majority of research focusing on biomechanical causes of disease.More recently, several studies have explored the intricate biological processes that contribute towards the pathogenesis of OA; findings support that it is a far more complex pathology than initially believed (2).For almost four decades, researchers have reported sex-related differences in the clinical presentation and prevalence of OA (3).Clinical evidence has emerged that women over the age of 55 years have a higher prevalence of knee OA than men (4).In addition, women suffer from more debilitating pain (4), rapidly progressing annual articular cartilage loss (4 times the rate in comparison to men) (5) and a more severe radiographic OA phenotype than men (4).Sex hormones, such as estrogen, have been shown to mitigate pain and exert protective roles on articular cartilage biochemistry (5).Therefore, researchers postulate estrogen loss in postmenopausal women may explain the exacerbated progression of OA (5).To date, no prophylactic or disease modifying drug is available for clinical use; the only established long-term treatment remains joint replacement using arthroplasty.Consequently, the Osteoarthritis Research Society International (OARSI) still considers OA to be an incurable disease (6).However, recent studies have shown that men achieve better and faster functional recovery, while women have a favourable prognosis with respect to implant

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