R1: Sexual Dimorphism in Articular Tissue Anatomy - Key to Understanding Sex-differences in Osteoarthritis?

Osteoarthritis (OA) prevalence and incidence varies between women and men, but it is unknown whether this follows sex-specific differences in systemic factors (e.g. hormones), and/or differences in pre-morbid joint anatomy. We recognize that classifications of sex within humans cannot be reduced to female/male, but given the lack of literature on non-binary individuals, this review is limited to the sexual dimorphism of articular tissues. Based on a Pubmed search using relevant terms, and input from experts, we selected articles based on the authors' judgement of their relevance, interest, originality, and scientific quality; no "hard" bibliometric measures were used to evaluate their quality or importance. Focus was on clinical rather than pre-clinical studies, with most (imaging) data being available for the knee joint. After introducing "sexual dimorphism", the specific literature on articular structures is reviewed, structured by: radiographic joint space width (JSW), meniscus, ligaments, articular cartilage metrics, articular cartilage composition and deformation, and articular tissue response to treatment. Sex-specific differences were clearly observed for JSW, meniscus damage, ligament size, and cartilage metrics (volume, thickness and surface areas), but not for cartilage composition. Ligament and cartilage metrics were smaller in women even after matching for confounders. Taken together, the findings indicate that female (knee) joints may be structurally more vulnerable and at greater risk of OA. The "one size/sex fits all" approach must be abandoned in OA research, and all observational and interventional studies should report their results for sex-specific strata, at least in pre-specified secondary or post-hoc analyses.