Gender and Sex Are Key Determinants in Osteoarthritis Not Only Confounding Variables. A Systematic Review of Clinical Data

Abstract

Many risk factors for osteoarthritis (OA) have been noted, while gender/sex differences have been understated. The work aimed to systematically review literature investigating as primary aim the relationship between gender/sex related discriminants and OA. The search was performed in PubMed, Science Direct and Web of Knowledge in the last 10 years. Inclusion criteria were limited to clinical studies of patients affected by OA in any joints, analyzing as primary aim gender/sex differences. Exclusion criteria were review articles, in vitro, in vivo and ex vivo studies, case series studies and papers in which gender/sex differences were adjusted as confounding variable. Of the 120 records screened, 42 studies were included. Different clinical outcomes were analyzed: morphometric differences, followed by kinematics, pain, functional outcomes after arthroplasty and health care needs of patients. Women appear to use more health care, have higher OA prevalence, clinical pain and inflammation, decreased cartilage volume, physical difficulty, and smaller joint parameters and dimensions, as compared to men. No in-depth studies or mechanistic studies analyzing biomarker differential expressions, molecular pathways and omic profiles were found that might drive preclinical and clinical research towards sex-/gender-oriented protocols.

Gender-Related Aspects in Osteoarthritis Development and Progression: A Review

“…The factors that might contribute to their susceptibility include thinner cartilage, tendency to varus malalignment, joint instability, and uneven mechanical loading. Furthermore, OA development can be triggered by the steep decline of sex hormone levels in the menopause [ 13 , 14 ]. Sex-related differences in the onset and progression of OA have been the subject of a number of studies, and there is increasing interest in this topic, with new data constantly brought to the attention of scientists [ 14 , 15 ].…”

“…Furthermore, OA development can be triggered by the steep decline of sex hormone levels in the menopause [ 13 , 14 ]. Sex-related differences in the onset and progression of OA have been the subject of a number of studies, and there is increasing interest in this topic, with new data constantly brought to the attention of scientists [ 14 , 15 ]. Therefore, the present review aims to provide an updated summary of the most recent evidence on the gender-related mechanisms of OA, including the hormone-determined, anatomical, molecular, and biomechanical aspects, as well as their interconnections.…”

Innate Immunity at the Core of Sex Differences in Osteoarthritic Pain?

“…In agreement, OA also affects a higher proportion of women than men ( Srikanth et al, 2005 ; Glass et al, 2014 ). Increasing numbers of researchers have focused on understanding sex differences in OA in the past decade from both the preclinical (for a systematic review, see ( Contartese et al, 2020 )) and clinical (for systematic review, see ( Tschon et al, 2021 )) perspectives. Even though hand OA is more prevalent in women ( Haugen et al, 2011 ), clinically, knee and hip OA have been the most investigated for sex differences ( Tschon et al, 2021 ).…”

“…Women reporting worse pain scenario ( Perruccio et al, 2017 ), increased VAS score ( Glass et al, 2014 ; Solheim et al, 2017 ), and lower pain threshold ( Pan et al, 2016 ) have been linked to an enhanced inflammatory response. Yet, despite the increase in researchers investigating these sex differences, the biological mechanisms behind these differences in OA pain appear to be understudied ( Tschon et al, 2021 ).…”

“… Summary of major clinical findings of sex differences in OA (adapted from ( Basbaum et al, 2009 ; Tschon et al, 2021 )). …”