Sex and Gender in Rheumatic and Musculoskeletal Diseases: Bridging Biological Mechanisms and Clinical Outcomes

Sex and gender are increasingly recognized as fundamental determinants in rheumatic and musculoskeletal diseases (RMDs), yet their influence remains incompletely understood and unevenly translated into clinical practice. While sex refers to biological attributes shaped by chromosomes, hormones and reproductive physiology, gender includes the sociocultural roles, behaviours and identities that condition how patients experience disease and interact with health systems. Many autoimmune conditions, including systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome and systemic sclerosis, display a marked female predominance, whereas other RMDs conditions, such as axial spondyloarthritis and gout, have historically been considered more frequent or more readily diagnosed in men. Sex hormones and X-linked immune genes modulate innate and adaptive immunity, contributing to differences in susceptibility, disease phenotype, activity and structural progression. Beyond biology, gender-related factors can shape the patient journey. Diagnostic delay, referral pathways, access to specialist care, health-seeking behaviour, treatment adherence and the burden of caregiving and work disability may differ between women and men, yet these differences remain poorly characterized. Sex differences in pharmacokinetics, treatment response and adverse events are frequently overlooked, while pain, fatigue and quality of life are experienced and reported differently across groups. Compounding these gaps, one sex has often been underrepresented in clinical trials and sex-disaggregated data are still not routinely collected or reported, limiting the evidence base needed for equitable, personalized care.This Research Topic aims to investigate the role of sex and gender across RMDs, promoting the exchange of clinical experience and scientific knowledge to address current gaps. A further core objective is to promote sex- and gender-sensitive research design and reporting as a standard in rheumatology. We welcome contributions covering, but not limited to, the following themes:• Sex hormones, the immune system and the pathogenesis of rheumatic diseases• Genetic, epigenetic and X-chromosome contributions to sex differences in autoimmunity• Sex- and gender-based differences in the epidemiology and clinical phenotype of RMDs• Sex differences in disease activity, structural damage and long-term outcomes• Gender disparities in diagnostic delay, referral pathways and access to care• Sex and gender differences in treatment response, drug pharmacokinetics and adverse events• Pain, fatigue and health-related quality of life across sex and gender• Reproductive health, pregnancy and menopause in RMDs• Cardiovascular, bone and metabolic comorbidities from a sex- and gender-based perspective• Gender dimensions of work disability, caregiving and psychosocial burden• Methodological approaches to sex- and gender-sensitive study design and sex-disaggregated dataOriginal article types are welcome and may include original research, study protocols, reviews and systematic reviews. Topic editors: Maria Chiara Maccarone, Gabriel Dias Rodrigues, Martin Offenbächer, Stefano Gentileschi Source: https://www.frontiersin.org/research-topics/85068/sex-and-gender-in-rheumatic-and-musculoskeletal-diseases-bridging-biological-mechanisms-and-clinical-outcomes