Loneliness, traditional risk factor control, genetic predisposition, and development of musculoskeletal disorders

Abstract Objectives To investigate prospective associations of loneliness and social isolation with musculoskeletal (MSK) disorder risk, evaluate their relative importance vs traditional risk factors, and assess interactions with genetic predispositions. Methods : We analyzed data from 315 197 UK Biobank participants. Loneliness and social isolation were assessed through self-reported questionnaires. The primary outcome was the incidence of any MSK disorder, with secondary outcomes comprising five specific MSK conditions of high burden [osteoarthritis, gout, rheumatoid arthritis, low back pain, and neck pain]. Cox regressions were performed to examine the associations between loneliness, social isolation, traditional risk factor control, polygenic risk score and risk of overall and specific MSK disorders. Results During a median follow-up of 13.3 years, 79 689 MSK cases were documented. Loneliness (HR = 1.14, 95% CI = 1.11–1.17) was associated with an increased risk of overall MSK disorders, whereas social isolation was associated with a modestly lower risk (HR = 0.96, 95% CI = 0.94–0.99). Loneliness ranked higher in relative strength than most of the traditional risk factors. Significant interactions on both additive and multiplicative scales between loneliness and traditional risk factor control were observed. When stratified by genetic risk, loneliness was consistently associated with an increased risk of overall MSK disorders across strata. Joint analysis indicated the absence of loneliness to offset the genetic risk of overall MSK disorders. When extending to five specific conditions, largely consistent patterns of results were observed. Conclusion Loneliness is associated with increased MSK disorder risk, shows an interaction with the degree of risk factor control, and may modify genetic predisposition. These findings support targeting loneliness to reduce the burden of MSK disorders.