Social Isolation and Loneliness Elevating Osteoporosis and Fracture Morbidity, Mediated by Frailty and Systemic...

Osteoporosis (OP) and fractures impose an increasingly heavy burden on aging populations. The social isolation and loneliness commonly experienced by older adults may influence skeletal health through multiple pathways. Therefore, we aim to examine the associations of social isolation and loneliness with the risk of OP and fractures.

We included 432,635 participants from the UK Biobank cohort, with 14,810 OP and 21,758 fracture incident cases during a 14.8-year (median) follow-up. Associations between social isolation and loneliness with incident OP and fracture risks were analyzed by using Cox regression models. With polygenetic risk scores constructed by genome-wide significant genetic variants, we analyzed joint and interaction effects of social isolation and loneliness and genetic predisposed OP and fracture risk. Mediation effects of frailty and systemic inflammation were also explored.

Social isolation and loneliness were associated with increased hazards of OP [hazard ratio (HR)=1.12 (95% CI=1.07-1.19) and 1.19 (1.11-1.28), respectively] and fractures [1.11 (1.07-1.17) and 1.18 (1.12-1.26), respectively]. Genetic predispositions did not modify the associations. Frailty and systemic inflammation mediated their effects with 0.68% to 36.87% of total effects for social isolation, loneliness, and OP, and 0.45% to 23.17% of total effects for social isolation, loneliness, and fractures. Subgroup and sensitivity analyses confirmed the robustness of these findings.

Social isolation and loneliness contribute to OP and fracture incidence, partially mediated by frailty and systemic inflammation. Our findings implicated the importance of strengthening social connection and target intervention of against frailty in OP and fracture prevention.