Weekend Warrior Physical Activity Pattern, Metabolomic Profiles, and Risk of Osteoporosis and Fracture

BACKGROUND & AIMS: The weekend warrior pattern, characterized by infrequent but sufficient bouts of moderate-to-vigorous physical activity (MVPA), has become increasingly common. Its association with the risk of osteoporosis and fracture remains unclear. We aimed to examine the association between the weekend warrior pattern and bone outcomes, identify related metabolites, and assess the modifying role of genetic susceptibility. METHODS: We included 14,069 UK Biobank (UKB) participants with accelerometer and metabolomic data. Metabolomic signatures corresponding to weekend warrior and regular physical activity patterns were identified using elastic net regression. Cox proportional hazards models were used to examine the associations of physical activity patterns and metabolomic profiles with osteoporosis and fracture risk. Stratified analyses by polygenic risk scores (PRS) for osteoporosis and fracture were conducted to evaluate the potential effect modification by genetic susceptibility. RESULTS: During a median follow-up of 7.8 years, 267 cases of osteoporosis and 554 fracture events were documented. In comparison with the inactive group, the weekend warrior pattern was significantly associated with reduced risks of osteoporosis (HR: 0.59; 95% CI: 0.44-0.79) and fracture (HR: 0.77; 95% CI: 0.63-0.95). Using elastic net regression, we identified 51 metabolites characterizing the weekend warrior pattern and 62 metabolites representing regular physical activity. Each standard deviation (SD) increase in the weekend warrior-related metabolomic signature corresponded to a 27% lower risk of osteoporosis (HR: 0.73; 95% CI: 0.62-0.85) and a 12% lower risk of fracture (HR: 0.88; 95% CI: 0.79-0.99). These associations were not significantly modified by genetic susceptibility to osteoporosis (P = 0.429) or fracture (P = 0.221). CONCLUSIONS: The weekend warrior pattern was associated with lower risks of osteoporosis and fracture. We further identified distinct metabolomic signature characterizing this pattern, providing potential mechanistic insights into its protective effects.