Serum creatinine, genetic susceptibility, and the risk of osteoporosis and fracture: a prospective cohort study from the UK Biobank

Background: Osteoporosis imposes a substantial fracture burden, yet scalable and dynamic biomarkers for risk stratification remain limited. Serum creatinine-routinely assayed and capturing intertwined muscle and renal signals-has been little studied for incident osteoporosis or fractures. Methods: In the UK Biobank, covariate-adjusted Cox models and restricted cubic splines assessed associations of baseline creatinine with incident osteoporosis and fractures. Creatinine was modeled categorically (six strata; G4 [70-80 μmol/L] as reference) and continuously. The pre-defined analysis was stratified by sex and age (>65) as well as the three tertiles of the polygenic risk score for osteoporosis (PRS); the multiplicative interaction term examined the relationship between creatinine and PRS. Results: Creatinine showed a U-shaped association with osteoporosis, with a nadir near 80 μmol/L (overall P