Abstract
BACKGROUND: The prevalence of hyperuricemia is rising among young adults, yet its impact on bone metabolism remains unclear. This study investigated the association between serum uric acid levels and spinal bone mineral density in adults under 50, evaluating confounders, effect modification, and mediating pathways. METHODS: This cross-sectional study at the First People's Hospital of Changde City (January 1-December 31, 2024) included 238 individuals aged <50 years. Serum uric acid was the exposure; lumbar spine Z-score was the outcome. Multivariable linear regression assessed associations after adjusting for age, sex, creatinine, alanine aminotransferase, total cholesterol, neutrophil count, red blood cell count, waist circumference, triglycerides, and blood pressure. Stratified analyses examined effect modification; mediation analysis quantified creatinine's role. RESULTS: Adjusted models showed each 100 μmol/L increase in serum uric acid was associated with a 0.20 higher lumbar spine Z-score.(β = 0.002, 95 % CI: 0.000-0.004, P = 0.044). The association was significant in women (β = 0.004 per μmol/L, P = 0.009) but absent in men (β = -0.001, P = 0.712), and stronger with lower creatinine (P_interaction = 0.004) or waist circumference (P_interaction = 0.004). Creatinine mediated 49.3 % of the effect (average mediation effect = 0.161, 95 % CI: 0.004-0.562, P = 0.024; direct effect P = 0.160). CONCLUSIONS: Higher serum uric acid levels are associated with increased spinal bone mineral density in adults under 50, mediated partly by creatinine (∼49 % of the effect), with stronger effects in women and those with better renal function and lower adiposity. These findings reposition uric acid as a potential early protector against bone loss, paving the way for sex- and metabolism-tailored interventions to prevent osteoporosis in younger populations.