The Influence of Serum Uric Acid on Bone Mineral Density, Hip Geometry, and Fracture Risk: The Rotterdam Study

Context: The role of uric acid (UA) in skeletal metabolism remains to be unraveled. Objective: We prospectively investigated the association between UA, bone mineral density at the femoral neck (FN-BMD), hip bone geometry parameters, and incident fracture risk and examined whether the associations were modified by age and vitamin C intake. Participants and Setting: Data of 5074 participants of The Rotterdam Study, a prospective population-based cohort. Exposure: Serum UA was assessed at baseline. Main Outcomes and Measures: FN-BMD was measured at baseline, and at second, third, and fourth visits of the Rotterdam Study. Hip bone geometry parameters were measured at baseline and at the second and third visits. Results: Serum UA levels (per SD increase) were positively associated with FN-BMD (beta = 0.007 g/cm(2); 95% confidence interval [CI] = 0.002-0.01), thicker cortices (beta = 0.002 cm; 95% CI = .0003-0.002), lower bone width (beta = -.013 cm; 95% CI = -0.23 to -0.003), and lower cortical buckling ratio (beta = -0.19; 95% CI = -0.33 to -0.06). The effects of UA on FN-BMD and cortical buckling ratio tended to become stronger over time. Hazard ratios and 95% CIs per SD increase of baseline UA levels for the development of any type of incident fractures, nonvertebral fractures, and osteoporotic fractures were 0.932 (0.86-0.995), 0.924 (0.856-0.998), and 0.905 (0.849-0.982), respectively. These associations were more prominent in older individuals (age, >65 y) and in participants with high intakes of vitamin C (> median). Conclusions: Higher levels of serum UA are associated with higher BMD (at the expense of thicker cortices and narrower bone diameters) and may be a protective factor in bone metabolism. However, interactions with age and vitamin C may be present.