Serum uric acid and bone mineral density: Reappraising an overstated association

A recent acceleration in NHANES-based serum uric acid (SUA) and bone mineral density (BMD) publications has encouraged recommendations to relax the treatment target for hyperuricemia, possibly placing patients at higher risk for gout. We reappraised pooled 2005-2018 NHANES data to determine whether SUA supports a clinically meaningful bone-protective role. Survey-weighted analyses of 3687 to 6039 participants assessed the influence of SUA on BMD at 10 anatomical sites, with femoral neck and total lumbar spine BMD as co-primary outcomes, as well as osteoporosis and fragility fracture. Higher SUA was nominally associated with slightly higher total lumbar spine BMD (βˆ=0.0062, 0.0003-0.0122, P=0.042) but not femoral neck BMD (βˆ=0.0035, -0.0006-0.0076, P=0.093). Allometric analyses revealed a similar pattern. Restricted cubic splines depicted a linear association at the lumbar spine and a nonlinear femoral neck association which flattened near the SUA solubility limit of 6.8 mg/dL. Importantly, all clinical end points were null; SUA was not associated with osteoporosis or fragility fracture in the primary continuous models (ORs 0.960 to 1.007; all P≥0.743). Alternative thresholds, quintile trends, and sensitivity analyses showed no consistent association. Higher SUA was not associated with femoral neck BMD or total lumbar spine BMD across 18/21 and 13/21 sensitivity tests, respectively. Notably, when 24-hour dietary intake was considered in sensitivity analyses, none of the outcomes maintained statistical significance. Thus, modest site-specific associations between SUA and BMD did not translate into clinical benefit. These findings do not support a direct bone-protective role for SUA or relaxation of the 6.0 mg/dL hyperuricemia treatment target.