Association between serum uric acid levels and osteoporosis risk: evidence from a cross-sectional study and Mendelian randomization analysis

Abstract

Objective: This study investigated the relationship between serum uric acid (SUA) levels and osteoporosis (OP) risk through cross-sectional and Mendelian randomization (MR) analyses to address the unclear role of SUA in bone metabolism.

Methods: Data from the 2015-2020 National Health and Nutrition Examination Survey were analyzed using multiple logistic regression, restricted cubic spline (RCS) modeling, and subgroup analyses. MR was performed using the inverse variance weighted method as the primary approach, complemented by diverse methods and sensitivity analyses.

Results: This study included 6,020 participants, of whom 1635 were diagnosed with OP. Based on the fully adjusted Model IV, individuals in the third (Q3) and fourth (Q4) quartiles exhibited a 38% (OR = 0.622; 95% CI: 0.423-0.915; P = 0.030) and 49% (OR = 0.513; 95% CI: 0.320-0.823; P = 0.015) lower risk of osteoporosis, respectively, relative to those in the lowest quartile (Q1) (Table 2). RCS analysis revealed an L-shaped inverse association (P-overall = 0.011; P-non-linear = 0.803) with a turning point around 5.3 mg/dL. Subgroup analysis suggested that sex, race, diabetes status, and serum cholesterol levels were potential effect modifiers (P-interaction < 0.05). MR analysis further demonstrated a significant causal protective effect of SUA levels on OP (OR = 0.870; 95% CI: 0.776-0.974, P = 0.016).

Conclusion: This study provides new evidence that higher SUA levels are associated with reduced risk of OP, offering potential implications for future preventive strategies. Key Points • Higher serum uric acid levels were independently associated with a lower risk of osteoporosis. • Gender, race, diabetes status, and serum cholesterol levels are factors that affect the negative association between serum uric acid and osteoporosis. • Mendelian randomization analysis supported a causal protective effect of serum uric acid levels on osteoporosis.

Keywords: Causality; Cross-sectional study; Mendelian randomization; NHANES; Osteoporosis; Serum uric acid.