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. <Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="justify" colname="c1" colnum="1" /> <colspec align="justify" colname="c2" colnum="2" /> <tbody> <row> <entry nameend="c2" namest="c1"> 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. </entry> </row> </tbody> </tgroup> </Table>

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

期刊论文
发表日期：

2026年2月14日

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Qi-Pei Liu,
Lei-Xiao Zhang,
Jie-Hua Luo,
Hao-Ze Gao,
Kai Wang

摘要

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.