Background/Purpose: Normal mineral metabolism is critical for skeletal integrity.  Uric acid (UA) is produced from purines by the enzyme xanthine oxidase, and elevated levels may cause gouty arthritis and kidney stones. High uric acid levels result in endothelial damage and play a role in disease processes including hypertension, heart failure and renal disease.  Conversely, UA also appears to function as an anti-oxidant and may protect against the oxidative stress associated with aging and disease.  Recently, serum uric acid was reported associated with elevated bone mineral density and lower prevalence of fractures in older men (Nabipour, JBMR 2011).  To confirm this association, we performed a prospective case-cohort study to understand the relation of uric acid and fracture risk in older men enrolled in the Osteoporotic Fractures in Men (MrOS) study.

Methods:  In the cohort of 5994 men 65 and older attending the baseline MrOS examination, we evaluated a subgroup 1,682 men in a case-cohort study design. This group included 387 men with incident non-vertebral fractures (with 73 hip fractures) and a sample of 1385 men randomly selected from the cohort with baseline mineral and calcium hormone measurements.  Serum uric acid was measured in baseline serum samples by Unical DxC 800 auto-analyser (Beckman Coulter, Fullerton, CA, USA).  All men who experienced any non-vertebral fracture from baseline until February 2007 (average follow-up 4.7 years) were included in the analysis.  Incident fractures were confirmed with x-ray reports.  Hip bone mineral density was obtained at the baseline.   Modified proportional hazards models that account for case-cohort study design were used to estimate the relative hazards (RH) of fracture in men for serum uric acid.

Results: Subjects with incident non-vertebral fractures were older, had lower total hip BMD, and higher serum phosphorus. Cases were more likely to report a history of falls and to be frail (all p<0.01).  Overall, there was no difference in risk of hip fracture by baseline uric acid after adjustment for age, clinic site, BMI, race, total hip BMD, vitamin D and PTH.   However, there is 19% decrease risk of non-vertebral fractures (95% CI 0.71-0.93; p=0.003) per 1 SD increase of baseline UA after multivariate adjustment.  Total hip BMD was significantly higher in the group of men with high uric acid levels and increased continuously across quartiles of uric acid after multivariate adjustment (p for trend=0.009).

Conclusion: Higher serum uric acid levels were associated with a reduction in risk of incident fractures and higher hip bone mineral density.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-serum-uric-acid-and-incident-fractures-in-elderly-men/