The Association Between Serum Uric Acid Level and the Risk of Fractures: a Systematic Review and Meta-analysis

Controversy has arisen in regarding the association between serum uric acid (UA) and fracture risk. Therefore, we conducted a systemic review and meta-analysis by pooling estimate of five prospective studies (29,110 participants). Results showed that an increased serum UA level is associated with a lower risk of fracture. Numerous studies have demonstrated that high serum UA is a relevant risk factor for a wide variety of diseases, whereas new understanding in serum uric acid follows recent reports demonstrating a protective role of UA in health status. However, the association between serum UA and fracture remains controversial. Therefore, we conduct a systemic review and meta-analysis to determine whether elevated UA level is a protective factor for fracture among prospective studies. We searched for studies published before May 6, 2016, using PubMed, Embase, and Cochrane databases, without any language restriction. The inclusion criteria were published studies investigating the association between UA and fractures. Two authors independently screened the retrieved articles in accordance to the predefined inclusion criteria. We pooled the study-specific relative risk estimates using a random-effect model for comparison of persons whose UA levels were in the top tertile with those in the bottom tertile. Factors that may predict these associations were evaluated in subgroup analysis and meta-regression. The five included prospective studies included 29,110 participants. In random-effect models that included all five included studies, the summary hazard ratios (HRs) (top vs bottom tertiles) were 079 (95% CI, 0.69 to 0.89), without evidence of heterogeneity (P for heterogeneity = 0.458; I  = 0%). Similar results were shown when pooling estimate of three higher-quality studies (HR 0.80 95% CI, 0.69 to 0.93). The association between UA and fracture remained in sensitivity and subgroup analyses. An increased serum UA level is shown to be associated with a lower risk of fracture, albeit additional large, high-quality prospective studies or a meta-analysis of individual data are still needed to verify the association.