Hyperuricemia protects against low bone mineral density, osteoporosis and fractures: a systematic review and meta‐analysis

Abstract Background Serum uric acid ( SUA ) accounts for about 50% of extracellular antioxidant activity, suggesting that hyperuricemia may have a protective role in diseases characterized by high levels of oxidative stress, such as osteoporosis. We aimed to meta‐analyse data regarding bone mineral density ( BMD ), osteoporosis and fractures in people with higher SUA vs. lower SUA concentrations. Materials and methods Two investigators conducted a literature search using PubMed and Scopus, without language restrictions. Standardized mean differences ( SMD s) and 95% confidence intervals ( CI s) were used for BMD ; risk ratios ( RR s) and adjusted odds ratios ( OR s) for cross‐sectional data. Most possible adjusted hazard ratios ( HR s) were used to assess the association between baseline SUA and incident fractures. Results Of 1405 initial hits, 19 studies were eligible including a total of 55 859 participants. Subjects with higher SUA levels had significantly higher BMD values for the spine (six studies; SMD = 0·29; 95% CI : 0·22–0·35; I 2 = 47%), total hip (seven studies; SMD = 0·29; 95% CI : 0·24–0·34; I 2 = 33%) and femoral neck (six studies; SMD = 0·25; 95% CI : 0·16–0·34; I 2 = 71%). Simple correlation analyses substantially confirmed these findings. An increase of one standard deviation in SUA levels reduced the number of new fractures at follow‐up (three studies; HR = 0·83; 95% CI : 0·74–0·92; I 2 = 0%). No significant differences between men and women emerged, although data about women were limited. Conclusions Hyperuricemia was found independently associated with BMD and fractures, supporting a protective role for uric acid in bone metabolism disorders.