Previous studies suggested possible bone loss and fracture risk in patients with systemic lupus erythematosus (SLE). The aim of this systematic review and meta-analysis was to assess the strength of the relationship of SLE with fracture risk and the mean difference of bone mineral density (BMD) levels between SLE patients and controls. Literature search was undertaken in multiple indexing databases on September 26, 2015. Studies on the relationship of SLE with fracture risk and the mean difference of BMD levels between SLE patients and controls were included. Data were combined using standard methods of meta-analysis. Twenty-one studies were finally included into the meta-analysis, including 15 studies on the mean difference of BMD levels between SLE patients and controls, and 6 studies were on fracture risk associated with SLE. The meta-analysis showed that SLE patients had significantly lower BMD levels than controls in the whole body (weighted mean difference [WMD] = -0.04; 95 % CI -0.06 to -0.02; P < 0.001), femoral neck (WMD = -0.06; 95 % CI -0.07 to -0.04; P < 0.001), lumbar spine (WMD = -0.06; 95 % CI -0.09 to -0.03; P < 0.001), and total hip (WMD = -0.05; 95 % CI -0.06 to -0.03; P < 0.001). In addition, the meta-analysis also showed that SLE was significantly associated with increased fracture risk of all sites (relative risk [RR] = 1.97, 95 % CI 1.20-3.25; P = 0.008). Subgroup analysis by adjustment showed that SLE was significantly associated with increased fracture risk of all sites before and after adjusting for confounding factors (unadjusted RR = 2.07, 95 % CI 1.46-2.94, P < 0.001; adjusted RR = 1.22, 95 % CI 1.05-1.42, P = 0.01). Subgroup analysis by types of fracture showed that SLE was significantly associated with increased risks of hip fracture (RR = 1.99, 95 % CI 1.55-2.57; P < 0.001), osteoporotic fracture (RR = 1.36, 95 % CI 1.21-1.53; P < 0.001), and vertebral fracture (RR = 2.97, 95 % CI 1.71-5.16; P < 0.001). This systematic review and meta-analysis provides strong evidence for the relationship of SLE with bone loss and fracture risk.

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