The relationship between subclinical thyroid dysfunction and the risk of fracture or low bone mineral density: a systematic review and meta-analysis of cohort studies.

Our aim was to assess the risk of fractures or low bone mineral density (BMD) associated with subclinical thyroid dysfunction among cohorts. We systematically searched Medline (via PubMed), EMBASE, Cochrane Library, Web of Science, CENTRAL and SinoMed up to 31 July 2016 to identify cohort studies which have analyzed associations between subclinical thyroid dysfunction and fracture or BMD. A total of 19 population-based cohorts including 79,368 participants with relationships between subclinical thyroid dysfunction and fractures or BMD were identified as eligible for this meta-analysis. Subclinical hypothyroidism was associated with relative risks (RRs) of 1.34 (95% confidence interval [CI] 1.14, 1.58; I 2  = 32%) for hip fracture, 1.27 (95% CI 1.02, 1.58; I 2  = 51.9%) for any location of fracture, and 1.25 (95% CI 1.04, 1.50) for forearm fracture. Subclinical hyperthyroidism was associated with RRs of 1.71 (95% CI 1.06, 2.76; I 2  = 0.0%) for spine fracture, 1.20 (95% CI 1.03, 1.39; I 2  = 0.0%) for non-spine fracture, 1.44 (95% CI 1.21, 1.71; I 2  = 0.0%) for hip fracture, and 1.38 (95% CI 1.21, 1.58; I 2  = 0.0%) for any location of fracture. Subgroup analysis was conducted according to whether thyroid/anti-thyroid drug users were excluded or not and the results were similar. The change in BMD at the hip (weighted mean difference [WMD] = -0.060, 95% CI -0.116, -0.004; I 2  = 0.0%) and femoral neck (WMD = -0.046, 95% CI -0.077, -0.015; I 2  = 0.0%) was significantly decreased in the subclinical hyperthyroidism group compared with the euthyroidism groups in females. We failed to find any associations between the change in BMD and subclinical hypothyroidism. The overall quality of evidence was low in all outcomes. Subclinical hyperthyroidism and subclinical hypothyroidism were associated with an increased risk of fractures. Although subclinical hyperthyroidism was related to reduced BMD, no evidence could prove a definite association between subclinical hypothyroidism and the risk of low BMD.