Prediabetes and osteoporotic fracture risk: A meta-analysis of prospective cohort studies

Background Diabetes confers an increased risk of fracture. However, whether prediabetes is also a risk factor of osteoporotic fracture has not been comprehensively examined. We performed a meta-analysis to evaluate the relationship between prediabetes and osteoporotic fracture risk. Methods This meta-analysis included relevant prospective cohort studies from Medline, Embase, and Web of Science databases. A random-effect model after incorporation of the intra-study heterogeneity was selected to pool the results. Subgroup analyses were applied to evaluate the influences of study characteristics on relationship between prediabetes and osteoporotic fracture risk. Results Eight studies including 33,136 community dwelling adult patients were included, and 7429 (22.4%) patients were prediabetic. Prediabetes was not independently associated with a higher risk of osteoporotic fracture compared with normoglycemia (adjusted risk ratio: 1.03, 95% confidence interval: 0.88-1.21, P = 0.69, I-2 = 42%). Sensitivity limited to the elderly population showed consistent results (RR: 1.10, 95% CI: 0.91-1.24, P = 0.15, I-2 = 0%). Subgroup analysis suggested that prediabetes defined by HbA1c (approximately 5.7%-6.4%) was associated with a higher risk of osteoporotic fracture (RR: 1.24, 95% CI: 1.01-1.53, P = 0.04), but not that defined by impaired fasting glucose or impaired glucose tolerance (P = 0.60). Sex, follow-up duration, and adjustment of bone mineral density did not significantly affect the outcome. Conclusions Current evidence does not support that prediabetes is independently associated with osteoporotic fracture risk. Different definitions of prediabetes may affect the association between prediabetes and osteoporotic fracture risk.