The Association between Bone Turnover Markers and Fracture in People with Diabetes: A Systematic Review and Meta-Analysis
The increased risk of fractures in individuals with diabetes has been underestimated by conventional fracture predictors such as the bone mineral density Tscore or the Fracture Risk Assessment Tool. The present study conducted a systematic review and a meta-analysis to investigate the association between the levels of bone turnover markers (BTMs) and fractures in patients with diabetes. Methods: We conducted a systematic literature search. Eligibility criteria were studies investigating BTMs in
... vestigating BTMs in patients with diabetes with/without fractures. For the meta-analysis, we primarily used the fixed effects model. The estimates were reported as the standardized mean difference (SMD). Results: We included eight observational studies. The levels of osteocalcin, procollagen type 1 amino terminal propeptide (P1NP), and insulin-like growth factor-1 (IGF-1) were found to be significantly lower in individuals with fracture than in those without fracture (-0.36 [-0.46, -0.26]) (SMD [95% confidence interval], (-0.57 [-0.75, -0.40]), and (-0.50 [-0.61, -0.39]), respectively. The levels of N-terminal cross-linked telopeptide of type 1 collagen (NTX), sclerostin, and bone-specific alkaline phosphatase (BAP) were significantly higher in patients with fracture (0.24 [0.13, 0.35], (0.47 [0.29, 0.65]), and (0.14 [0.01, 0.27]) , respectively, whereas C-terminal cross-linked telopeptide (CTX) showed no difference between the groups. The sensitivity analysis revealed an effect of study size but not study design. Conclusions: The results suggest that BTMs could be associated with fracture status in individuals with diabetes with lower levels of formative BTMs and IGF-1 and higher levels of NTX, sclerostin, and BAP in these individuals than in those without fracture. However, some results depended on one large study.