The Association between Bone Turnover Markers and Fracture in People with Diabetes: A Systematic Review and Meta-Analysis

Abstract

Background: The increased fracture risk in persons with diabetes is underestimated by conventional fracture predictors. The aims of this study were to conduct a systematic review and a meta-analysis to compare the levels of bone turnover markers (BTM) in persons with diabetes with and without fractures. Methods: We conducted a systematic literature search. Eligibility criteria were studies investigating BTMs in persons with diabetes with/without fractures. For the meta-analysis, we used the standardised mean difference (SMD) of the markers investigated. Results: We included eight observational studies. Levels of osteocalcin, procollagen type 1 amino terminal propeptide (P1NP), and Insulin-like growth factor-1 (IGF-1) were significantly lower in persons with fracture than in persons 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. Levels of N-terminal cross-linked telopeptide of type 1 collagen (NTX), sclerostin, and bone-specific alkaline phosphatase (BAP) were significantly higher in persons 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. In sensitivity analysis removing one larger study, results were insignificant for osteocalcin, P1NP, NTX, and sclerostin. Conclusions: The results suggest that BTMs may be associated with fracture status in persons with diabetes. Persons with diabetes and fracture have lower levels of formative BTMs and IGF-1, and higher levels of NTX, sclerostin, and BAP compared with no fracture, however, some results were dependent on one larger study.