Reference markers of bone turnover for prediction of fracture: a meta-analysis

ObjectiveTo explore whether bone turnover biomarkers (BTMs), i.e., C-terminal telopeptide of type I collagen (CTX) and procollagen type I aminoterminal propeptide (PINP), are associated with fracture.MethodsWe searched electronic database including PubMed, Embase and Cochrane Library, and the reference lists of relevant articles published from inception to August 22, 2018. An updated meta-analysis was performed to assess the prediction value of CTX and PINP in fracture.ResultsNine articles met our inclusion criteria and were included in the meta-analysis. The crude and adjusted effect size between PINP and fracture were extracted from two and five studies, respectively. PINP was not associated with fracture incidence without adjusting covariates (crude GR, 1.03; 95% CI, 0.91-1.17). After adjusting for potential confounders, PINP demonstrated a significant positive association with fracture (adjusted GR, 1.28; 95% CI, 1.15-1.42). In the subgroup analysis of studies after adjusting covariates, there were significant associations in women. Both the crude (1.16, 95%CI, 1.04-1.20) and adjusted GR (1.20, 95%CI, 1.05-1.37) shown positive relationships between CTX and fracture, which were extracted from four and six studies, separately. The sensitivity analysis confirmed the stability of the results. In the subgroup analysis of studies after adjusting covariates, there were significant associations in the subgroups of elderly, female, and hip fracture patients.ConclusionsOur results indicate a statistically significant but modest association between BTMs (s-PINP or s-CTX) and future fracture risk after adjusting for BMD and clinical risk factors. The causal relationship between the two clinical conditions requires future validation with more standardized studies.Registration numberCRD42018107879