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

Aixian Tian,Lei Chen,Kaiqiang Feng,Jianxiong Ma,Zhaojie Liu,Haobo Jia,Xinlong Ma

doi:10.1186/s13018-019-1100-6

Abstract

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

Highlights

Fracture is a worldwide public health problem because of the increased morbidity, mortality, and financial costs [1]
Data should be adjusted for bone mineral density and clinical risk factors so that the Bone turnover biomarkers (BTMs) are evaluated for their value in fracture risk prediction algorithms
After adjusting for potential confounders such as age, body mass index, mobility score, past fractures, and hip bone mineral density (BMD), s-procollagen type I aminoterminal propeptide (PINP) demonstrated a significant positive association with fracture, which indicated that a 1 standard deviation (SD) increment in Serum PINP (s-PINP) was associated with an increased risk of fracture of 28%

Summary

Introduction

Fracture is a worldwide public health problem because of the increased morbidity, mortality, and financial costs [1]. The ability to predict and prevent fractures is limited. The current approaches for predicting who might fracture are largely based on the measurement of bone mineral density (BMD) and the inclusion in risk calculators of certain clinical risk factors. Such risk calculators include FRAX, QFRACTURE, and the Garvan calculator [2]. BMD indicated osteoporosis only in 30–50% of patients with major fragility fracture [3]. The prognostic value of clinical risk factors alone in FRAX is comparable to that of BMD alone [4]. There is an imperious need of identifying additional fracture risk factors not included in currently available strategies

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Conclusion