Assessing the utility of serum C-telopeptide cross-link of type 1 collagen as a predictor of bisphosphonate-related osteonecrosis of the jaw: A systematic review and meta-analysis

Abstract

Background: The authors of this systematic review and meta-analysis assessed the utility of serum C-telopeptide cross-link of type 1 collagen (sCTX), a biomarker of bone resorption, as a predictor of the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ).

Types of studies reviewed: The authors searched for studies involving adult participants, written in English, and published through January 20, 2016, using the following electronic databases: the Cochrane Library, MEDLINE via PubMed, and Web of Science. They also searched Google Scholar and the reference lists of all eligible trials and reviews. They identified 16 articles that met their inclusion criteria (9 controlled studies and 7 case series). They applied the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews and meta-analyses. They independently extracted data in duplicate, including the characteristics of study participants, risk factors, control groups, and outcomes. They assessed risk of bias, and they resolved any disagreements between review authors through discussion.

Results: A meta-analysis with 9 controlled studies revealed no significant difference in mean sCTX values between patients with BRONJ and control participants (difference in means, -31.417; 95% confidence interval [CI], -91.560 to 28.726; P = .306). A second meta-analysis with 4 studies showed no significant difference in risk of having an sCTX value below 150 picograms per milliliter for patients with BRONJ compared with control participants (risk ratio, 1.892; 95% CI, 0.636-5.626; P = .251).

Conclusions and practical implications: A systematic review of the literature with meta-analysis does not support the use of sCTX levels as a predictor of the development of BRONJ. Further prospective large sample studies are needed to understand the role of sCTX as a predictor for BRONJ.

Keywords: BP; BRONJ; Bisphosphonate; CTX; MRONJ; aminobisphosphonate; bisphosphonate-related osteonecrosis of the jaw; nitrogen-containing bisphosphonate.