Objective: Our aim was to determine serum C-terminal telopeptide of type I collagen (sCTX) thresholds for predicting the minimal risk of medication-related osteonecrosis of the jaw (MRONJ) in patients undergoing anti-resorptive therapy prior to oral surgery.
Methods: A systematic literature search was conducted in MEDLINE, EMBase, and the Cochrane Library up to September 2023 for case-control, prospective and retrospective studies that assessed sCTX levels in patients exposed to anti-resorptive drugs who underwent oral surgery. We extracted data using a predetermined form. We performed an original percentile meta-analysis method, following PRISMA-DTA guidelines and descriptive analysis to identify the threshold associated with the lowest risk while assessing the overall result of the 95th, 97.5th and 99th percentiles with a random-effect model with weighting by DerSimonian and Laird (RStudio software [v. 4.2.0]).
Results: Seven studies involving 1281 patients were included. Most patients (96%) were treated for osteoporosis, predominantly with oral bisphosphonates (94.5%). Individual data were available for 58 patients. In the entire population of patients who experienced MRONJ after oral surgery (n = 113), the 95th, 97.5th and 99th percentiles of sCTX were 338.0 pg/mL [95%CI: 190,3; 485,7], 401.9 pg/mL [95%CI: 191,3; 612,6], and 458.0 pg/mL [95%CI: 190,4; 725,6], respectively. Among those treated with oral bisphosphonates for osteoporosis (n = 38), the sCTX 95th, 97.5th and 99th percentiles were 185.3 pg/mL [95%CI: 131,3; 239,3] 187.4 pg/mL [95%CI: 133,9; 240,8] and 188.6 pg/mL [95%CI: 135,4; 241,9], respectively. The determination of these same percentiles with individual data analysis yielded similar results, i.e., 202.0, 257.0 and 260.0 pg/mL.
Conclusion: This pioneering meta-analysis assesses the risk of MRONJ by analyzing sCTX levels in patients undergoing oral surgery while exposed to antiresorptive drugs. Among patients receiving oral bisphosphonate therapy for osteoporosis, a sCTX threshold of 260 pg/mL is linked to an extremely low risk of MRONJ occurrence, surpassing the 99th percentile. Conversely, for patients undergoing treatment for cancer-related conditions, sCTX levels do not reliably serve as a biomarker for identifying this risk.
Copyright: © 2025 Ghio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.