Ghio Camille, Gravier-Dumonceau Robinson, Lafforgue Pierre, Giorgi Roch, Pham Thao
Department of Rheumatology, Aix Marseille Univ, APHM, Hôpital Sainte-Marguerite, Marseille, France.
Aix Marseille Univ, APHM, INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, ISSPAM, Hop Timone, BioSTIC, Biostatistique et Technologies de l'Information et de la Communication, Marseille, France.
PLoS One. 2025 May 5;20(5):e0318260. doi: 10.1371/journal.pone.0318260. eCollection 2025.
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.
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]).
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.
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.
我们的目的是确定血清I型胶原C末端肽（sCTX）阈值，以预测接受抗吸收治疗的患者在口腔手术前发生药物相关性颌骨坏死（MRONJ）的最低风险。
截至2023年9月，在MEDLINE、EMBase和Cochrane图书馆进行了系统的文献检索，以查找评估接受口腔手术的抗吸收药物暴露患者sCTX水平的病例对照、前瞻性和回顾性研究。我们使用预先确定的表格提取数据。我们按照PRISMA-DTA指南和描述性分析进行了原始百分位数荟萃分析方法，以确定与最低风险相关的阈值，同时使用DerSimonian和Laird加权的随机效应模型（RStudio软件[v. 4.2.0]）评估第95、97.5和99百分位数的总体结果。
纳入了7项涉及1281例患者的研究。大多数患者（96%）接受骨质疏松症治疗，主要使用口服双膦酸盐（94.5%）。58例患者可获得个体数据。在口腔手术后发生MRONJ的患者总体（n = 113）中，sCTX的第95、97.5和99百分位数分别为338.0 pg/mL [95%CI：190.3；485.7]、401.9 pg/mL [95%CI：191.3；612.6]和458.0 pg/mL [95%CI：190.4；725.6]。在接受口服双膦酸盐治疗骨质疏松症的患者（n = 38）中，sCTX的第95、97.5和99百分位数分别为185.3 pg/mL [95%CI：131.3；239.3]、187.4 pg/mL [95%CI：133.9；240.8]和188.6 pg/mL [95%CI：135.4；241.9]。个体数据分析得出的相同百分位数结果相似，即202.0、257.0和260.0 pg/mL。
这项开创性的荟萃分析通过分析接受抗吸收药物治疗的口腔手术患者的sCTX水平来评估MRONJ风险。在接受口服双膦酸盐治疗骨质疏松症的患者中，sCTX阈值为260 pg/mL与MRONJ发生的极低风险相关，超过第99百分位数。相反，对于接受癌症相关疾病治疗的患者，sCTX水平不能可靠地作为识别这种风险的生物标志物。
