title: High C-Terminal Cross-Linking Telopeptide Levels Are Associated With a Minimal Risk of Osteonecrosis of the Jaws in Patients Taking Oral Bisphosphonates and Having Exodontia.
abstract: OBJECTIVE
  The clinical significance of bone turnover marker C-terminal cross-linking telopeptide (CTX) levels less than 150 pg/mL among recipients of oral bisphosphonate (OBP) medications who develop osteonecrosis of the jaws (MRONJ) after exodontia is unclear. We searched the published data to determine the prevalence of such levels and the association, if any, with development of MRONJ.
  
  
  METHODS
  A systematic review of published studies in the PubMed database was undertaken to ascertain the prevalence of preoperative, fasting CTX levels less than 150 pg/mL among recipients of OBP scheduled for exodontia and to determine whether such levels are associated with the development of postoperative MRONJ. The data were aggregated and analyzed to provide the sensitivity, specificity, and positive and negative predictive values of the association between low CTX levels and the development of MRONJ.
  
  
  RESULTS
  Two studies were chosen for review. The first, with an enrollment of 21 patients, reported that 10 (48%) patients had a preoperative CTX level less than 150 pg/mL and that after exodontia, none developed MRONJ. The second study, with an enrollment of 950 patients, reported that approximately 282 (30%) had a preoperative CTX level less than 150 pg/mL. All the patients with depressed CTX levels were offered a "drug holiday"; however, only 101 accepted the offer. Of the remaining 181 patients, 4 developed MRONJ. The aggregated study data have demonstrated that 30% of patients evidence CTX levels less than 150 pg/mL and that the sensitivity and specificity of these levels in association with the development of MRONJ was 100% and 80.7%, respectively. The positive predictive value was 2.09% and the negative predictive value was 100%.
  
  
  CONCLUSIONS
  The published data suggest that approximately one third of patients exposed to OBP will evidence depressed CTX levels and that only a very small minority (∼2%) will develop postexodontia MRONJ. Prudence would suggest that patients scheduled for exodontia and receiving OBPs should be informed about the strengths and weaknesses of the CTX test and that it should be offered during the consent process.
authors: Associate Chief of Staff and Director of Graduate Medical Education, Veterans Affairs Greater Los Angeles Healthcare System; Director of Quality Assurance, Hospital Dental Service, Ronald Reagan University of California, Los Angeles, Medical Center; and Professor-in-Residence, Department of Oral and Maxillofacial Surgery, University of California, Los Angeles, School of Dentistry, Los Angeles, CA. Electronic address: arthur.friedlander@va.gov.
authors: Arthur H
authors: AH
authors: Friedlander
authors: Director of the Research Fellowship and Inpatient Oral and Maxillofacial Surgery, Veterans Affairs Greater Los Angeles Healthcare System; Instructor, Department of Oral and Maxillofacial Surgery, University of California, Los Angeles, School of Dentistry, Los Angeles, CA.
authors: Tina I
authors: TI
authors: Chang
authors: Research Fellow, Oral and Maxillofacial Surgery Section, Dental Service, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA.
authors: Renna C
authors: RC
authors: Hazboun
authors: Associate Dean for Education and Professor of Advanced Prosthodontics, Weintraub Center for Reconstructive Biotechnology, University of California, Los Angeles, School of Dentistry, Los Angeles, CA.
authors: Neal R
authors: NR
authors: Garrett
mesh_terms: D000284:Administration, Oral; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000150:complications / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism*; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D010455:Peptides / Q000378:metabolism*; D014081:Tooth Extraction / Q000009:adverse effects*
chemical_list: D024042:Collagen Type I; D004164:Diphosphonates; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide