EPMA Journal

, Volume 10, Issue 1, pp 21–29 | Cite as

Value of pre-operative CTX serum levels in the prediction of medication-related osteonecrosis of the jaw (MRONJ): a retrospective clinical study

  • Martin Salgueiro
  • Michael Stribos
  • Li Fang Zhang
  • Mark Stevens
  • Mohamed E. Awad
  • Mohammed ElsalantyEmail author



The low incidence yet severe presentation of medication-related osteonecrosis of the jaw (MRONJ) makes it necessary to develop reliable predictive and preventive strategies. This study explored the value of pre-operative carboxy-terminal collagen crosslinks (CTX) serum level in the prediction of osteonecrosis-related complications in patients on bisphosphonate therapy.

Patients and methods

We examined patient records over 4 years (a total of 137 patients). Biometric data were extracted, in addition to type of treatment, CTX levels, drug holiday, procedure, complications, and co-morbidities. Non-parametric Wilcoxon two-sample tests were used to test the effect of initial CTX level in IV or PO and whether it was predictive of complications. Two independent proportion tests were used for testing the two different complication incident rates before or after the drug holiday.


A total of 93 patients were included in the study, of whom 88.17% were female. A total of 11 patients were receiving IV bisphosphonates at the time of initial presentation, 82 oral bisphosphonates. Out of 64 patients who underwent invasive dental procedure (IDP) before a drug holiday, eight were on IV bisphosphonates. Three patients in this group experienced osteonecrosis-related complications (37.5%). Out of the remaining 56 patients on oral bisphosphonates, four (7.14%) developed complications, significantly lower than the IV bisphosphonate group (p = 0.0364). On the other hand, of the 34 patients placed on a drug holiday prior to IDP, only one subject developed complications related to osteonecrosis. Five subjects who had operations both before and after drug holiday did not experience any complications. No statistical difference was detected in complication rates based on initial CTX level (above versus below 150 pg/ml), gender, comorbidities, or total duration of bisphosphonate treatment (p = 0.2675). The sensitivity and specificity of CTX cutoff of 150 pg/ml in predicting osteonecrosis were 37.5% and 57.7, respectively.


Serum levels of CTX by itself are not reliable as a predictive or preventive measure for such complications. Our data also suggested that a drug holiday of 5 months was not helpful in preventing osteonecrosis-related complications in patients on intravenous bisphosphonates. Further studies are urgently needed to develop adequate predictive and preventive strategies of MRONJ.


Bisphosphonates Osteonecrosis Drug holiday Osteoporosis treatment Prediction of complications 


Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests.

Consent for publication

Not applicable.

Ethical approval

All investigations conformed to the principles outlined in the Declaration of Helsinki and were performed with approval by the Institutional Review Board (IRB) at Augusta University (Pro00001995; 5/3/2014).


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Copyright information

© European Association for Predictive, Preventive and Personalised Medicine (EPMA) 2019

Authors and Affiliations

  1. 1.Oral and Maxillofacial Surgery Department, Dental College of GeorgiaAugusta UniversityAugustaUSA
  2. 2.Medical Student, Medical College of GeorgiaAugusta UniversityAugustaUSA
  3. 3.Department of Biostatistics and Epidemiology, Medical College of GeorgiaAugusta UniversityAugustaUSA
  4. 4.Department of Oral Biology and Diagnostic Sciences, Dental College of GeorgiaAugusta UniversityAugustaUSA
  5. 5.Department of Oral Biology, Dental College of DentistryAugusta UniversityAugustaUSA

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