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

Abstract

Objectives 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 IVor 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. Results 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 osteonecrosisrelated 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. Conclusions 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.

Diagnóstico, tratamento e prevenção da osteonecrose maxilar relacionada a medicamentos

“…Embora MARX; CILLO & ULLOA (2007) tenham afirmado que níveis séricos de CTX inferiores a 150 pg/mL apontam um maior risco de MRONJ, estudos mais recentes indicam que a análise do CTX isoladamente não é capaz de predizer o risco de ocorrência de MRONJ (ENCISO et al, 2016;AWAD et al, 2019;SALGUEIRO et al, 2019), o que pode ser influenciado pelo grande número de variáveis capazes de alterar seus valores (sexo, tabagismo, diabetes, entre outros) (KHOSLA, 2008;FLEISHER et al, 2010;PALAZZOLO, 2010) e baixo nível de evidência dos estudos disponíveis (ENCISO et al, 2016). Ainda assim, esse é um exame complementar capaz de apresentar valores referentes à taxa de remodelamento ósseo que pode ser empregado durante períodos de drug holiday que venham a ser instituídos previamente à realização de procedimentos cirúrgicos (LÓPEZ-JORNET et al, 2010;KOTH et al, 2016).…”

“…Níveis mais baixos desse exame (abaixo de 150 pg/mL) estão associados a menor remodelamento ósseo, e poderiam indicar maior risco de desenvolvimento de MRONJ após intervenções cirúrgicas devido à dificuldade de remodelamento e cicatrização da área operada (LÓPEZ-JORNET et al, 2010;KOTH et al, 2016). No entanto, algumas variáveis afetam os valores do CTX, como a idade, consumo de álcool, tabagismo, ovulação, sexo, corticosteróides, diabetes, exercícios e ritmos circadianos, portanto, a capacidade de predição do risco de MRONJ a partir desse exame é muito questionada pela literatura (KHOSLA, 2008;FLEISHER et al, 2010;PALAZZOLO, 2010;ENCISO et al, 2016;SALGUEIRO et al, 2019).…”

An Approach for the Prevention, Diagnosis, and Treatment of Jaw Osteonecrosis: Report of a Case Associated with Zoledronic Acid

“…Nevertheless, she presented with ONJ. Salgueiro et al also concluded that serum CTX levels alone are unreliable as a predictive or preventive measure [ 18 ].…”

Prevention and treatment of oral adverse effects of antiresorptive medications for osteoporosis – A position paper of the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Stomatology and Oral Pathology (Sobep), and Brazilian Association for Bone Evaluation and Osteometabolism (Abrasso)

“…(33), in a retrospective, uncontrolled study of 30 patients, have proposed that C-terminal telopeptide (CTX) levels measured before dental surgery could predict MRONJ. Since then, many other studies have been carried out to investigate the ability of BTMs to predict the occurrence of MRONJ, with conflicting results (34)(35)(36).…”