Association between biomarkers and medication-related osteonecrosis of the jaws: a systematic review

Abstract Objectives Our aim was to conduct a systematic review (SR) of the literature assessing the role of human biomarkers in the diagnosis or prognostication of medication-related osteonecrosis of the jaws (MRONJ). Study design An electronic search without date or language restriction ​​was carried out in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials , Web of Science, and LILACS until March 2018. In addition, a manual search in the grey literature was conducted. The search process was performed by two independent reviewing authors. Eligibility criteria included randomised and non-random clinical trials, prospective or retrospective cohorts, case controls, and case series evaluating the association between biomarkers and MRONJ. The protocol of this SR was registered in PROSPERO under number CRD42018095886. Results The search and selection process yielded 19 studies (2 case series, 6 case-control studies, 9 prospective cohort studies and 2 retrospective studies) published between 2008 and 2018. Twenty-four biomarkers collected from serum, saliva, and urine were investigated by these studies. Eleven biomarkers were possibly related to MRONJ; however, no consensus is observed in the literature in regard to the sensitivity and clinical effectiveness of these biomarkers. Conclusion While many biomarkers have been associated with MRONJ, the present SR found scarce clinical evidence supporting the use of these biomarkers for the diagnosis and prognosis of MRONJ.