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). 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. ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T3 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.

Combined Administration of Bisphosphonates, Chemotherapeutic Agents, and/or Targeted Drugs Increases the Risk for Stage 3 Medication-Related Osteonecrosis of the Jaw: A 4-Year Retrospective Study

“…Whether serological biomarkers can be used for the diagnosis and prognosis of MRONJ is still controversial [ 33 ]. CTX, PINP, osteocalcin, calcitonin, PTH, 25-hydroxy vitamin D, Ca, Mg, P, and BAP are considered to be associated with bone metabolism.…”

Weak evidence for the management of medication‐related osteonecrosis of the jaw: An overview of systematic reviews and meta‐analyses

“…However, there is no evidence that advanced stages of MRONJ (I, II, and III) respond biologically to different proposed therapies. In addition, there is also no evidence of the prognosis and recurrence of treated lesions 31 . The low number of RCTs analyzing treatments for MRONJ contributes to the diversity of the proposed protocols.…”

Comparison of the Effect of Oral Versus Intravenous Bisphosphonate Administration on Osteoclastogenesis in Advanced-Stage Medication-Related Osteonecrosis of the Jaw Patients

“…Medication-related osteonecrosis of the jaw (MRONJ) has emerged as a devastating side effect induced secondary to long-term administration of antiresorptive medications since its first description in 2003 [1][2][3][4]. It is characterized by the features of an open alveolar socket, exposed necrotic bone or sequestra, increased expression of inflammatory infiltrates, osseous sclerosis, and radiologic signs of osteolysis [5].…”

“…The pathogenesis of MRONJ is not currently correlated with one specific etiological mechanism [1,4], but it is speculated that the inhibitory pharmacological effect on osteoclasts by antiresorptive drugs such as bisphosphonates (BP) and denosumab plays a central role [4,10,11]. Bisphosphonates represent a major class of antiresorptive medications prescribed for the treatment and prevention of osteoporosis, multiple myeloma, and skeletal related events (SREs) of malignant solid tumors [1,12].…”

“…The pathogenesis of MRONJ is not currently correlated with one specific etiological mechanism [1,4], but it is speculated that the inhibitory pharmacological effect on osteoclasts by antiresorptive drugs such as bisphosphonates (BP) and denosumab plays a central role [4,10,11]. Bisphosphonates represent a major class of antiresorptive medications prescribed for the treatment and prevention of osteoporosis, multiple myeloma, and skeletal related events (SREs) of malignant solid tumors [1,12]. It lowers bone turnover following oral surgery via the inhibition of osteoclast-mediated bone resorption, which occurs through the disruption of the mechanisms crucial for the formation, proliferation, and resorption capability of osteoclasts [2,4,11,[13][14][15][16].…”