Biomarkers to predict the onset of biphosphonate-related osteonecrosis of the jaw: A systematic review

Abstract

BackgroundThe goal of this paper was to identify available biomarkers to predict the onset of biphosphonate-related osteonecrosis of the jaw (BRONJ).Material and MethodsCase-control studies comparing the different concentrations of a series of molecules detected in serum and urine as matrices of BRONJ affected patients vs. non-affected were included. PRISMA guidelines for systematic reviews were used for the present paper. Two reviewers independently screened electronic databases (Medline, Web of science, and The Cochrane Library) and performed hand searches. Risk of bias assessment of selected studies was performed by the Newcastle-Ottawa Scale. This study is registered as PROSPERO CRD42017078149.ResultsFrom a total of 601 identified studies, 7 (4 articles with high methodological quality and 3 with medium) articles were included. They investigate 2623 patients, of whom 91 (3.47%) developed BRONJ. A total of 7 biomarkers were identified and classified into 3 groups: bone turnover, angiogenesis and endocrine markers. Conflicting results were found in relation to most biomarkers.ConclusionsThe present review suggests that no useful markers are currently available to evaluate BRONJ risk. Nevertheless, the present paper indicates that a paradigm shift from bone turnover biomarkers to angiogenesis and endocrine markers could shed light on this search. Key words:Biphosphonate, jaw, osteonecrosis, osteoporosis.

Factors Influencing Severity of Medication-Related Osteonecrosis of the Jaw: A Retrospective Study

“…2 Previous studies also suggest that serum C-terminal cross-linking telopeptide of type I collagen (CTX), serum receptor activator for nuclear factor k B ligand (RANKL) and osteoprotegerin (OPG) levels, and the RANKL/OPG ratio may be associated with the severity of MRONJ, but this remains controversial. 3,4,15,16 In the present study, we retrospectively analyzed the clinical data of MRONJ patients to identify the factors associated with severe disease (stage 3 MRONJ).…”

Stress response in periodontal ligament stem cells may contribute to bisphosphonate‑associated osteonecrosis of the jaw: A gene expression array analysis

“…However, slow-response deGs exhibited enrichment in ossification and cartilage-associated signaling pathways. As reported by aghaloo et al (27) and lorenzo-Pouso et al (28), inflammation and inhibition of bone remodeling have been suggested as putative mechanisms of BronJ. While isolated evidence of resorption-generation imbalance (29), periodontal disease (7) and infection (30) has been discovered in patholog-ical research of BronJ, these hypotheses are treated as being exclusive and require validation (31).…”

Association between periodontitis and medication‐related osteonecrosis of the jaw: A systematic review and meta‐analysis

“…In accordance with the discussed literature, these molecular pathways have been explored in search of therapies or prevention strategies, such as the identification of biomarkers, and to a greater or lesser extent these have not helped with the discovery of conclusive strategies for these emerging matters. Once a landmark initiative, the use of serum CTX with a predictive or prognostic value for MRONJ is still highly debated . In this line, Fleisher et al reported on a cohort of 26 patients receiving BPs with CTX levels <150 pg/mL who underwent surgical management for BRONJ, or simply at‐risk patients who went through surgical interventions and who all exhibited a 100% positive response rate without relapse or complications.…”

“…Once a landmark initiative, the use of serum CTX with a predictive or prognostic value for MRONJ is still highly debated. 6,43 the presence of variants that do not present exposed necrotic bone.…”