Effects of pH alteration on the pathogenesis of medication-related osteonecrosis of the jaw

Abstract

Introduction: An acidic environment has been recognized to increase catabolic activities and inhibit osteoblastic deposition, and also exhibited in the pathogenesis of various bone diseases. The aim of the study was to investigate the role of systemic and local pH alteration in the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ). Material and methods: Initially, MRONJ was induced in 54 Sprague-Dawley rats via subcutaneous bisphosphonate injections, once a week for 8 weeks. A week prior to bisphosphonate termination, surgical intervention was performed and rats were divided into 3 groups-alkalotic, acidic and control group, wherein each received NaHCO3, NH4Cl and normal saline, respectively for 8 weeks. Upon sacrifice, blood was sent for arterial blood pH analysis and their mandibles were subjected to histomorphometric and mu CT analyses. ONJ was histologically defined as necrotic bone persisting for eight weeks after surgical intervention. Results: Each intervention exemplified its expected outcome wherein each group exhibited a borderline alkalotic (7.43 +/- 0.05) and acidic state (7.27 +/- 37), respectively (P < 0.05). Acidic group showed a higher occurrence of MRONJ (95%) compared to that of alkalotic group (60%) and control (76.9%). Histomorphometric and microstructural evaluation revealed that acidic group presented deteriorated bone architectures with significantly higher necrotic bone fraction, clusters of empty lacunae, N.Oc/B.Pm and lower B.Ar./T.Ar, BV/TV, Tb.Th (P < 0.05). Alkalotic group showed possible protective effects against ONJ versus acidic group, however these trends were not statistically significant. Conclusions: An acidic milieu aggravated ONJ development in an animal model. Further investigations are needed to elucidate the exact role of acid-base balance in MRONJ pathogenesis and possible benefits of alkali supplementation for the prevention.