A Review Into the Effects of Pamidronic Acid and Zoledronic Acid on the Oral Mucosa in Medication-Related Osteonecrosis of the Jaw

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is a growing problem without an effective treatment, presenting as necrotic bone sections exposed via lesions in the overlying soft tissue. There is currently a lack of clarity on how the factors involved in MRONJ development and progression contribute to disease prognosis and outcomes. Bisphosphonates (BPs), the most common cause of MRONJ, affect bone remodeling, angiogenesis, infection, inflammation and soft tissue toxicity, all of which contribute to MRONJ development. This article reviews the cellular mechanisms through which BPs contribute to MRONJ pathology, with a focus on the effects on cells of the oral mucosa. BPs have been shown to reduce cell viability, reduce proliferation, and increase apoptosis in oral keratinocytes and fibroblasts. BPs have also been demonstrated to reduce epithelial thickness and prevent epithelial formation in three-dimensional tissue engineered models of the oral mucosa. This combination of factors demonstrates how BPs lead to the reduced wound healing seen in MRONJ and begins to uncover the mechanisms through which these effects occur. The evidence presented here supports identification of targets which can be used to develop novel treatment strategies to promote soft tissue wound healing and restore mucosal coverage of exposed bone in MRONJ.

Medication‐related osteonecrosis of the jaw: Case series and literature review

“…Approximately 75% of MRONJ cases affect the mandible 1 . The mandible has a thinner mucosa compared to the maxilla which predisposes it to damage 16 . In addition, the mandible has a singular main blood supply hence prone to avascular necrosis 6 .…”

“…1 The mandible has a thinner mucosa compared to the maxilla which predisposes it to damage. 16 In addition, the mandible has a singular main blood supply hence prone to avascular necrosis. 6 The most common precipitating factor for necrosis is tooth extraction.…”

Antiresorptive agents enhance ossification of free flap reconstructions of the mandible: a radiological retrospective cohort study

“…Bisphosphonates not only affect bone metabolism but also have been shown to reduce cell viability, reduce proliferation, and increase apoptosis in oral keratinocytes and fibroblasts. Moreover, bisphosphonates have been demonstrated to reduce epithelial thickness and prevent epithelial formation in three-dimensional tissue-engineered models of the oral mucosa ( 32 ).…”

MicroRNA in medication related osteonecrosis of the jaw: a review

“…BPs have been shown to be toxic to both oral keratinocytes and fibroblasts, and negatively affect cell cell viability, apoptosis, proliferation and migration ( Landesberg et al, 2008 ; Kobayashi et al, 2010 ; Cozin et al, 2011 ; Bullock et al, 2022 ). During cell proliferation which is crucial wound healing and restoration of the mucosal barrier, keratinocytes were prevented from completing their cell cycles while fibroblasts became apoptotic when treated with BPs ( Bullock et al, 2022 ). In addition, disrupted transforming growth factor beta 1 (TGFβ1) signaling was discovered with delayed periodontal repair in BRONJ human biopsy tissue ( Wehrhan et al, 2011 ).…”