BRONJ Review
Temporary Files

Author: Gianpiero Pescarmona
Date: 01/05/2019


MRONJ follows nitrogen-containing bisphosphonates (N-BPs) administration

Metabolic effects of N-BPs :

Effect of N-BPs on Mevalonate Pathway

Underlying Mechanisms and Therapeutic Strategies for Bisphosphonate-Related Osteonecrosis of the Jaw - BRONJ 2017

The inhibition of farnesyl diphosphate synthase (FPP) leads to

  • an increase of uphill substrates (IPP)
  • a decrease of downhill substrates (cholesterol, CoQ10, farnesylPP and related metabolisms)

The decrease of CoQ10 slows the respiratory chain rate leading to:

  • decrease of the intracellular ATP
  • decreased heme synthesis rate
    • decrease of eNOS activity
    • decrease of Cytochrome C (with additional impairment of respiratory chain)

The prevalence of BRONJ in patients under N-BPs is around 10?

Median age is high

Additional Risk Factors

Histological findings

2019-05-01T22:47:03 - Gianpiero Pescarmona

"Epidermal Growth Factor Reverses the Inhibitory Effects of the Bisphosphonate, Zoledronic Acid, on Human Oral Keratinocytes and Human Vascular Endothelial Cells In Vitro via the Epidermal Growth Factor Receptor (EGFR)/Akt/Phosphoinositide 3-Kinase (PI3K) Signaling Pathway. 2019":

Zoledronic acid treatment of HOKs and HUVECs had no significant effects on apoptosis (P>0.05), but significantly reduced expression levels of p-EGFR, p-Akt, p-PI3K, p-mTOR), and p-eNOS (P<0.05); EGF partially reversed these effects and increased the expression levels (P<0.05). CONCLUSIONS EGF partially reversed the effects of the bisphosphonate, zoledronic acid, on HOKs and HUVECs in vitro via the EGFR/Akt/PI3K signaling pathway. Further studies are required to determine the effects of EGF on MRONJ including bisphosphonate-related osteonecrosis of the jaw.

Learning from experience. Proposal of a refined definition and staging system for bisphosphonate‐related osteonecrosis of the jaw (BRONJ) 2012

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