George Feldman, PhD, DMD
Thomas Jefferson University
Testing a Novel Treatment for MRONJ in a Rat Model
As a dentist-scientist whose career has interwoven the molecular biology of bone and cartilage with clinical practice, Dr. George Feldman finds the challenge of developing a new more effective treatment for Medically Related Osteonecrosis of the Jaw especially exciting.
Abstract:
MRONJ is palliative, occasionally a “drug holiday” is prescribed. This treatment of signs of the disorder does not address its cause and, in the case of NBP cessation, often leads to mandibular fractures. There is no current cause-based treatment to speed healing and reduce morbidity. Most MRONJ is caused by nitrogen containing bisphosphonates that directly block a metabolic pathway that is crucial for osteoclast and osteoblast function. NBPs are known to accumulate in bone and to be toxic to gingival fibroblasts and keratinocytes and osteoclasts. We hypothesize that geranyl-geraniol, a metabolite downstream of this block will restore cell function. It has been shown that by supplying this metabolite these cell types can be rescued from the toxic effects of NBPs in vitro. We propose here to show that MRONJ produced in a proven rat model can be locally reversed by using GGOH incorporated into a bioconductive calcium phosphate carrier. If successful this metabolite could be developed into the first treatment for MRONJ based on its etiology.
Publications:
JAGGED1 stimulates cranial neural crest cell osteoblast commitment pathways and bone regeneration independent of canonical NOTCH signaling Archana Kamalakar 1, Jay M McKinney 2, Daniel Salinas Duron 3, Angelica M Amanso 4, Samir A Ballestas 5, Hicham Drissi 6, Nick J Willett 7, Pallavi Bhattaram 8, Andrés J García 9, Levi B Wood 10, Steven L Goudy 11 PMID: 32980561. DOI: 10.1016/j.bone.2020.115657.
Yagnik A, Feldman G, et al. Development of a Cause-Based Treatment for Nitrogen Containing Bisphosphonate Induced MRONJ Journal of Oral and Maxillofacial Surgery (2019) Volume 77, Issue 9, e44 – e45
Young D, Diecidue R, Taub D, Feldman G Development of a Cause-based Treatment for NBP-induced MRONJ Journal of Oral and Maxillofacial Surgery(2021)Volume 79, Issue 10, 2021, e51-e52,ISSN 0278-2391
FeldmanG, Young D, Freeman T, Taub D, Diecidue R Developing a Cause-based Treatement for MRONJ Heliyon submitted 11/2022.