Investigation of Sustained BMP Delivery in the Prevention of Medication-Related Osteonecrosis of the Jaw (MRONJ) in a Rat Model

Macromol Biosci. 2019 Nov;19(11):e1900226. doi: 10.1002/mabi.201900226. Epub 2019 Sep 24.


Medication-related osteonecrosis of the jaw (MRONJ) poses an ongoing challenge for clinicians and researchers. Currently, there is a lack of preventative measures available for at-risk patients undergoing tooth extractions, especially those with prior bisphosphonate treatment due to osteoporosis or bone metastasis diagnoses. Here, these issues are addressed using a preventative tissue engineering strategy against MRONJ development. This study evaluates the efficacy of a poly(ethylene glycol)-heparin hydrogel as a tool for the delivery of arginylglycylaspartic acid (RGD) and recombinant human bone morphogenic protein-2 (rhBMP-2). Three groups of skeletally mature rats each receive two doses of intravenous zoledronic acid prior to surgery and undergo extraction of the right first mandibular molar with gingival closure. Experimental groups either have the sockets left empty, filled with hydrogel minus rhBMP-2, or filled with hydrogel plus rhBMP-2. Eight weeks postoperatively specimens are analyzed using radiological, histological, and scanning electron microscopy (SEM) techniques. µCT analysis shows increased bone formation with hydrogel/rhBMP-2 delivery compared to the empty socket. Hydrogel-treated groups display increased presence of osteocytes and increased osteoclastic action compared to the empty sockets. These results represent the first step toward improved delivery of rhBMP-2 and a potential MRONJ preventative for patients undergoing bisphosphonate treatment.

Keywords: bisphosphonatesm; bone morphogenetic; bone regeneration; hydrogel; medication-related osteonecrosis of the jaw.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / pathology
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / prevention & control*
  • Bone Morphogenetic Protein 2 / administration & dosage
  • Bone Morphogenetic Protein 2 / pharmacokinetics*
  • Cells, Cultured
  • Chemoprevention / methods
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / pharmacokinetics*
  • Disease Models, Animal
  • Drug Liberation*
  • Drug-Related Side Effects and Adverse Reactions / prevention & control
  • Humans
  • Hydrogels / pharmacokinetics
  • Osteocytes / drug effects
  • Osteocytes / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacokinetics
  • Transforming Growth Factor beta / administration & dosage
  • Transforming Growth Factor beta / pharmacokinetics*


  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Delayed-Action Preparations
  • Hydrogels
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2