J Korean Assoc Oral Maxillofac Surg.  2020 Jun;46(3):191-196. 10.5125/jkaoms.2020.46.3.191.

Regenerative effect of recombinant human bone morphogenetic protein-2/absorbable collagen sponge (rhBMP-2/ACS) after sequestrectomy of medication-related osteonecrosis of the jaw (MRONJ)

• Min SH
• Kang NE
• Song SI
• Lee JK

• KMID: 2504305
• DOI: http://doi.org/10.5125/jkaoms.2020.46.3.191

Abstract

Objectives
Beyond the original application approved by the U.S. Food and Drug Administration, recombinant human bone morphogenetic protein- 2 (rhBMP-2) is used for medication-related osteonecrosis of the jaw (MRONJ) treatment because of its bone remodeling enhancement properties. The purpose of the study was to investigate the bone formation effect of rhBMP-2/absorbable collagen sponge (ACS) in patients with MRONJ.
Materials and Methods
In this retrospective cohort study, 26 female patients diagnosed with MRONJ and who underwent mandibular sequestrectomy at Ajou University Dental Hospital from 2010 to 2018 were included. The experimental group was composed of 18 patients who received rhBMP-2/ACS after sequestrectomy, while the control group was composed of 8 patients who did not receive rhBMP-2/ACS after sequestrectomy. A total dose of 0.5 mg of rhBMP-2 was used in the experimental group at a concentration of 0.5 mg/mL. Follow-up panoramic X-rays were taken immediately after the surgery and more than 6 months after the surgery. Using those X-rays, a radiographic index of bone defect area was calculated using the modified Ihan Hren method, which measures radiographic density of the normal bone and the defect site.
Results
This study suggests that rhBMP-2 contributes to new bone formation. The mean radiographic index immediately after surgery and more than 6 months after the surgery for the experimental group was 68.4% and 79.8%, respectively. The mean radiographic index immediately after surgery and more than 6 months after the surgery for the control group was 73.4% and 76.7%, respectively (Wilcoxon signed rank test, P>0.05). The mean radiographic index increased 11.4% in the experimental group and 3.27% in the control group (Mann–Whitney U-test, P <0.05).
Conclusion
Based on the results, use of rhBMP-2/ACS on bone defect sites after sequestrectomy could be a successful strategy for treatment of MRONJ patients.

Keyword

Recombinant human bone morphogenetic protein-2; Osteomyelitis; Bisphosphonate-associated osteonecrosis of the jaw; Osteonecrosis

Figure

• 

  Fig. 1 Surgical procedure of experimental group. Absorbable collagen sponge with absrobed recombinant human bone morphogenetic protein-2 was applied to the bone defect.

• 

  Fig. 2 Bone density analysis method. To measure the radiographic density of the normal bone, the mean value was calculated by measuring each of the three random site around the bone defect area. To measure changes in radiographic density of the bone defect, the bone defect area of the panoramic X-ray was set to the same extent as the panoramic X-ray immediately after surgery, and after six months of surgery. A. Immediately after surgery. B. Postoperation over six months of surgery.

Reference

References

1. Lee JK, Kim KW, Choi JY, Moon SY, Kim SG, Kim CH, et al. 2013; Bisphosphonates-related osteonecrosis of the jaw in Korea: a preliminary report. J Korean Assoc Oral Maxillofac Surg. 39:9–13. DOI: 10.5125/jkaoms.2013.39.1.9. PMID: 24471011. PMCID: PMC3858159.

2. Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, et al. 2014; American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update. J Oral Maxillofac Surg. 72:1938–56. DOI: 10.1016/j.joms.2014.04.031. PMID: 25234529.

3. Gómez Font R, Martínez García ML, Olmos Martínez JM. 2008; Osteochemonecrosis of the jaws due to bisphosphonate treatments. Update. Med Oral Patol Oral Cir Bucal. 13:E318–24.

4. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B. 2009; American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaw - 2009 update. Aust Endod J. 35:119–30. DOI: 10.1111/j.1747-4477.2009.00213.x. PMID: 19961450.

5. Vescovi P, Merigo E, Meleti M, Manfredi M, Fornaini C, Nammour S, et al. 2014; Conservative surgical management of stage I bisphosphonate-related osteonecrosis of the jaw. Int J Dent. 2014:107690. DOI: 10.1155/2014/107690. PMID: 24648841. PMCID: PMC3933473.

6. Cicciù M, Herford AS, Juodžbalys G, Stoffella E. 2012; Recombinant human bone morphogenetic protein type 2 application for a possible treatment of bisphosphonates-related osteonecrosis of the jaw. J Craniofac Surg. 23:784–8. DOI: 10.1097/SCS.0b013e31824dbdd4. PMID: 22565901.

7. Bagan J, Scully C, Sabater V, Jimenez Y. 2009; Osteonecrosis of the jaws in patients treated with intravenous bisphosphonates (BRONJ): a concise update. Oral Oncol. 45:551–4. DOI: 10.1016/j.oraloncology.2009.01.002. PMID: 19251474.

8. Park JH, Kim JW, Kim SJ. 2017; Does the addition of bone morphogenetic protein 2 to platelet-rich fibrin improve healing after treatment for medication-related osteonecrosis of the jaw? J Oral Maxillofac Surg. 75:1176–84. DOI: 10.1016/j.joms.2016.12.005. PMID: 28042979.

9. Freitas RM, Spin-Neto R, Marcantonio Junior E, Pereira LA, Wikesjö UM, Susin C. 2015; Alveolar ridge and maxillary sinus augmentation using rhBMP-2: a systematic review. Clin Implant Dent Relat Res. 17(Suppl 1):e192–201. DOI: 10.1111/cid.12156. PMID: 24102703.

10. Carter TG, Brar PS, Tolas A, Beirne OR. 2008; Off-label use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for reconstruction of mandibular bone defects in humans. J Oral Maxillofac Surg. 66:1417–25. DOI: 10.1016/j.joms.2008.01.058. PMID: 18571026.

11. Hwang DY, On SW, Song SI. 2016; Bone regenerative effect of recombinant human bone morphogenetic protein-2 after cyst enucleation. Version 2. Maxillofac Plast Reconstr Surg. 38:22. DOI: 10.1186/s40902-016-0070-4. PMID: 27446821. PMCID: PMC4937077.

12. Chenard KE, Teven CM, He TC, Reid RR. 2012; Bone morphogenetic proteins in craniofacial surgery: current techniques, clinical experiences, and the future of personalized stem cell therapy. J Biomed Biotechnol. 2012:601549. DOI: 10.1155/2012/601549. PMID: 23226941. PMCID: PMC3511855.

13. Li RH, Wozney JM. 2001; Delivering on the promise of bone morphogenetic proteins. Trends Biotechnol. 19:255–65. DOI: 10.1016/S0167-7799(01)01665-1.

14. Geiger M, Li RH, Friess W. 2003; Collagen sponges for bone regeneration with rhBMP-2. Adv Drug Deliv Rev. 55:1613–29. DOI: 10.1016/j.addr.2003.08.010. PMID: 14623404.

15. Russell RG, Watts NB, Ebetino FH, Rogers MJ. 2008; Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int. 19:733–59. DOI: 10.1007/s00198-007-0540-8. PMID: 18214569.

16. Ihan Hren N, Miljavec M. 2008; Spontaneous bone healing of the large bone defects in the mandible. Int J Oral Maxillofac Surg. 37:1111–6. DOI: 10.1016/j.ijom.2008.07.008. PMID: 18760900.

17. Yim JH, Lee JH. 2009; Panoramic analysis about spontaneous bone regeneration after enucleation of jaw cyst. J Korean Assoc Maxillofac Plast Reconstr Surg. 31:229–36.