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The effect of concentrated growth factor (CGF) in the surgical treatment of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients: a randomized controlled study

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Abstract

Objectives

The purpose of this present study was to evaluate the efficiency of the growth factors delivered by concentrated growth factor (CGF) on the healing process of osteoporotic patients with medication-related osteonecrosis of the jaws (MRONJ).

Methods

This randomized controlled study was composed of osteoporotic female patients who were treated with oral bisphosphonates (BPs) and diagnosed with MRONJ. For the CGF group, each patient was treated with a local application of CGF at the surgical site after removing the necrotic bone, while the surgical area was primarily closed as traditional surgical therapy for the control group. The patients underwent clinical examinations for 6 months postoperatively to check the presence of infection and dehiscence.

Results

Complete healing was achieved in 19 patients of 28 patients (mean age: CGF group, 73.57 ± 5.1; control group, 73.64 ± 5.49) diagnosed with MRONJ. There was no significant difference in post-op healing data between groups during healing periods (p > 0.05). In the CGF group (n = 14) in three cases, bone exposure without infection was detected, and one of them showed a recurrent infection. In the control group (n = 14) in six cases, bone exposure without infection was detected, and three of them also showed recurrent infection.

Conclusion

Although our results were not statistically significant, our findings suggest that the local application of CGF appears to be an effective approach to the surgical treatment of MRONJ in osteoporosis patients by improving tissue regeneration.

Clinical relevance

A specific treatment protocol to manage MRONJ is still controversial. This study justifies that CGF can be used in combination with surgical treatment.

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References

  1. Aljohani S, Fliefel R, Ihbe J, Kühnisch J, Ehrenfeld M, Otto S (2017) What is the effect of anti-resorptive drugs (ARDs) on the development of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients: a systematic review. J Cranio-Maxillofac Surg 45:1493–1502. https://doi.org/10.1016/j.jcms.2017.05.028

    Article  Google Scholar 

  2. Nisi M, Karapetsa D, Gennai S, Ramaglia L, Graziani F, Gabriele M (2018) Conservative surgical treatment of medication related osteonecrosis of the jaw (MRONJ) lesions in patients affected by osteoporosis exposed to oral bisphosphonates: 24 months follow-up. J Cranio-Maxillofac Surg 46:1153–1158. https://doi.org/10.1016/j.jcms.2018.05.003

    Article  Google Scholar 

  3. Sarkarat F, Motamedi MHK, Jahanbani J, Sepehri D, Kahali R, Nematollahi Z (2014) Platelet-rich plasma in treatment of zoledronic acid-induced bisphosphonate-related osteonecrosis of the jaws. Trauma Mon 19(2). https://doi.org/10.5812/traumamon.17196

  4. Barba-Recreo P, Georgiev-Hristov T, Bravo-Burguillos ER, Abarrategi A, Burgueño M, García-Arranz M (2015) Adipose-derived stem cells and platelet-rich plasma for preventive treatment of bisphosphonate-related osteonecrosis of the jaw in a murine model. J Cranio-Maxillofac Surg 43(7):1161–1168. https://doi.org/10.1016/j.jcms.2015.04.026

    Article  Google Scholar 

  5. Obinata K, Shirai S, Ito H, Nakamura M, Carrozzo M, Macleod I, Carr A, Yamazaki Y, Tei K (2017) Image findings of bisphosphonate related osteonecrosis of jaws comparing with osteoradionecrosis. Dentomaxillofac Radiol 46(5). https://doi.org/10.1259/dmfr.20160281

  6. Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, O'Ryan F (2014) American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw—2014 update. J Oral Maxillofac Surg 72:1938–1956. https://doi.org/10.1016/j.joms.2014.04.031

    Article  PubMed  Google Scholar 

  7. Nørholt SE, Hartlev J (2016) Surgical treatment of osteonecrosis of the jaw with the use of platelet-rich fibrin: a prospective study of 15 patients. Int J Oral Maxillofac Surg 45(10):1256–1260. https://doi.org/10.1016/j.ijom.2016.04.010

    Article  PubMed  Google Scholar 

  8. Tsai LL, Huang YF, Chang YC (2016) Treatment of bisphosphonate-related osteonecrosis of the jaw with platelet-rich fibrin. J Formos Med Assoc 115:585–586. https://doi.org/10.1016/j.jfma.2015.10.005

    Article  PubMed  Google Scholar 

  9. Miksad RA, Lai KC, Dodson TB, Woo SB, Treister NS, Akinyemi O, Bihrle M, Maytal G, August M, Gazelle GS, Swan JS (2011) Quality of life implications of bisphosphonate-associated osteonecrosis of the jaw. Oncologist 16:121–132. https://doi.org/10.1634/theoncologist.2010-0183

    Article  PubMed  PubMed Central  Google Scholar 

  10. Mauceri R, Panzarella V, Maniscalco L, Bedogni A, Licata ME, Albanese A, Toia F, Cumbo EMG, Mazzola G, di Fede O, Campisi G (2018) Conservative surgical treatment of bisphosphonate-related osteonecrosis of the jaw with Er, Cr: YSGG laser and platelet-rich plasma: a longitudinal study. Biomed Res Int 2018:3982540. https://doi.org/10.1155/2018/3982540

    Article  PubMed  PubMed Central  Google Scholar 

  11. Sohn DS, Heo JU, Kwak DH, Kim DE Kim JM, Moon JW, Lee JH, Park IS (2011) Bone regeneration in the maxillary sinus using an autologous fibrin-rich block with concentrated growth factors alone. Implant Dent 20(5):389–395. https://doi.org/10.1097/ID.0b013e31822f7a70

    Article  PubMed  Google Scholar 

  12. Lin SL, Wu SL, Tsai CC, Ko SY, Chiang WF, Yang JW (2016) The use of solid-phase concentrated growth factors for surgical defects in the treatment of dysplastic lesions of the oral mucosa. J Oral Maxillofac Surg 74(12):2549–2556. https://doi.org/10.1016/j.joms.2016.06.183

    Article  PubMed  Google Scholar 

  13. Ramaglia L, Guida A, Iorio-Siciliano V, Cuozzo A, Blasi A, Sculean A (2018) Stage-specific therapeutic strategies of medication-related osteonecrosis of the jaws: a systematic review and meta-analysis of the drug suspension protocol. Clin Oral Investig 22:597–615. https://doi.org/10.1007/s00784-017-2325-6

    Article  PubMed  Google Scholar 

  14. Lopes RN, Rabelo GD, Rocha AC (2015) Surgical therapy for bisphosphonate-related osteonecrosis of the jaw: six year experience of a single institution. J Oral Maxillofac Surg 73(7):1288–1295. https://doi.org/10.1016/j.joms.2015.01.008

    Article  PubMed  Google Scholar 

  15. Bodem JP, Schaal C, Kargus S (2016) Surgical management of bisphosphonate-related osteonecrosis of the jaw stages II and III. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 121(4):367–372. https://doi.org/10.1016/j.oooo.2015.10.033

    Article  Google Scholar 

  16. Wilde F, Heufelder M, Winter K (2011) The role of surgical therapy in the management of intravenous bisphosphonates-related osteonecrosis of the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 111(2):153–163. https://doi.org/10.1016/j.tripleo.2010.04.015

    Article  PubMed  Google Scholar 

  17. Ristow O, Otto S, GeiB C et al (2017) Comparison of auto-fluorescence and tetracycline fluorescence for guided bone surgery of medication-related osteonecrosis of the jaw: a randomized controlled feasibility study. Int J Oral Maxillofac Surg 46:157–166. https://doi.org/10.1016/j.ijom.2016.10.008

    Article  PubMed  Google Scholar 

  18. 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 75:1176–1184. https://doi.org/10.1016/j.joms.2016.12.005

    Article  PubMed  Google Scholar 

  19. Ustaoglu G, Bulut DG, Gümüs KC (2019) Evaluation of different platelet-rich concentrates effects on early soft tissue healing and socket preservation after tooth extraction. J Stomatol Oral Maxillofac Surg. https://doi.org/10.1016/j.jormas.2019.09.005

  20. Ikeda T, Kuraguchi J, Kogashiwa Y, Yokoi H, Satomi T, Kohno N (2015) Successful treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) patients with sitafloxacin: new strategies for the treatment of BRONJ. Bone 73:217–222. https://doi.org/10.1016/j.bone.2014.12.021

    Article  PubMed  Google Scholar 

  21. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Zheng M, Zoledronic Acid Prostate Cancer Study Group (2004) Zoledronic acid prostate cancer study group. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 96(11):879–882. https://doi.org/10.1093/jnci/djh141

    Article  PubMed  Google Scholar 

  22. Mavrokokki T, Cheng A, Stein B, Goss A (2007) Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg 65:415–423. https://doi.org/10.1016/j.joms.2006.10.061

    Article  PubMed  Google Scholar 

  23. Bagan L, Jiménez Y, Leopoldo M, Murillo-Cortes J, Bagan J (2007) Exposed necrotic bone in 183 patients with bisphosphonate-related osteonecrosis of the jaw: associated clinical characteristics. Med Oral Patol Oral Cir Bucal 22(5):582. https://doi.org/10.4317/medoral.22133

    Article  Google Scholar 

  24. Assael LA (2009) Oral bisphosphonates as a cause of bisphosphonate-related osteonecrosis of the jaws: clinical findings, assessment of risks, and preventive strategies. J Oral Maxillofac Surg 67:35–43. https://doi.org/10.1016/j.joms.2009.01.003

    Article  PubMed  Google Scholar 

  25. Mânea HC, Urechescu HC, Balica NC et al (2018) Bisphosphonates-induced osteonecrosis of the jaw–epidemiological, clinical and histopathological aspects. Romanian J Morphol Embryol 59(3):825–831

    Google Scholar 

  26. Marx RE (2009) Reconstruction of defects caused by bisphosphonate-induced osteonecrosis of the jaws J Oral Maxillofac Surg 67(5): 107–119. https://doi.org/10.1016/j.joms.2008.12.007

  27. British Dental Association, Bisphosphonates Fact File, British Dental Association, London, 2008

  28. Del Fabbro M, Gallesio G, Mozzati M (2015) Autologous platelet concentrates for bisphosphonate-related osteonecrosis of the jaw treatment and prevention. A systematic review of the literature. Eur J Cancer 51(1):62–74. https://doi.org/10.1016/j.ejca.2014.10.015

    Article  PubMed  Google Scholar 

  29. Bielecki TM, Gazdzik TS, Arendt J, Szczepanski T, Kròl W, Wielkoszynski T (2007) Antibacterial effect of autologous platelet gel enriched with growth factors and other active substances: an in vitro study. J Bone Joint Surg (Br) 89:417–420. https://doi.org/10.1302/0301-620X.89B3.18491

    Article  Google Scholar 

  30. Waiker VP, Shivalingappa S (2015) Comparison between conventional mechanical fixation and use of autologous platelet rich plasma (PRP) in wound beds prior to resurfacing with split thickness skin graft. World J Plastic Surg 4(1):50 https://www.ncbi.nlm.nih.gov/pubmed/25606477

    Google Scholar 

  31. Mozzati M, Arata V, Gallesio G (2012) Tooth extraction in patients on zoledronic acid therapy. Oral Oncol 48(9):817–821. https://doi.org/10.1016/j.oraloncology.2012.03.009

    Article  PubMed  Google Scholar 

  32. Coviello V, Peluso F, Dehkhargani SZ, Verdugo F, Raffaelli LUCA, Manicone PF (2012) Platelet-rich plasma improves wound healing in multiple myeloma bisphosphonate-associated osteonecrosis of the jaw patients. J Biol Regul Homeost Agents 26(1):151–155

    PubMed  Google Scholar 

  33. Longo F, Guida A, Aversa C, Pavone E, Di Costanzo G, Ramaglia L, Ionna F (2014) Platelet rich plasma in the treatment of bisphosphonate-related osteonecrosis of the jaw: personal experience and review of the literature. Int J Dent 2014:298945. https://doi.org/10.1155/2014/298945

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kim JW, Kim SJ, Kim MR (2014) Leucocyte-rich and platelet-rich fibrin for the treatment of bisphosphonate-related osteonecrosis of the jaw: a prospective feasibility study. Brit J Oral Maxillofac Surg 52(9):854–859. https://doi.org/10.1016/j.bjoms.2014.07.256

    Article  Google Scholar 

  35. Li X, Yang H, Zhang Z, Yan Z, Lv H, Zhang Y, Wu B (2019) Concentrated growth factor exudate enhances the proliferation of human periodontal ligament cells in the presence of TNF-α. Mol Med Rep 19(2):943–950. https://doi.org/10.3892/mmr.2018.9714

    Article  PubMed  Google Scholar 

  36. Borsani E, Bonazza V, Buffoli B et al (2018) Beneficial effects of concentrated growth factors and resveratrol on human osteoblasts in vitro treated with bisphosphonates. Biomed Res Int 2018:1–13. https://doi.org/10.1155/2018/4597321

    Article  Google Scholar 

  37. Qiao J, Duan J, Zhang Y, Chu Y, Sun C (2016) The effect of concentrated growth factors in the treatment of periodontal intrabony defects. Future Sci OA 2(4):FS136. https://doi.org/10.4155/fsoa-2016-0019

    Article  PubMed  PubMed Central  Google Scholar 

  38. Bozkurt Dogan S, Ongoz Dede F, Balli U, Atalay EN, Durmuslar MC (2015) Concentrated growth factor in the treatment of adjacent multiple gingival recessions: a Split-mouth randomized clinical trial. J Clin Periodontol 42(9):868–875. https://doi.org/10.1111/jcpe.12444

    Article  PubMed  Google Scholar 

  39. Rodella LF, Favero G, Boninsegna R, Buffoli B, Labanca M, Scari G, Sacco L, Batani T, Rezzani R (2011) Growth factors, CD34 positive cells, and fibrin network analysis in concentrated growth factors fraction. Microsc Res Tech 74:772–777. https://doi.org/10.1002/jemt.20968

    Article  PubMed  Google Scholar 

  40. Kim TH, Kim SH, Sandor GK, Kim YD (2014) Comparison of platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and concentrated growth factor (CGF) in rabbit-skull defect healing. Arch Oral Biol 59:550–558. https://doi.org/10.1016/j.archoralbio.2014.02.004

    Article  PubMed  Google Scholar 

  41. Chen Y, Cai Z, Zheng D, Lin P, Cai Y, Hong S, Lai Y, Wu D (2016) Inlay osteotome sinus floor elevation with concentrated growth factor application and simultaneous short implant placement in severely atrophic maxilla. Sci Rep 6:27348. https://doi.org/10.1038/srep27348

    Article  PubMed  PubMed Central  Google Scholar 

  42. Choi YS, Kim YC, Ji S, Choi Y (2014) Increased bacterial invasion and differential expression of tight-junction proteins, growth factors, and growth factor receptors in periodontal lesions. J Periodontol 85:e313–e322. https://doi.org/10.1902/jop.2014.130740

    Article  PubMed  Google Scholar 

  43. Lee JW, Kwon OH, Kim TK, Cho YK, Choi KY, Chung HY, Cho BC, Yang JD, Shin CH (2013) Platelet-rich plasma: quantitative assessment of growth factor levels and comparative analysis of activated and inactivated groups. Arch Plast Surg 40:530–535. https://doi.org/10.5999/aps.2013.40.5.530

    Article  PubMed  PubMed Central  Google Scholar 

  44. Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJJ, Mouhyi J, Gogly B (2006) Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part II: platelet-related biologic features. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101:e45–e50. https://doi.org/10.1016/j.tripleo.2005.07.009

    Article  PubMed  Google Scholar 

  45. Qiao J, An N, Quyang X (2017) Quantification of growth factors in different platelet concentrates. Platelets 28:774–778. https://doi.org/10.1080/09537104.2016.1267338

    Article  PubMed  Google Scholar 

  46. Qin J, Wang L, Zheng L, Zhou X, Zhang Y, Yang T, Zhou Y (2016) Concentrated growth factor promotes Schwann cell migration partly through the integrin b1-mediated activation of the focal adhesion kinase pathway. Int J Mol Med 37:1363–1370. https://doi.org/10.3892/ijmm.2016.2520

    Article  PubMed  Google Scholar 

  47. Takahashi A, Tsujino T, Yamaguchi S, Isobe K, Watanabe T, Kitamura Y, Okuda K, Nakata K, Kawase T (2019) Distribution of platelets, transforming growth factor-β1, platelet-derived growth factor-BB, vascular endothelial growth factor and matrix metalloprotease-9 in advanced platelet-rich fibrin and concentrated growth factor matrices. J Investig Clin Dent 10(4):e12458. https://doi.org/10.1111/jicd.12458

    Article  PubMed  Google Scholar 

  48. Pichardo SEC, van Merkesteyn RJP (2016) Evaluation of a surgical treatment of denosumab-related osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol 122:272–278. https://doi.org/10.1016/j.oooo.2016.03.008

    Article  PubMed  Google Scholar 

  49. O’Halloran M, Boyd NM, Smith A (2014) Denosumab and osteonecrosis of the jaws – the pharmacology, pathogenesis and a report of two cases. Aust Dent J 59:516–519. https://doi.org/10.1111/adj.12217

    Article  PubMed  Google Scholar 

  50. Diniz-Freitas M, Fernandez-Feijoo J, Dios PD, Pousa X, Limeras J (2018) Denosumab-related osteonecrosis of the jaw following non-surgical periodontal therapy: a case report. J Clin Periodontol 45:570–577. https://doi.org/10.1111/jcpe.12882

    Article  PubMed  Google Scholar 

  51. Fukumoto S, Matsumoto T (2017) Recent advances in the management of osteoporosis. F1000Res 6:625. https://doi.org/10.12688/f1000research.10682.1

    Article  PubMed  PubMed Central  Google Scholar 

  52. Epstein MS, Ephros HD, Epstein JB (2013) Review of current literature and implications of RANKL inhibitors for oral health care providers. Oral Surg Oral Med Oral Pathol Oral Radiol 116:e437–e442. https://doi.org/10.1016/j.oooo.2012.01.046

    Article  PubMed  Google Scholar 

  53. Robinson A, Scully C (2014) Pharmacology: new therapies and challenges. Br Dent J 217:258–259. https://doi.org/10.1038/sj.bdj.2014.811

    Article  PubMed  Google Scholar 

  54. Hasegawa T, Kawakita A, Ueda N, Funahara R, Tachibana A, Kobayashi M et al (2017) A multicenter retrospective study of the risk factors associated with medication-related osteonecrosis of the jaw after tooth extraction in patients receiving oral bisphosphonate therapy: can primary wound closure and a drug holiday really prevent MRONJ? Osteoporos Int 28(8):2465–2473. https://doi.org/10.1007/s00198-017-4063-7

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Ege University, Izmir, Turkey

    Meltem Ozden Yüce & Gözde Işık

  2. Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Izmir Democracy University, Izmir, Turkey

    Emine Adalı

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Yüce, M.O., Adalı, E. & Işık, G. The effect of concentrated growth factor (CGF) in the surgical treatment of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients: a randomized controlled study. Clin Oral Invest 25, 4529–4541 (2021). https://doi.org/10.1007/s00784-020-03766-8

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