İlaçlara Bağlı Çene Kemiği Osteonekrozlarının Tedavisinde Kök Hücre Uygulamaları

Öz

Bifosfonatlar, osteoporoz ve Paget hastalığının tedavisinde metastatik kemik tümörlerinin önlenmesinde sıklıkla tercih edilen ilaçlardır. Bifosfonatlara bağlı gelişen çene kemiklerinde lokalize osteonekroz vakalarının artması; yaşam kalitesinin negatif olarak etkilenmesi ve morbiditenin artması araştırmacıları erken dönemde tanımlanmasına ve etkin tedavi şeklinin araştırılmasına yöneltmiştir. Bifosfonatların yanı sıra, diğer antirezorptif ve antianjiojenik ilaçların da çene kemiklerinde osteonekroza neden olabileceğinin anlaşılmasıyla, American Association of Oral and Maxillofacial Surgeons (AAOMS) ‘’bisfosfonata bağlı çene kemiği osteonekrozu (BİÇKON)” terminolojisinin “ ilaçlara bağlı çene kemiği osteonekrozu (İÇKON)’’ olarak değiştirilmesini önermiştir. Literatürde İÇKON vakalarının derlendiği birçok çalışma bulunmasına rağmen İÇKON tedavisinde kök hücre etkinliğine yönelik bir derleme çalışması bulunmamaktadır. Bu derlemenin amacı günümüzde birçok hastalığın tedavisinde kullanılan kök hücrelerin İÇKON tedavisindeki etkinliğini değerlendirmektir.

Anahtar Kelimeler

• Çene kemiği osteonekrozu
• antirezorptif tedavi
• ilaçla ilişkili osteonekroz
• kök hücre
• mezenkimal kök hücre

Stem Cell Therapies in Treatment of the Medication Related Osteonecrosis of the Jaw

Öz

Bisphosphonates are often preferred drugs for the treatment of osteoporosis, Paget's disease and in the prevention of metastatic bone tumors. The increase of localized osteonecrosis cases in jaw bones related to bisphosphonates; negative effects on quality of life and increased morbidity led researchers to identify early and to investigate the effective treatment modality. It was understood that in addition to bisphosphonates other antiresorptive and antiangiogenic drugs could cause osteonecrosis as well, so the American Association of Oral and Maxillofacial Surgeons (AAOMS) suggested to use "medication related osteonecrosis of jaw (MRONJ)" terminology instead of "bisphosphonate-related osteonecrosis of jaw (BRONJ)". Despite the fact that many studies about the MRONJ in the literature, there is no review of stem cell activity in the treatment of MRONJ. The aim of this review is to evaluate the efficacy of stem cell used in the treatment of many diseases, in the treatment of MRONJ.

Anahtar Kelimeler

• jaw bone osteonecrosis
• antiresoprtive therapy
• medication related osteonecrosis
• stem cell
• mesenchymal stem cell.

Kaynakça

1. 1. Gutta R, Louis P. Bisphosphonates and osteonecrosis of the jaws: Science and rationale. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104:186–93.
2. 2. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 2003;61:1115-7.
3. 3. Malan J, Ettinger K, Naumann E et al. The relationship of denosumab pharmacology and osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114: 671–76.
4. 4. Serra E, Paolantonio M, Spoto G, Mastrangelo F, Tete S, Dolci M. Bevacizumab- related osteneocrosis of the jaw. Int J Immunopathol Pharmacol. 2009;22:1121-23.
5. 5. Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, O'Ryan F. 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 2014;72:1938-56.
6. 6. Assael LA. Oral bisphosphonates as a cause of bisphosphonate-related osteonecrosis of the jaws: clinical findings, assessment of risks and preventive strategies. J Oral Maxillofac Surg 2009;67:35–43.
7. 7. Body JJ. Bisphosphonates for malignancy-related bone disease: current status, future developments. Support Care Cancer 2006;14:408–18.
8. 8. Stresing V, Daubiné F, Benzaid I. Bisphosphonates in cancer therapy. Cancer Lett 2007;257:16–35.

9. 9. Min You T, Lee KH, Lee SH. Denosumab-related osteonecrosis of the jaw: a case report and management based on pharmacokinetics. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2015;120:548–53.
10. 10. Qi WX, Tang LN, He AN, et al. Risk of osteonecrosis of the jaw in cancer patients receiving denosumab: a meta-analysis of seven randomized controlled trials. Int J Clin Oncol 2014;19:403–10.
11. 11. Ramírez L, López RM, Casañas E. New non-bisphosphonate drugs that produce osteonecrosis of the jaws. Oral Health Prev Dent 2015;13:385–93.
12. 12. Brunello A, Saia G, Bedogni A. Worsening of osteonecrosis of the jaw during treatment with sunitinib in a patient with metastatic renal cell carcinoma. Bone 2009;44:173–75.
13. 13. Santos-Silva AR, Belizario Rosa GA, Castro GD. Osteonecrosis of the mandible associated with bevacizumab therapy. Oral Surg Oral Med Oral Pathol Oral Radiol 2013;115:E32–E36.
14. 14. Hino S, Murase R, Terakado N, et al. Response of diffuse sclerosing osteomyelitis of the mandible to alendronate: follow-up study by 99mTc scintigraphy. Int J Oral Maxillofac Surg 2005; 34:576-8.
15. 15. van der Waal RI, Buter J, van der Waal I. Oral metastases: report of 24 cases. Br J Oral Maxillofac Surg 2003;41:3-6.
16. 17. Şahin O, Odabaşı O, Aliyev T, Tatar B. Risk factors of medication-related osteonecrosis of the jaw: a retrospective study in a Turkish subpopulation. J Korean Assoc Oral Maxillofac Surg 2019;45:108-15.
17. 18. Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G, Koutsoukou V, Gika D, Anagnostopoulos A, Papadimitriou C, Terpos E, Dimopoulos MA. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol 2005;23:8580-7.
18. 19. Woo SK, Hellstein JW, Kalmar JR. Systematic review: Bisphosphonates and osteonecrosis of the jaws. Ann Inter Med 2006;144: 753-61.
19. 20. Şahin O, Odabaşı O, Demiralp KÖ, Kurşun-Çakmak EŞ, Aliyev T. Comparison of findings of radiographic and fractal dimension analyses on panoramic radiographs of patients with early-stage and advanced-stage medication-related osteonecrosis of the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol 2019;128:78-86.
20. 21. Marx RE. A decade of bisphosphonate bone complications: what it has taught us about bone physiology. Int J Oral Maxillofac Implants 2014;29:e247–e258.
21. 22. Şahin O, Odabaşi O, Ekmekcioğlu C. Ultrasonic Piezoelectric Bone Surgery Combined With Leukocyte and Platelet-Rich Fibrin and Pedicled Buccal Fat Pad Flap in Denosumab-Related Osteonecrosis of the Jaw. J Craniofac Surg 2019;30:e434-e436.
22. 23. Bonacina R, MarianiU, Villa F,Villa A. Preventive strategies and clinical implications for bisphosphonate-related osteonecrosis of the jaw: a review of 282 patients. J Can Dent Assoc 2011;77:b147.
23. 24. Vandone AM, Donadio M, Mozzati M, Ardine M, Polimeni MA, Beatrice S, Ciuffreda L, Scoletta M. Impact of dental care in the prevention of bisphosphonate-associated osteonecrosis of the jaw: a single-center clinical experience. Ann Oncol Off J Eur Soc Med Oncol/ESMO 2012;23:193–200.
24. 25. Sahin O, Odabasi O. Serum Markers of Bone Turnover in Medication Related Osteonecrosis of the Jaw Patients. EC Dental Science 2018;17:504-10.
25. 26. Vescovi P, Merigo E, Meleti M. Conservative surgical management of stage I bisphosphonate-related osteonecrosis of the jaw. Int J Dent 2014;2014:107690.
26. 27. Fukushima Y, Enoki Y, Nakaoka C. Usability of surgical treatment in cases of bisphosphonate-related osteonecrosis of the jaw stage 2 with sequestrum. Ann Maxillofac Surg 2015;5:67–70.
27. 28. Vescovi P, Merigo E, Meleti M, Manfredi M. Bisphosphonate-associated osteonecrosis (BON) of the jaws: a possible treatment? Journal of Oral and Maxillofacial Surgery. 2006;64:1460–62.
28. 29. Nisi M, La Ferla F, Karapetsa D. Conservative surgical management of patients with bisphosphonate-related osteonecrosis of the jaw: a series of 120 patients. Br J Oral Maxillofac Surg 2016;54:930–35.
29. 30. Lerman MA, Xie W, Treister NS, Richardson PG, Weller EA, Woo SB. Conservative management of bisphosphonate-related osteonecrosis of the jaws: staging and treatment outcomes. Oral Oncol 2013;49: 977-83.
30. 31. Melea PI, Melakopoulos I, Kastritis E ,Tesseromatis C, Margaritis V, Dimopoulos MAve ark. Conservative treatment of bisphosphonate- related osteonecrosis of the jaw in multiple myeloma patients. Int J Dent 2014; 2014: 427273.
31. 32. Bodem JP, Schaal C, Kargus S. Surgical management of bisphosphonate-related osteonecrosis of the jaw stages II and III. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2016;121:367–72.
32. 33. Şahin O. Medication Related Osteonecrosis of the Jaw: What is the Key Point? Scientific Archives Of Dental Sciences 2019:2:1.
33. 34. Ripamonti CI, Cislaghi E, Mariani L, Maniezzo M. Efficacy and safety of medical ozone (O3) delivered in oil suspension applications for the treatment of osteonecrosis of the jaw in patients with bone metastases treated with bisphosphonates: preliminary results of a phase I-II study. Oral Oncology. 2011;47:185–90.
34. 35. Freiberger JJ. Utility of hyperbaric oxygen in treatment of bisphosphonate-related osteonecrosis of the jaws. Journal of Oral and Maxillofacial Surgery. 2009;67:96–106.
35. 36. Mendonca JJ, Juiz-Lopez P. Regenerative facial reconstruction of terminal stage osteoradionecrosis and other advanced craniofacial diseases with adult cultured stem and progenitor cells. Plast Reconstr Surg 2010;126:1699-709.
36. 37. Altay MA, Tasar F, Tosun E. Low-level laser therapy supported surgical treatment of bisphosphonate related osteonecrosis of jaws: a retrospective analysis of 11 cases. Photomed Laser Surg 2014;32:468–475.
37. 38. Keskinruzgar A, Bozdag Z, Aras MH, Demir T, Yolcu U, Cetiner S. Histopathological Effects of Teriparatide in Medication-Related Osteonecrosis of the Jaw: An Animal Study. J Oral Maxillofac Surg 2016;74:68-78.
38. 39. Epstein MS, Wicknick FW, Epstein JB, Berenson JR, Gorsky M. Management of bisphosphonate-associated osteonecrosis: pentoxifylline and tocopherol in addition to antimicrobial therapy. An initial case series. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:593–96.
39. 40. Bocanegra-Pèrez S, Vicente-Barrero M, Knezevic M. Use of platelet-rich plasma in the treatment of bisphosphonate related osteonecrosis of the jaw. Int J Oral Maxillofac Surg 2012;41:1410–15.
40. 41. Sahin O, Aliyev T, Tatar B. Leucocyte-rich and platelet-rich fibrin (L-PRF) for the treatment of medication-related osteonecrosis of the jaw (MRONJ) with long term follow-up. Biomed J Sci Tech Res 2018;2:1–3.
41. 42. Gönen ZB, Soylu E, Akbulut N. Maksillofasiyal Cerrahide Kök hücre Uygulamaları. Turkiye Klinikleri J Oral Maxillofac Surg- Special Topics 2016;2:36-41.
42. 43. Ogata K, Katagiri W, Osugi M, Kawai T, Sugimura Y, Hibi H, Nakamura S, Ueda M. Evaluation of the therapeutic effects of conditioned media from mesenchymal stem cells in a rat bisphosphonate-related osteonecrosis of the jaw-like model. Bone 2015;74:95–105.
43. 44. Osugi M, Katagiri W, Yoshimi R, Inukai T, Hibi H, Ueda M. Conditioned media from mesenchymal stem cells enhanced bone regeneration in rat calvarial bone defects. Tissue Eng Part A 2012;18:1479–89.
44. 45. Voss PJ, Matsumoto A, Alvarado E, Schmelzeisen R, Duttenhöfer F, Poxleitner P. Treatment of stage II medication-related osteonecrosis of the jaw with necrosectomy and autologous bone marrow mesenchymal stem cells. Odontology. 2017;105:484-93.
45. 46. Vescovi A, Gritti A, Cossu G, Galli R. Neural stem cells: plasticity and their transdifferentiation potential. Cells Tissues Organs. 2002;171:64-76.
46. 47. Weissman IL. Stem cells: units of development, units of regeneration, and units in evolution. Cell. 2000;100:157-68.
47. 48. Trounson A. The production and directed differentiation of human embryonic stem cells. Endocr Rev. 2006;27:208-19.
48. 49. Jacobsen LO, Marks EK, Robson MJ, et al. Effect of spleen protection on mortality floowing x-irradiation. J Lab Clin Med. 1949;34:1538.
49. 50. Lorenz E, Uphoff D, Reid TR, et al. Modification of irradiation injury in mice and guinea pigs by bone marrow injections. J Natl Cancer Inst 1951;12:197.
50. 51. Till JE, McCulloch EA. A direct measurement of the radiation sensivity of normal Mouse bone marrow cells. Radiat Res. 1961;14:213.
51. 52. Rimondini L, Mele S. Stem cell Technologies for tissue regeneration in dentistry. Minerva Stomatol 2009;58:483-500.
52. 53. Handa K, Saito M, Tsunoda A, Yamauchi M, Hattori S, Sato S, et al. Progenitor cells from dental follicle are able to form cementum matrix in vivo. Connect Tissue Res 2002;43:406-8.
53. 54. Koyama N, Okubo Y, Nakao K, Osawa K, Fujimura K, Bessho K. Pluripotency of mesenchymal cells derived from synovial fluid in patients with temporomandibular joint disorder. Life Sciences 2011;89:741-7.
54. 55. Porada CD, Almeida-Porada G. Mesenchymal stem cells as therapeutics and vehicles for gene and drug delivery. Adv Drug Deliv Rev 2010;62:1156-66.
55. 56. Behnia H, Khojasteh A, Soleimani M, Tehranchi A, Khoshzaban A, Keshel SH, et al. Secondary repair of alveolar clefts using human mesenchymal stem cells. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:1-6.
56. 57. Kim SH , Kim KH, Seo BM , Koo KT, Kim T, Seol YJ, Young K, Rhyu C, Chung CP, Lee YM. Alveolar bone regeneration by transplantation of periodontal ligament stem cells and bone marrow stem cells in canine peri-implant defects model: A pilot study. J Periodontol 2009;80:1815-23.
57. 58. Mesimaki K, Lindroos B, Tornwall J, Mauno J, Lindqvist C, Kontio R, et al. Novel maxillary reconstruction with ectopic bone formation by GMP adipose stemcells. Int J Oral Maxillofac Surg 2009;38:201-9.
58. 59. Rickert D, Sauerbier S, Nagursky H, Menne D, Vissink A, Raghoebar GM. Maxillary sinus floor elevation with bovine bone mineral combined with either autogenous bone or autogenous stem cells: a prospective randomized clinical trial. Clin Oral Implants Res 2010;22:251-8.
59. 60. Meijer GJ, deBruijn JD, Koole R, van Blitterswijk CA. Cell based bone tissue engineering in jaw defects. Biomaterials 2008;29:3053-61.
60. 61. Alkaisi A, Ismail AR, Mutum SS, Ahmad ZA, Masudi S, Abd Razak NH. Transplantation of human dental pulp stem cells: enhance bone consolidation in mandibular distraction osteogenesis. J Oral Maxillofac Surg. 2013;71:1758.e1-13.
61. 62. Shayesteh YS, Khojasteh A, Soleimani M, Alikhasi M, Khoshzaban A, Ahmadbeigi N. Sinus augmentation using human mesenchymal stem cells loaded into a beta-tricalcium phosphate/hydroxyapatite scaffold. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106:203-9.
62. 63. Matsuura Y, Atsuta I, Ayukawa Y, Yamaza T, Kondo R, Takahashi A, Ueda N, Oshiro W, Tsukiyama Y, Koyano K. Therapeutic interactions between mesenchymal stem cell for healing medication related osteonecrosis of the jaw. Stem Cell Res Ther 2016;7;119.
63. 64. Li Y, Xu J, Mao L, Liu Y, Gao R, Zheng Z, Chen W, Le A, Shi S, Wang S. Allogeneic mesenchymal stem cell therapy for bisphosphonate-related jaw osteonecrosis in Swine. Stem Cells Dev 2013;22:2047-56.
64. 65. Kaibuchi N, Iwata T, Yamato M, Okano T, Ando T. Multipotent mesenchymal stromal cell sheet therapy for bisphosphonate-related osteonecrosis of the jaw in a rat model. Acta Biomater. 2016;42:400-10.
65. 66. Şahin O. The Role of Dental Pulp Stem Cells in Oral and Maxillofacial Surgery. Scientific Archives Of Dental Sciences 2019;5:1.
66. 67. Cella L, Oppici A, Arbasi M, Moretto M, Piepoli M, Vallisa D, Zangrandi A, Di Nunzio C, Cavanna L. Autologous bone marrow stem cell intralesional transplantation repairing bisphosphonate related osteonecrosis of the jaw. Head Face Med. 2011;7:16.