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Odontology
Published in: Odontology 4/2017

01-10-2017 | Original Article

Treatment of stage II medication-related osteonecrosis of the jaw with necrosectomy and autologous bone marrow mesenchymal stem cells

Authors: Pit Jacob Voss, Akihiko Matsumoto, Esteban Alvarado, Rainer Schmelzeisen, Fabian Duttenhöfer, Philipp Poxleitner

Published in: Odontology | Issue 4/2017

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Abstract

Treatment strategies for medication-related osteonecrosis of the jaw (MRONJ) remain controversial. Although the AAOMS suggests a conservative approach, a surgical management with necrosectomy is often required when conservative management has failed. Moreover, recent studies have shown promising results using an early stage surgical treatment. Over the past decade, cell-based bone regeneration utilizing bone marrow mesenchymal stem cells (MSCs) received increased attention. MSCs are known to promote wound healing and induce new bone formation in compromised tissue. Accordingly, the aim of this study was to assess the role of MSCs in the management of MRONJ. This study included 6 patients referred to our department with the diagnosis of MRONJ. Upon informed consent, the patients underwent surgical resection of necrotic bone followed by MSCs grafting. The MSCs were separated from bone marrow cells aspirated from the iliac crest using a bone marrow aspirate concentrate system. The MSCs were grafted into the defect with autologous thrombin and the defect was covered with a collagen membrane. In all cases, bony edges were rounded and the wound was closed using a three-layered technique. In the follow-up from 12 to 54 months, all patients including those who had impaired conditions, sepsis, or pathological fracture, showed satisfactory healing with no signs of wound infection. This pilot study indicated that surgical management in combination with MSCs transplantation seems to be a promising treatment modality in the therapy of MRONJ.
Literature
1.
Aghaloo TL, Felsenfeld AL, Tetradis S. Osteonecrosis of the jaw in a patient on denosumab. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg. 2010;68(5):959–63.CrossRef
2.
Taylor KH, Middlefell LS, Mizen KD. Osteonecrosis of the jaws induced by anti-RANK ligand therapy. Br J Oral Maxillofac Surg. 2010;48(3):221–3.CrossRefPubMed
3.
Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, O’Ryan F. American association of oral and maxillofacial surgeons position paper on medication-related osteonecrosis of the jaw—2014 update. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg. 2014;72(10):1938–56.CrossRef
4.
Anastasilakis AD, Toulis KA, Polyzos SA, Anastasilakis CD, Makras P. Long-term treatment of osteoporosis: safety and efficacy appraisal of denosumab. Ther Clin Risk Manag. 2012;8:295–306.CrossRefPubMedPubMedCentral
5.
Rustemeyer J, Bremerich A. Bisphosphonate-associated osteonecrosis of the jaw: what do we currently know? A survey of knowledge given in the recent literature. Clin Oral Invest. 2010;14(1):59–64.CrossRef
6.
Hoff AO, Toth BB, Altundag K, Johnson MM, Warneke CL, Hu M, Nooka A, Sayegh G, Guarneri V, Desrouleaux K. Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Min Res Off J Am Soc Bone Min Res. 2008;23(6):826–36.CrossRef
7.
Agrillo A, Petrucci MT, Tedaldi M, Mustazza MC, Marino SM, Gallucci C, Iannetti G. New therapeutic protocol in the treatment of avascular necrosis of the jaws. J Craniofac Surg. 2006;17(6):1080–3.CrossRefPubMed
8.
Stockmann P, Vairaktaris E, Wehrhan F, Seiss M, Schwarz S, Spriewald B, Neukam FW, Nkenke E. Osteotomy and primary wound closure in bisphosphonate-associated osteonecrosis of the jaw: a prospective clinical study with 12 months follow-up. Support Care Cancer Off J Multinatl Assoc Support Care Cancer. 2010;18(4):449–60.
9.
Voss PJ, Joshi Oshero J, Kovalova-Muller A, Veigel Merino EA, Sauerbier S, Al-Jamali J, Lemound J, Metzger MC, Schmelzeisen R. Surgical treatment of bisphosphonate-associated osteonecrosis of the jaw: technical report and follow up of 21 patients. J Cranio Maxillo Facial Surg Off Publ Eur Assoc Cranio Maxillo Facial Surg. 2012;40(8):719–25.CrossRef
10.
Williamson RA. Surgical management of bisphosphonate induced osteonecrosis of the jaws. Int J Oral Maxillofac Surg. 2010;39(3):251–5.CrossRefPubMed
11.
Curi MM, Cossolin GS, Koga DH, Zardetto C, Christianini S, Feher O, Cardoso CL, dos Santos MO. Bisphosphonate-related osteonecrosis of the jaws–an initial case series report of treatment combining partial bone resection and autologous platelet-rich plasma. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg. 2011;69(9):2465–72.CrossRef
12.
Atalay B, Yalcin S, Emes Y, Aktas I, Aybar B, Issever H, Mandel NM, Cetin O, Oncu B. Bisphosphonate-related osteonecrosis: laser-assisted surgical treatment or conventional surgery? Lasers Med Sci. 2011;26(6):815–23.CrossRefPubMed
13.
Dong Y, Li Y, Huang C, Gao K, Weng X. Systemic application of teriparatide for steroid induced osteonecrosis in a rat model. BMC Musculoskel Disord. 2015;16:163.CrossRef
14.
Kakehashi H, Ando T, Minamizato T, Nakatani Y, Kawasaki T, Ikeda H, Kuroshima S, Kawakami A, Asahina I. Administration of teriparatide improves the symptoms of advanced bisphosphonate-related osteonecrosis of the jaw: preliminary findings. Int J Oral Maxillofac Surg. 2015;44(12):1558–64.CrossRefPubMed
15.
Cicciu M, Herford AS, Juodzbalys G, Stoffella E. Recombinant human bone morphogenetic protein type 2 application for a possible treatment of bisphosphonates-related osteonecrosis of the jaw. J Craniofac Surg. 2012;23(3):784–8.CrossRefPubMed
16.
Salamon A, Toldy E. Use of mesenchymal stem cells from adult bone marrow for injured tissue repair. Orv Hetil. 2009;150(27):1259–65.CrossRefPubMed
17.
Iohara K, Nakashima M, Ito M, Ishikawa M, Nakasima A, Akamine A. Dentin regeneration by dental pulp stem cell therapy with recombinant human bone morphogenetic protein 2. J Dent Res. 2004;83(8):590–5.CrossRefPubMed
18.
Sun Y, Feng Y, Zhang C. The effect of bone marrow mononuclear cells on vascularization and bone regeneration in steroid-induced osteonecrosis of the femoral head. Joint Bone Spine Revue du Rhumatisme. 2009;76(6):685–90.CrossRef
19.
Ueda M, Yamada Y, Ozawa R, Okazaki Y. Clinical case reports of injectable tissue-engineered bone for alveolar augmentation with simultaneous implant placement. Int J Periodontics Restor Dent. 2005;25(2):129–37.
20.
21.
Warren SM, Fong KD, Chen CM, Loboa EG, Cowan CM, Lorenz HP, Longaker MT. Tools and techniques for craniofacial tissue engineering. Tissue Eng. 2003;9(2):187–200.CrossRefPubMed
22.
Sauerbier S, Stubbe K, Maglione M, Haberstroh J, Kuschnierz J, Oshima T, Xavier SP, Brunnberg L, Schmelzeisen R, Gutwald R. Mesenchymal stem cells and bovine bone mineral in sinus lift procedures—an experimental study in sheep. Tissue Eng C Methods. 2010;16(5):1033–9.CrossRef
23.
Freiberger JJ, Padilla-Burgos R, Chhoeu AH, Kraft KH, Boneta O, Moon RE, Piantadosi CA. Hyperbaric oxygen treatment and bisphosphonate-induced osteonecrosis of the jaw: a case series. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg. 2007;65(7):1321–7.CrossRef
24.
Muschler GF, Boehm C, Easley K. Aspiration to obtain osteoblast progenitor cells from human bone marrow: the influence of aspiration volume. J Bone Joint Surg Am Vol. 1997;79(11):1699–709.CrossRef
25.
Gutwald R, Haberstroh J, Kuschnierz J, Kister C, Lysek DA, Maglione M, Xavier SP, Oshima T, Schmelzeisen R, Sauerbier S. Mesenchymal stem cells and inorganic bovine bone mineral in sinus augmentation: comparison with augmentation by autologous bone in adult sheep. Br J Oral Maxillofac Surg. 2010;48(4):285–90.CrossRefPubMed
26.
Schmelzeisen R, Gutwald R, Oshima T, Nagursky H, Vogeler M, Sauerbier S. Making bone II: maxillary sinus augmentation with mononuclear cells—case report with a new clinical method. Br J Oral Maxillofac Surg. 2011;49(6):480–2.CrossRefPubMed
27.
Duttenhoefer F, Hieber SF, Stricker A, Schmelzeisen R, Gutwald R, Sauerbier S. Follow-up of implant survival comparing ficoll and bone marrow aspirate concentrate methods for hard tissue regeneration with mesenchymal stem cells in humans. BioRes Open Access. 2014;3(2):75–6.CrossRefPubMedPubMedCentral
28.
Sauerbier S, Stricker A, Kuschnierz J, Buhler F, Oshima T, Xavier SP, Schmelzeisen R, Gutwald R. In vivo comparison of hard tissue regeneration with human mesenchymal stem cells processed with either the FICOLL method or the BMAC method. Tissue Eng C Methods. 2010;16(2):215–23.CrossRef
29.
Elda S, Czerninski R, Avgil M, Or R. Hematopoietic stem cells local transplantation for the treatment of osteonecrosis of the jaws. Support Care Cancer. 2005;13:455.
30.
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.CrossRefPubMedPubMedCentral
31.
Fournier P, Boissier S, Filleur S, Guglielmi J, Cabon F, Colombel M, Clezardin P. Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. Cancer Res. 2002;62(22):6538–44.PubMed
32.
Gonzalvez-Garcia M, Rodriguez-Lozano FJ, Villanueva V, Segarra-Fenoll D, Rodriguez-Gonzalez MA, Onate-Sanchez R, Blanquer M, Meseguer-Olmo L, Moraleda JM. Mesenchymal stem cells and bisphosphonate-related osteonecrosis of the jaw: the future? Oral Dis. 2012;18(8):823–4.CrossRefPubMed
33.
Gruber R, Mayer C, Schulz W, Graninger W, Peterlik M, Watzek G, Luyten FP, Erlacher L. Stimulatory effects of cartilage-derived morphogenetic proteins 1 and 2 on osteogenic differentiation of bone marrow stromal cells. Cytokine. 2000;12(11):1630–8.CrossRefPubMed
34.
Reddi AH. Cartilage morphogenetic proteins: role in joint development, homoeostasis, and regeneration. Ann Rheum Dis. 2003;62(Suppl 2):ii73–8.PubMedPubMedCentral
35.
Tsumaki N, Tanaka K, Arikawa-Hirasawa E, Nakase T, Kimura T, Thomas JT, Ochi T, Luyten FP, Yamada Y. Role of CDMP-1 in skeletal morphogenesis: promotion of mesenchymal cell recruitment and chondrocyte differentiation. J Cell Biol. 1999;144(1):161–73.CrossRefPubMedPubMedCentral
36.
Kos M, Brusco D, Kuebler J, Engelke W. Clinical comparison of patients with osteonecrosis of the jaws, with and without a history of bisphosphonates administration. Int J Oral Maxillofac Surg. 2010;39(11):1097–102.CrossRefPubMed
37.
Mast G, Otto S, Mucke T, Schreyer C, Bissinger O, Kolk A, Wolff KD, Ehrenfeld M, Sturzenbaum SR, Pautke C. Incidence of maxillary sinusitis and oro-antral fistulae in bisphosphonate-related osteonecrosis of the jaw. J Cranio Maxillo Facial Surg Off Publ Eur Assoc Cranio Maxillo Facial Surg. 2012;40(7):568–71.CrossRef
38.
Pautke C, Bauer F, Tischer T, Kreutzer K, Weitz J, Kesting M, Holzle F, Kolk A, Sturzenbaum SR, Wolff KD. Fluorescence-guided bone resection in bisphosphonate-associated osteonecrosis of the jaws. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg. 2009;67(3):471–6.CrossRef
39.
Fleisher KE, Doty S, Kottal S, Phelan J, Norman RG, Glickman RS. Tetracycline-guided debridement and cone beam computed tomography for the treatment of bisphosphonate-related osteonecrosis of the jaw: a technical note. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg. 2008;66(12):2646–53.CrossRef
40.
Wilde F, Heufelder M, Winter K, Hendricks J, Frerich B, Schramm A, Hemprich A. 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. 2011;111(2):153–63.CrossRefPubMed
41.
Lemound J, Eckardt A, Kokemuller H, von See C, Voss PJ, Tavassol F, Rucker M, Rana M, Gellrich NC. Bisphosphonate-associated osteonecrosis of the mandible: reliable soft tissue reconstruction using a local myofascial flap. Clin Oral Invest. 2012;16(4):1143–52.CrossRef
42.
Khan AA, Sandor GK, Dore E, Morrison AD, Alsahli M, Amin F, Peters E, Hanley DA, Chaudry SR, Dempster DW. Canadian consensus practice guidelines for bisphosphonate associated osteonecrosis of the jaw. J Rheum. 2008;35(7):1391–7.PubMed
43.
Yoneda T, Hagino H, Sugimoto T, Ohta H, Takahashi S, Soen S, Taguchi A, Toyosawa S, Nagata T, Urade M. Bisphosphonate-related osteonecrosis of the jaw: position paper from the Allied Task Force Committee of Japanese Society for Bone and Mineral Research, Japan Osteoporosis Society, Japanese Society of Periodontology, Japanese Society for Oral and Maxillofacial Radiology, and Japanese Society of Oral and Maxillofacial Surgeons. J Bone Min Metab. 2010;28(4):365–83.CrossRef
44.
Marx RE. Reconstruction of defects caused by bisphosphonate-induced osteonecrosis of the jaws. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg. 2009;67(5 Suppl):107–19.CrossRef
45.
Bartl R. Practical guidelines for the management of osteoporosis–evidence-based and cost-effective. Dtsch Med Wochenschr. 2007;132(18):995–9.CrossRefPubMed
46.
Otto S, Troltzsch M, Jambrovic V, Panya S, Probst F, Ristow O, Ehrenfeld M, Pautke C. Tooth extraction in patients receiving oral or intravenous bisphosphonate administration: a trigger for BRONJ development? J Cranio Maxillo Facial Surg Off Publ Eur Assoc Cranio Maxillo Facial Surg. 2015;43(6):847–54.CrossRef
47.
Wilde F, Hendricks J, Riese C, Pausch NC, Schramm A, Heufelder M. Bone regeneration without bone grafting after resection of a segment of the mandible to treat bisphosphonate-related osteonecrosis of the jaw. J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg. 2011;69(10):2657–62.CrossRef
48.
Hellstein JW, Marek CL. Bisphosphonate osteochemonecrosis (bis-phossy jaw): is this phossy jaw of the 21st century? J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg. 2005;63(5):682–9.CrossRef
49.
Russell RG, Watts NB, Ebetino FH, Rogers MJ. Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA. 2008;19(6):733–59.CrossRef
50.
Allegra A, Oteri G, Nastro E, Alonci A, Bellomo G, Del Fabro V, Quartarone E, Alati C, De Ponte FS, Cicciu D. Patients with bisphosphonates-associated osteonecrosis of the jaw have reduced circulating endothelial cells. Hematol Oncol. 2007;25(4):164–9.CrossRefPubMed
51.
Kikuiri T, Kim I, Yamaza T, Akiyama K, Zhang Q, Li Y, Chen C, Chen W, Wang S, Le AD. Cell-based immunotherapy with mesenchymal stem cells cures bisphosphonate-related osteonecrosis of the jaw-like disease in mice. J Bone Min Res Off J Am Soc Bone Min Res. 2010;25(7):1668–79.CrossRef
52.
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(14):2047–56.CrossRefPubMedPubMedCentral
Metadata
Title
Treatment of stage II medication-related osteonecrosis of the jaw with necrosectomy and autologous bone marrow mesenchymal stem cells
Authors
Pit Jacob Voss
Akihiko Matsumoto
Esteban Alvarado
Rainer Schmelzeisen
Fabian Duttenhöfer
Philipp Poxleitner
Publication date
01-10-2017
Publisher
Springer Japan
Published in
Odontology / Issue 4/2017
Print ISSN: 1618-1247
Electronic ISSN: 1618-1255
DOI
https://doi.org/10.1007/s10266-017-0295-4

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