Analysis of different therapeutic protocols for osteonecrosis of the jaw associated with oral and intravenous bisphpsphonates

  1. Elena Beatriz Bermúdez Bejarano 2
  2. María Angeles Serrera Figallo 1
  3. Aida Gutiérrez Corrales 2
  4. Manuel María Romero Ruiz 2
  5. Raquel Castillo de Oyagüe 3
  6. José Luis Gutiérrez Pérez 2
  7. Guillermo Machuca-Portillo 4
  8. Daniel Torres Lagares 2
  1. 1 Associate Professor. Master’s in Integrated Dentistry and Patients with Special Diseases. School of Dentistry. University of Seville
  2. 2 Master’s Degree in Oral Surgery. School of Dentistry. University of Seville
  3. 3 Department of Stomatology. School of Dentistry. Complutense University of Madrid
  4. 4 Professor of Integrated. Dentistry and Patients with Special Diseases. School of Dentistry. University of Seville
Revista:
Medicina oral, patología oral y cirugía bucal. Ed. inglesa

ISSN: 1698-6946

Año de publicación: 2017

Volumen: 22

Número: 1

Páginas: 18

Tipo: Artículo

DOI: 10.4317/MEDORAL.21477 DIALNET GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Medicina oral, patología oral y cirugía bucal. Ed. inglesa

Resumen

Chemotherapy-associated osteonecrosis of the jaw caused by bisphosphonates is an exposure of necrotic bone with more than eight weeks of evolution that is attributable to bisphosphonates and no prior radiation therapy. Its etiopathogenesis remains unknown, although there are two hypotheses that may explain it: the drug’s mechanism of action, and the risk factors that can lead to osteonecrosis. There is a wide range of treatment options for managing chemotherapy-associated osteonecrosis of the jaw, from conservative treatments to surgical procedures of varying levels of invasiveness, which are sometimes supplemented with adjuvant therapies. The objective of this article is to group the therapeutic options for osteonecrosis of the jaw (ONJ) into seven different protocols and to evaluate their effectiveness in relation to stage of ONJ. A literature review was carried out in PubMed following the PRISMA criteria. A total of 47 were collected after compiling a series of variables that define ONJ, applied treatments, and the clinical results obtained. The 47 articles selected have a low to average estimated risk of bias and are of moderate to good quality. According to the data obtained, Protocol 3 (conservative treatment, clinical and radiological follow-up, minimally invasive surgical treatment, and adjuvant therapies) is the most favorable approach for ONJ lesions caused by oral bisphosphonates. For lesions caused by intravenous bisphosphonates, Protocol 2 (conservative treatment, clinical and radiological follow-up, minimally invasive surgical treatment, and no adjuvant therapies) is the best approach. When comparing the different stages of ONJ, Protocol 1 (conservative treatment, clinical and radiological follow-up) promotes better healing of Stage 1 ONJ lesions caused by orally administered bisphosphonates, and Protocol 3 is recommended for Stage II. For ONJ lesions attributable to intravenous bisphosphonates, Protocol 7 (conservative treatment, clinical and radiological follow-up, and adjuvant therapies) provides the best results in Stage 0; in Stages I, II, and III, Protocol 1 gives better results.

Referencias bibliográficas

  • 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
  • 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 jaws--2009 update. J Oral Maxillofac Surg. 675. 2-12
  • Fliefel, R, Tröltzsch, M, Kühnisch, J, Ehrenfeld, M, Otto, S. (2015). Treatment strategies and outcomes of bisphosphonate-related osteonecrosis of the jaw (BRONJ) withcharacterization of patients: a systematic review. Int J Oral Maxillofac Surg. 44. 568
  • Ruggiero, SL, Dodson, TB, Fantasia, J, Goodday, R, Aghaloo, T, Mehrotra, B. (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
  • Vidal-Real, C, Pérez-Sayáns, M, Suárez-Peñaranda, JM, Gándara-Rey, JM, García-García, A. (2015). Osteonecrosis of the jaws in 194 patients who have undergone intravenous bisphosphonate therapy in Spain. Med Oral Patol Oral Cir Bucal. 20. 267
  • Gavaldá, C, Bagán, JV. (2016). Concept, diagnosis and classification of bisphosphonate-associated osteonecrosis of the jaws. A review of the literature. Med Oral Patol Oral Cir Bucal. 21. 260
  • Leizaola-Cardesa, IO, Aguilar-Salvatierra, A, Gonzalez-Jaranay, M, Moreu, G, Sala-Romero, MJ, Gómez-Moreno, G. (2016). Bisphosphonates, vitamin D, parathyroid hormone, and osteonecrosis of the jaw. Could there be a missing link? Med Oral Patol Oral Cir Bucal. 21. 236
  • Seth, R, Futran, ND, Alam, DS, Knott, PD. (2010). Outcomes of vascularized bone graft reconstruction of the mandible in bisphosphonate-related osteonecrosis of the jaws. Laryngoscope. 120. 2165
  • Wutzl, A, Pohl, S, Sulzbacher, I, Seemann, R, Lauer, G, Ewers, R. (2012). Factors influencing surgical treatment of bisphosphonate-related osteonecrosis of the jaws. Head Neck. 34. 194-200
  • Blus, C, Szmukler-Moncler, S, Giannelli, G, Denotti, G, Orrù, G. (2013). Use of Ultrasonic Bone Surgery (Piezosurgery) to Surgically Treat Bisphosphonate-Related Osteonecrosis of the Jaws (BRONJ). A Case Series Report with at Least 1 Year of Follow-Up. Open Dent J. 7. 94-101
  • Badros, A, Weikel, D, Salama, A, Goloubeva, O, Schneider, A, Rapoport, A. (2006). Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors. J Clin Oncol. 24. 945
  • Markose, G, Mackenzie, FR, Currie, WJ, Hislop, WS. (2009). Bisphosphonate osteonecrosis: a protocol for surgical management. Br J Oral Maxillofac Surg. 47. 294
  • Angiero, F, Sannino, C, Borloni, R, Crippa, R, Benedicenti, S, Romanos, GE. (2009). Osteonecrosis of the jaws caused by bisphosphonates: evaluation of a new therapeutic approach using the Er:YAG laser. Lasers Med Sci. 24. 849
  • Hanasono, MM, Militsakh, ON, Richmon, JD, Rosenthal, EL, Wax, MK. (2013). Mandibulectomy and free flap reconstruction for bisphosphonate-related osteonecrosis of the jaws. JAMA Otolaryngol Head Neck Surg. 139. 1135
  • Schafer, AL, Sellmeyer, DE, Palermo, L, Hietpas, J, Eastell, R, Shoback, DM. (2012). Six months of parathyroid Hormone (1-84) administered concurrently versus sequentially with monthly ibandronate over two years: the PTH and ibandronate combination study (PICS) randomized trial. J Clin Endocrinol Metab. 97. 3522
  • Manfredi, M, Merigo, E, Guidotti, R, Meleti, M, Vescovi, P. (2011). Bisphosphonate-related osteonecrosis of the jaws: a case series of 25 patients affected by osteoporosis. Int J Oral Maxillofac Surg. 40. 277
  • Rugani, P, Acham, S, Kirnbauer, B, Truschnegg, A, Obermayer-Pietsch, B, Jakse, N. (2015). Stage-related treatment concept of medication-related osteonecrosis of the jaw-a case series. Clin Oral Investig. 19. 1329
  • Williamson, RA. (2010). Surgical management of bisphosphonate induced osteonecrosis of the jaws. Int J Oral Maxillofac Surg. 39. 251
  • Junquera, L, Gallego, L, Cuesta, P, Pelaz, A, de Vicente, JC. (2009). Clinical experiences with bisphosphonate-associated osteonecrosis of the jaws: analysis of 21 cases. Am J Otolaryngol. 30. 390
  • Alons, K, Kuijpers, SC, de Jong, E, van Merkesteyn, JP. (2009). Treating low- and medium-potency bisphosphonate-related osteonecrosis of the jaws with a protocol for the treatment of chronic suppurative osteomyelitis: report of 7 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 107. 1-7
  • Saussez, S, Javadian, R, Hupin, C, Magremanne, M, Chantrain, G, Loeb, I. (2009). Bisphosphonate-related osteonecrosis of the jaw and its associated risk factors: a Belgian case series. Laryngoscope. 119. 323
  • Epstein, MS, Wicknick, FW, Epstein, JB, Berenson, JR, Gorsky, M. (2010). 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. 110. 593
  • Vescovi, P, Merigo, E, Meleti, M, Fornaini, C, Nammour, S, Manfredi, M. (2007). Nd:YAG laser biostimulation of bisphosphonate-associated necrosis of the jawbone with and without surgical treatment. Br J Oral Maxillofac Surg. 45. 628
  • Bocanegra-Pérez, S, Vicente-Barrero, M, Knezevic, M, Castellano-Navarro, JM, Rodríguez-Bocanegra, E, Rodríguez-Millares, J. (2012). Use of platelet-rich plasma in the treatment of bisphosphonate-related osteonecrosis of the jaw. Int J Oral Maxillofac Surg. 41. 1410
  • Martins, MA, Martins, MD, Lascala, CA, Curi, MM, Migliorati, CA, Tenis, CA. (2012). Association of laser phototherapy with PRP improves healing of bisphosphonate-related osteonecrosis of the jaws in cancer patients: a preliminary study. Oral Oncol. 48. 79-84
  • Vescovi, P, Merigo, E, Meleti, M, Manfredi, M, Guidotti, R, Nammour, S. (2012). Bisphosphonates-related osteonecrosis of the jaws: a concise review of the literature and a report of a single-centre experience with 151 patients. J Oral Pathol Med. 41. 214
  • Longo, F, Guida, A, Aversa, C, Pavone, E, Di Costanzo, G, Ramaglia, L. (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
  • Pelaz, A, Junquera, L, Gallego, L, García-Consuegra, L, Junquera, S, Gómez, C. (2014). Alternative treatments for oral bisphosphonate-related osteonecrosis of the jaws: a pilot study comparing fibrin rich in growth factors and teriparatide. Med Oral Patol Oral Cir Bucal. 19. 320
  • Freiberger, JJ, Padilla-Burgos, R, Chhoeu, AH, Kraft, KH, Boneta, O, Moon, RE. (2007). Hyperbaric oxygen treatment and bisphosphonate-induced osteonecrosis of the jaw: a case series. J Oral Maxillofac Surg. 65. 1321
  • Stübinger, S, Dissmann, JP, Pinho, NC, Saldamli, B, Seitz, O, Sader, R. (2009). A preliminary report about treatment of bisphosphonate related osteonecrosis of the jaw with Er:YAG laser ablation. Lasers Surg Med. 41. 26-30
  • Ripamonti, CI, Cislaghi, E, Mariani, L, Maniezzo, M. (2011). Efficacy and safety of medical ozone (O(3)) 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 Oncol. 47. 185
  • Curi, MM, Cossolin, GS, Koga, DH, Zardetto, C, Christianini, S, Feher, O. (2011). 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. 69. 2465
  • Atalay, B, Yalcin, S, Emes, Y, Aktas, I, Aybar, B, Issever, H. (2011). Bisphosphonate-related osteonecrosis: laser-assisted surgical treatment or conventional surgery? Lasers Med Sci. 26. 815
  • Mozzati, M, Arata, V, Gallesio, G. (2012). Tooth extraction in patients on zoledronic acid therapy. Oral Oncol. 48. 817
  • Scoletta, M, Arata, V, Arduino, PG, Lerda, E, Chiecchio, A, Gallesio, G. (2013). Tooth extractions in intravenous bisphosphonate-treated patients: a refined protocol. J Oral Maxillofac Surg. 71. 994
  • Rugani, P, Acham, S, Truschnegg, A, Obermayer-Pietsch, B, Jakse, N. (2010). Bisphosphonate-associated osteonecrosis of the jaws: surgical treatment with ErCrYSGG-laser. Case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 110. 1-6
  • Bedogni, A, Saia, G, Bettini, G, Tronchet, A, Totola, A, Bedogni, G. (2011). Long-term outcomes of surgical resection of the jaws in cancer patients with bisphosphonate-related osteonecrosis. Oral Oncol. 47. 420
  • Nocini, PF, Saia, G, Bettini, G, Ragazzo, M, Blandamura, S, Chiarini, L. (2009). Vascularized fibula flap reconstruction of the mandible in bisphosphonate-related osteonecrosis. Eur J Surg Oncol. 35. 373
  • Longobardi, G, Boniello, R, Gasparini, G, Pagano, I, Pelo, S. (2007). Surgical therapy for osteonecotic lesions of the jaws in patients in therapy with bisphosphonates. J Craniofac Surg. 18. 1012
  • Stanton, DC, Balasanian, E. (2009). Outcome of surgical management of bisphosphonate-related osteonecrosis of the jaws: review of 33 surgical cases. J Oral Maxillofac Surg. 67. 943
  • Kos, M, Brusco, D, Kuebler, J, Engelke, W. (2010). Clinical comparison of patients with osteonecrosis of the jaws, with and without a history of bisphosphonates administration. Int J Oral Maxillofac Surg. 39. 1097
  • Hoefert, S, Eufinger, H. (2011). Relevance of a prolonged preoperative antibiotic regime in the treatment of bisphosphonate-related osteonecrosis of the jaw. J Oral Maxillofac Surg. 69. 362
  • Vescovi, P, Campisi, G, Fusco, V, Mergoni, G, Manfredi, M, Merigo, E. (2011). Surgery-triggered and non surgery-triggered Bisphosphonate-related Osteonecrosis of the Jaws (BRONJ): A retrospective analysis of 567 cases in an Italian multicenter study. Oral Oncol. 47. 191
  • Jabbour, Z, El-Hakim, M, Mesbah-Ardakani, P, Henderson, JE, Albuquerque R, Jr. (2012). The outcomes of conservative and surgical treatment of stage 2 bisphosphonate-related osteonecrosis of the jaws: a case series. Int J Oral Maxillofac Surg. 41. 1404
  • Ferlito, S, Puzzo, S, Palermo, F, Verzì, P. (2012). Treatment of bisphosphonate-related osteonecrosis of the jaws: presentation of a protocol and an observational longitudinal study of an Italian series of cases. Br J Oral Maxillofac Surg. 50. 425
  • Schubert, M, Klatte, I, Linek, W, Müller, B, Döring, K, Eckelt, U. (2012). The saxon bisphosphonate register - therapy and prevention of bisphosphonate-related osteonecrosis of the jaws. Oral Oncol. 48. 349
  • Beninati, F, Pruneti, R, Ficarra, G. (2013). Bisphosphonate-related osteonecrosis of the jaws (Bronj). Med Oral Patol Oral Cir Bucal. 18. 752
  • Holzinger, D, Seemann, R, Klug, C, Ewers, R, Millesi, G, Baumann, A. (2013). Long-term success of surgery in bisphosphonate-related osteonecrosis of the jaws (BRONJs). Oral Oncol. 49. 66-70
  • Anavi-Lev, K, Anavi, Y, Chaushu, G, Alon, DM, Gal, G, Kaplan, I. (2013). Bisphosphonate related osteonecrosis of the jaws: clinico-pathological investigation and histomorphometric analysis. Oral Surg Oral Med Oral Pathol Oral Radiol. 115. 660
  • Van den Wyngaert, T, Claeys, T, Huizing, MT, Vermorken, JB, Fossion, E. (2009). Initial experience with conservative treatment in cancer patients with osteonecrosis of the jaw (ONJ) and predictors of outcome. Ann Oncol. 20. 331
  • Stockmann, P, Vairaktaris, E, Wehrhan, F, Seiss, M, Schwarz, S, Spriewald, B. (2010). Osteotomy and primary wound closure in bisphosphonate-associated osteonecrosis of the jaw: a prospective clinical study with 12 months follow-up. Support Care Cancer. 18. 449
  • Ferlito, S, Puzzo, S, Liardo, C. (2011). Preventive protocol for tooth extractions in patients treated with zoledronate: a case series. J Oral Maxillofac Surg. 69. 1-4
  • Thumbigere-Math, V, Tu, L, Huckabay, S, Dudek, AZ, Lunos, S, Basi, DL. (2012). A retrospective study evaluating frequency and risk factors of osteonecrosis of the jaw in 576 cancer patients receiving intravenous bisphosphonates. Am J Clin Oncol. 35. 386
  • Melea, PI, Melakopoulos, I, Kastritis, E, Tesseromatis, C, Margaritis, V, Dimopoulos, MA. (2014). Conservative treatment of bisphosphonate-related osteonecrosis of the jaw in multiple myeloma patients. Int J Dent. 2014. 427273