Estudio experimental para la valoración de la cicatrización ósea con Ácido Zoledrónico en ratas Wistar

  1. C. Moñivas Palomero
  2. P. García López
  3. P. Arias Sanz
  4. A. Izquierdo Hernández
  5. C. López Carrizosa
  6. D. Guijarro Sánchez
Revista:
Sanidad militar: revista de sanidad de las Fuerzas Armadas de España

ISSN: 1887-8571

Año de publicación: 2015

Volumen: 71

Número: 4

Páginas: 232-238

Tipo: Artículo

DOI: 10.4321/S1887-85712015000400003 DIALNET GOOGLE SCHOLAR

Otras publicaciones en: Sanidad militar: revista de sanidad de las Fuerzas Armadas de España

Resumen

Antecedentes y objetivos: El aumento del consumo de bifosfonatos en la sociedad actual, puede incrementar el riesgo de osteonecrosis mandibular. Se realizó este estudio para valorar si tras la extracción dentaria, después de la administración subcutánea de ácido zoledrónico 7,5µg/Kg o 35 µg/Kg (Zometa®) en ratas Wistar, aparecen signos clínicos, radiográficos e histopatológicos de osteonecrosis y/o inflamación. Lugar de realización: Centro Experimentación Animal del Hospital de Defensa. Material y Métodos: Estudio experimental, in vitro, randomizado, intervencionista. Se utilizaron un total de 30 ratas Wistar (adultas, sanas), repartiéndolas en tres grupos de 10 animales, según sexo, grupo y fármaco: G0: Sin tratamiento con ácido zoledrónico. G1: Con tratamiento de ácido zoledrónico 7,5µg/Kg subcutáneo una dosis en los días 1, 15 y 30. G2: Con tratamiento de ácido zoledrónico 35µg/Kg subcutáneo una dosis en los días 1, 15 y 30. En todos los grupos se realizó exodoncia del primer molar inferior derecho el día 30, sacrificando los animales a las cuatro semanas postextracción, observando clínica, histológica y radiográficamente la aparición de osteonecrosis e inflamación. Resultados: Clínicamente se observaron en un 26,6% falta de epitelización compatible con signos precoces de osteonecrosis mandibular, según criterios de la American Association of Oral Maxillofacial Súrgeons (AAOMS). Esta es dosis dependiente en 3 animales de G1 (10%) y 5 animales de G2 (16,6%). Los resultados presentaron significación estadística p<0,011. Ausencia histológica y radiológica de osteonecrosis p< 0,001 e inflamación p <0,001 en todos los grupos. Conclusiones: La administración subcutánea de 7,5µg/Kg o 35µg/Kg de ácido zoledrónico durante cuatro semanas, tras la realización de una extracción dentaria, no da lugar a signos histopatológicos de osteonecrosis e inflamación (p<0,001) pero si a alteraciones clínicas dosis dependientes (p<0,011) compatibles con estadios iniciales de osteonecrosis mandibular según criterios de la AAOMS.

Referencias bibliográficas

  • Rogers, MJ, Gordon, S, Benford, HL, Coxon, FP, Luckman, SP, Monkkonen, J. (2000). Cellular and molecular mechanisms of action of bisphosphonates. Cancer. 86. 2961
  • Wood, J, Bonjean, K, Ruetz, S, Bellahcéne, A, Devy, L, Foidart, JM. (2002). Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther. 302. 1055
  • Fournier, P, Boissier, S, Filleur, S, Guglielmi, J, Cabon, F, Colombel, M. (2002). Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. Cancer Res.. 62. 6538
  • Liccata, AA. (2005). Discovery, clinical development, and therapeutic uses of biphosphonates. Ann Pharmacother.. 39. 668
  • Coleman, RE. (2002). Future directions in the treatment and prevention of bone metastases. Am J Clin Oncol.. 25. 32
  • Melo, MD, Obeid, G. (2005). Osteonecrosis of the jaws in patients with a history of receiving bisphosphonate therapy: strategies for prevention and early recognition. J Am Dent Assoc.. 136. 1675
  • Drake, MT, Clarke, BL, Khosla, S. (2008). Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc.. 83. 1032
  • Woo, SB, Hellstein, JW, Kalmar, JR. (2006). Systematic Review: Biphosphonates and Osteonecrosis of the Jaws. Ann Intern Med.. 144. 753-761
  • Fleisch, H. (1998). Bisphosphonates: Mechanisms of Action. Endocrine Reviews. 19. 80-100
  • Arrabal Martín, M, Valle Díaz de la Guardia, F, Jiménez Pacheco, A, López León, V, Arrabal Polo, MA, Zuluaga Gómez, A. (2007). Tratamiento de la litiasis renal con bifosfonatos. Arch Esp Urol.. 60. 745
  • Marx, RE. (2003). Pamindronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg.. 61. 1115
  • Ruggiero, SL, Mehrotra, B, Rosenberg, TJ, Engroff, SL. (2004). Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg.. 62. 527
  • Senel, FC, Kadioglu, Duman M, Muci, E, Cankaya, M, Pampu, AA, Ersoz, S, Gunhan, O. (2010). Jaw bone changes in rats after treatment with zoledronate and pamidronate. Oral Surg Oral Med Oral Pathol Oral Radiol Endod.. 109. 385
  • Roelofs, AJ, Thompson, K, Gordon, S, Rogers, MJ. (2006). Molecular mechanisms of action of bisphosphonates: current status. Clin Cancer Res.. 12.
  • Pazianas, M, Miller, P, Blumentals, WA. (2007). A review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics. Clin Ther.. 29. 1548
  • Allgrove, Jeremy. (1997). Biphosphonates. Archives of Disease in Childhood. 76. 73-75
  • Migliorati, CA, Casiglia, J. (2005). Managing the care of patients with bisphosphonate-associated osteonecrosis. J Am Dent Assoc.. 136. 1658
  • Migliorati, CA. (2003). Biphosphonates and oral cavitynavascular necrosis of bone. J Clin Oncol. 21. 4253
  • 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
  • Estilo, CL, Van Poznak, CH, Wiliams, T, Bohle, GC, Lwin, PT, Zhou, Q. (2008). Osteonecrosis of the maxilla and mandible in patients with advanced cancer treated with bisphosphonate therapy. Oncologist. 13. 911
  • Favia, G, Pilolli, GP, Maiorano, E. (2009). Histologic and histomorphometric features of bisphosphonate-related osteonecrosis of the jaws: an analysis of 31 cases with confocal laser scanning microscopy. Bone. 45. 406
  • Escobar López, EA, López López, J, Marques Soares, MS, Chimenos Küstner, E. (2007). Osteonecrosis de los maxilares asociada a bifosfonatos: revisión sistemática. Av. Odontoestomatol. 23. 91-101
  • Dixon, RB, Tricker, ND, Garetto, LP. (1997). Bone turnover in elderly canine mandible and tibia. J Dent Res. 76.
  • Marx, RE, Sawatari, Y, Fortin, M, Broumand, V. (2005). Biphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg. 63. 1567
  • Badros, A, Weikel, D, Salama, A, Goloubeva, O, Schneider, A, Rapoport, A, Fenton, R, Gahres, N, Sausville, E, Ord, R, Meiller, T. (2006). Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors. J Clin Oncol.. 24. 945
  • Jiménez Soriano, Y, Bagan, JV. (2005). Los bifosfonatos, nueva causa de osteonecrosis maxilar por fármacos: situación actual. Med Oral Patol Oral Cir Bucal. 10. 88-91
  • Hoff, AO, Toth, BB, Altundag, K, Guarneri, V, Adamus, A, Nooka, AK. (2006). Osteonecrosis of the jaw in patients receiving intravenous bisphosphonate therapy. J Clin Oncol.. 24.
  • Reid, I. R., Cornish, J.. (2012). Nat. Rev. Rheumatol.. 8. 90
  • Expert Panel Recommendations for the Prevention, Diagnosis, and Treatment of Osteonecrosis of the Jaws. Novartis. East Hanover^eNJ NJ.
  • Migliorati, CA, Casiglia, J, Epstein, J, Jacobsen, PL, Siegel, MA, Woo, SB. (2005). Managing the care of patients with bisphosphonate-associated osteonecrosis. Journal American Dental Association. 136. 1658
  • (2007). American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg. 65. 369
  • Aragonès Forès, R, Orozco López, P. (2002). Abordaje de la osteoporosis en la atención primaria en España (estudio ABOPAP-2000). Aten Primaria. 30. 350
  • Atchley, W, Fitch, W. (1991). Genes trees and the origins of inbread strain of mice. Science. 254. 554
  • Clause, BT. (1998). The Wistar Intitute Archives: Rats (Not Mice) and History. Mendel Newsl.. 7. 2-7
  • Gottardello, KZ, Rogério da Silva, J, Jacks, J. (2007). A new method for extraction of mandibular first molars in rats. Braz J Oral Sci. 6. 1344
  • Vignery, A, Baron, R. (1980). Dynamic histomorphometry of alveolar bone remodeling in the adult rat. Anat Rec.. 96. 191-200
  • Mehmet, A.E, Abdulkadir, B.C, Sabri, C.I, Sabit, D, Merva, S, Cetin, K. (2011). Extraction socket healing in rats treated with bisphosphonate: Animal model for bisphosphonate related osteonecrosis of jaws in multiple myeloma patientes. Med oral patol Oral Cir Bucal. 16. 879
  • Marino, KL, Zakhary, I, Abdelsayed, RA, Carter, JA, O´Neill, JC, Khashaba, RM. (2012). Development of a rat model of bisphosphonate-related osteonecrosis of the jaw (BRONJ). J Oral Implantol.. 38. 511
  • Sonis, ST, Watkins, BA, Lyng, GD, Lerman, MA, Anderson, KC. (2009). Bony changes in the jaws of rats treated with zoledronic acid and dexamethasone before dental extractions mimic bisphosphonate-related osteonecrosis in cancer patients. Oral Oncol.. 45. 164
  • 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.
  • Agaçayak, KS, Yuksel, H, Atilgan, S, Koparal, M, Uçan, MC, Özgöz, M. (2014). Experimental investigation of relationship between trauma and bisphosphonate-related osteonecrosis. Níger J Clin Pract.. 17. 559
  • Johansen, JR. (1970). Repair of the post-extaccion alveolus in the Wistar rat: A histologic and autoradiographic study. Acta Odontolol Scand.. 28. 441-6179
  • Pietrokovski, J, Massler, M. (1967). Ridge remodeling after tooth extraction in rats. J Dent Res.. 46. 222
  • Kuroshima, S, Mecano, RB, Tanoue, R, Koi, K, Yamashita, J. (2014). Distinctive tooth-extraction socket healing: bisphosphonate versus parathyroid hormone therapy. J Periodontol. 85. 24-33
  • Hokugo, A, Christensen, R, Chung, EM, Sung, EC, Felsenfeld, AL, Sayre, JW. (2010). Increased Prevalence of Bisphosphonate-Related Osteonecrosis of the Jaw with Vitamin D Deficiency in Rats. Journal of Bone and Mineral Research. 25. 1337
  • Biasotto, M, Chiandussi, S, Zacchigna, S, Moimas, S, Dore, F, Pozzato, G. (2010). A novel animal model to study non-spontaneous bisphosphonates osteonecrosis of jaw. J Oral Pathol Med. 39. 390
  • Marino, KL, Zakhary, I, Abdelsayed, RA, Carter, JA, O´Neill, JC, Khashaba, RM, Elsalanty, M, Stevens, MR, Borke, JL. (2012). Development of a rat model of bisphosphonate-related osteonecrosis of the jaw (BRONJ). J Oral Implantol.. 38. 511
  • Reid, IR, Bolland, MJ, Grey, AB. (2007). Is bisphosphonate-associated osteonecrosis of the jaw caused by soft tissue toxicity?. Bone. 41. 318
  • Conte Neto, N, Spolidorio, LC, Andrade, CR, Bastos, AS, Guimaraes, M, Marcantonio, E Jr. (2013). Experimental development of biphosphonate-related osteonecrosis of the jaws in rodents. Int J Exp Path.. 94. 65-73
  • Abtahi, J, Agholme, F, Sandberg, O, Aspenberg, P. (2012). Bisphosphonate-induced osteonecrosis of the jaw in a rat model arises first after the bone has become exposed: no primary necrosis in unexposed bone. J Oral Pathol Med. 41. 494
Fuente de los datos: Dialnet