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Rev Clin Periodoncia Implantol Rehabil Oral.2008;1:32-37
REVISIÓN BIBLIOGRÁFICA [PDF]

Osteonecrosis de los Maxilares Asociado a Terapia con Bifosfonatos: Situación Actual

Bisphosphonate Therapy-Associated Osteonecrosis of the Jaws: Current Situation

Cisterna C 1 , Yanine N 2 , González C 3 Villanueva J. 4

1Cirujano-Dentista, Universidad de Chile. Chile.
2Cirujano-Dentista. Departamento de Cirugía y Traumatología Máxilo Facial, Universidad de Chile. Chile.
3Cirujano-Dentista. Clínica integral del adulto, Universidad de Chile. Chile.
4Cirujano máxilo facial. Departamento de Cirugía y Traumatología Máxilo Facial Universidad de Chile. Chile.

Resumen

En los últimos años, debido a distintas causas, un creciente número de pacientes se encuentra bajo tratamiento médico con bifosfonatos. Se ha descrito que estos fármacos podrían estar asociados con la aparición de ulceraciones intraorales espontáneas y osteonecrosis de los huesos maxilares. El propósito de esta revisión bibliográfica es describir las características de los bisfosfonatos, su mecanismo de acción, las manifestaciones clínicas de la osteonecrosis de los maxilares, su manejo terapéutico y pautas de prevención. Los resultados indican, que los pacientes en mayor riesgo de desarrollar osteonecrosis de los maxilares son aquellos que reciben terapia con bifosfonatos nitrogenados intravenosos. Sobre el 70% de los casos se produce después de un procedimiento dental quirúrgico. La mandíbula es más comúnmente afectada que el maxilar. Se propone que el origen del cuadro se debe a la baja tasa de recambio óseo y disminuida vascularización que generan los bifosfonatos, lo que conlleva una disminución en la capacidad de cicatrización y regeneración de los tejidos. El manejo de las lesiones es de alta complejidad. Generalmente, se recomienda un tratamiento paliativo con antisépticos orales y antibioterapia. El debridamiento del hueso necrótico se indica en casos severos. Concluimos que es imprescindible conocer esta complicación para un temprano diagnóstico y tratamiento de ella, así como, prevenir su aparición. En este sentido, es recomendable realizar un examen dental, procurando diagnosticar y eventualmente eliminar todo sitio susceptible de infección antes del inicio de una terapia con bifosfonatos. Además, evitar procedimientos quirúrgicos, en pacientes en riesgo de desarrollar la complicación.

Palabras clave: osteonecrosis, bifosfonatos, osteonecrosis de los maxilares.

Abstract

In recent years, due to different causes, an increasing number of patients are under medical treatment with bisphosphonates. These drugs might be associated with the growing of spontaneous ulceration of the oral mucosa and osteonecrosis of the jaws. The purpose of this review is to describe the characteristics of bisphosphonates, its mechanism of action, clinical manifestation of osteonecrosis of the jaws, therapeutic management and prevention. Patients treated with intravenous nitrogen-containing bisphosphonates, have a major risk to develop osteonecrosis. Over 70% of the cases are preceded by a dental surgical procedure. The mandible is more commonly affected than the maxilla. Probably the origin of the osteonecrosis of the jaws is a decreased microcirculation and a limited bone turnover due to bisphosphonates, leading to diminish their healing capacity and regeneration of the tissues. The management of the lesions is difficult. Palliative treatment is proposed with oral rinses and systemic antibiotic therapy. Removal of necrotic bone is recommended in severe cases. In conclusion, is necessary to know this condition for an early diagnosis and treatment, so to prevent its apparition. In this way, it is recommendable to do an oral examination and diagnosis, to treat active oral infections and eliminate sites at high risk for infection before getting the bisphosphonate therapy started. Furthermore, to avoid surgical procedures in risky patients.

Key words: Key words: osteonecrosis, bisphosphonates, osteonecrosis of the jaws.

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Bibliografía

1.
J. Wade
Rheumathology: 15 Ostoporosis
CMAJ, 165 (2001), pp. 45-50
2.
C. Gridelli
The use of bisphosphonates in elderly cancer patients
Oncologist, 12 (2007), pp. 62-71 http://dx.doi.org/10.1634/theoncologist.12-1-62
3.
D. Lam,G. Sándor,H. Holmes,W. Evans,C. Clokie
A review of Bisphosphonate-associated osteonecrosis of the jaws and its management
JCDA, 73 (2007), pp. 417-422
4.
E. Stoopler,D. Volg
Stadtmauer. Medical management update: Multiple myeloma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 103 (2007), pp. 599-609
5.
R. Marx
Pamidronate (Aredia) and Zolendronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic
J Oral Maxillofac Surg, 61 (2003), pp. 1115-1116
6.
C. Migliorati
Bisphosphonates and oral cavity avascular bone necrosis
J Clin Oncol, 21 (2003), pp. 4253-4254 http://dx.doi.org/10.1200/JCO.2003.99.141
7.
S. Ruggiero,B. Mebrota,T. Rosenberg,S. Engroff
Osteonecrosis of the jaws associated with the use of Bisphosphonates: A review of 63 cases
J Oral Maxillofac Surg, 62 (2004), pp. 527-534
8.
J. Bagan,J. Murillo,Y. Jiménez
Avascular jaw Osteonecrosis in association with cancer chemotherapy: series of 10 cases
J Oral Pathol Med, 34 (2005), pp. 120-123 http://dx.doi.org/10.1111/j.1600-0714.2004.00269.x
9.
I. Dimitrakoupoulos,C. Magoupolos,D. Karakasis
Bisphosphonate-induced avascular osteonecrosis of the jaws: a clinical report of the 11 cases
Int J Oral Maxillofac Surg, 35 (2006), pp. 588-593 http://dx.doi.org/10.1016/j.ijom.2006.02.022
10.
C. Fernandes,R. Souza,F. Lancas
Bisfosfonatos: Síntese Análises químicas e aplicoes farmacológicas
Quim Nova, 28 (2005), pp. 274-280
11.
S. Luckman,F. Coxon,F. Ebetino,R. Russel,M. Rogers
Heterocycle-containing bisphosphonates cause apoptosis and inhibit bone reorption by preventing protein prenylation: evidence from structure-activity relationships in J774 macrophages
J Bone Miner Res, 13 (1998), pp. 1668-1678 http://dx.doi.org/10.1359/jbmr.1998.13.11.1668
12.
Gutta Rajesh,Louis Patrick
Bisphosphonates and osteonecrosis of the jaws: Science and rationale
Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 104 (2007), pp. 186-193 http://dx.doi.org/10.1016/j.tripleo.2006.12.004
13.
Joan Otomo-Corgel
Implants and oral bisphosphonates: risky business?
J Periodontol, 78 (2007), pp. 373-376 http://dx.doi.org/10.1902/jop.2007.073001
14.
R. Marx,Y. Sawatari,M. Fertin,V. Broumand
Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention and treatment
J Oral Maxillofac Surg, 63 (2005), pp. 1567-1575 http://dx.doi.org/10.1016/j.joms.2005.07.010
15.
G. Ficarra,F. Beninati,I. Rubino,A. Vannuchi,G. Longo,P. Tonelli,G. Pini Prato
Osteonecrosis of the jaws in periodontal patients with a history of bisphosphonates treatment
J Clin Periodontol, 32 (2005), pp. 1123-1128 http://dx.doi.org/10.1111/j.1600-051X.2005.00842.x
16.
J. Wood,K. Bonjean,S. Ruetz
Novel antiogenic effects of the bisphosphonate compound Zoledronic acid
JPET, 302 (2002), pp. 1055-1061
17.
Allegra A, Oteri G, Nastro E, y cols. Patients with bisphosphonates-associated osteonecrosis of the jaw have reduced circulating endothelial cells. Hematol Oncol 2007 (en prensa)
18.
Fleisch Herbert
Bisphosphonates: Mechanisms of action
Endocrine Reviews, 19 (1998), pp. 80-100 http://dx.doi.org/10.1210/edrv.19.1.0325
19.
H.L. Wang,D. Weber,L. McCauley
Effect of long–term oral bisphosphonates on implant wound healing: literature review and a case report
J Periodontol, 78 (2007), pp. 584-594 http://dx.doi.org/10.1902/jop.2007.060239
20.
S. Luckman,D. Hughes,F. Coxon,R. Russell,M. Rogers
Nitrogen-containing bisphosphonates inhibit the Mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras
J Bone Miner Res, 13 (1998), pp. 581-589 http://dx.doi.org/10.1359/jbmr.1998.13.4.581
21.
T. Anguita,J. Agurto,I. Roa,G. Laissle
Osteonecrosis associated with the use of biphosphonates: Case report
Rev Med Chile, 134 (2006), pp. 1161-1170 http://dx.doi.org//S0034-98872006000900011
22.
C. Migliorati,J. Casiglia,J. Epstein,P. Jacobsen,M. Siegel,S. Woo
Managing the care of patients with bisphosphonate-associated osteonecrosis: an American Academy of Oral Medicine position paper
J Am Dent Assoc, 136 (2005), pp. 1658-1660
23.
T. Mavrokokki,A. Cheng,B. Stein,A. Goss
Nature and frequency of bisphosphonateassociated osteonecrosis of the jaws in Australia
J Oral Maxillofac Surg, 65 (2007), pp. 415-423 http://dx.doi.org/10.1016/j.joms.2006.10.061
24.
A. Leite,P. Figueiredo,N. Melo
Bisphosphonate-associated osteonecrosis of the jaws Report of a case and literature review
Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 102 (2006), pp. 14-21 http://dx.doi.org/10.1016/j.tripleo.2005.10.045
25.
P. Fugazzotto,W. Lightfoot,R. Jaffin,A. Kumar
Implant placement with or without simultaneous tooth extraction in patients taking oral bisphosphonates: postoperative healing, early follow-up, and the incidence of complications in two private practices
J Periodontol, 78 (2007), pp. 1664-1670 http://dx.doi.org/10.1902/jop.2007.060514
26.
R. Marx
Oral and intravenous bisphosphonates induced osteonecrosis of the jaws History, etiology, prevention and treatment
Quintessence Publishing Co Inc, (2007), pp. 9-96
27.
B. Durie,M. Katz,J. Crowley
Osteonecrosis of the jaw and bisphosphonates
N Engl J Med, 353 (2005), pp. 99-102
28.
A. Bamias,E. Kastritis,C. Bamia
Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors
J Clin Oncol, 23 (2005), pp. 8580-8590 http://dx.doi.org/10.1200/JCO.2005.02.8670
29.
B.N. Landis,I. Dojcinovic,M. Richter,M. Hugentobler
Osteonecrosis of the jaws: maxillofacial recommendations for bisphosphonate prescribers
J Intern Med, 261 (2007), pp. 101-102 http://dx.doi.org/10.1111/j.1365-2796.2006.01747.x
30.
M.R. Markiewicz,J.E. Margarone 3rd,J.H. Campbell,A. Aguirre
Bisphosphonate-associated osteonecrosis of the jaws: a review of current knowledge
J Am Dent Assoc, 136 (2005), pp. 1669-1670
31.
D. Pastor-Zuazaga,J. Garatea-Crelgo,R. Martino-Gorbea,A. Etayo-Pérez,C. Sebastián- López
Osteonecrosis of the jaws and bisphosphonates Report of three cases
Med Oral Patol Oral Cir Bucal, 11 (2006), pp. 76-79
32.
R. Marx
Int J Oral Maxillofac Implants, 22 (2007), pp. 149-151
33.
K. Soileau
Oral post-surgical complications following the administration of bisphosphonates given for osteopenia related to malignancy
J Periodontol, 77 (2006), pp. 738-743 http://dx.doi.org/10.1902/jop.2006.050187
34.
E. Braun,V. Iacono
Bisphosphonates: case report of nonsurgical periodontal therapy and osteochemonecrosis
Int J Periodontics Restorative Dent, 26 (2006), pp. 315-319
35.
M. Jeffcoat
Safety of oral bisphosphonates: controlled studies on alveolar bone
Int J Oral Maxillofac Implants, 21 (2006), pp. 349-353
36.
D.J. Rinchuse,D. Rinchuse,M. Sosovicka,J. Robinson,R. Pendleton
Orthodontic treatment of patients using bisphosphonates: A report of 2 cases
Am J Orthod Dentofacial Orthop, 131 (2007), pp. 321-326 http://dx.doi.org/10.1016/j.ajodo.2006.11.002
37.
A. Sarathy,S.L. Bourgeois Jr.,G. Goodell
Bisphosphonate-associated osteonecrosis of the jaws and endodontic treatment: two case reports
J Endod, 31 (2005), pp. 759-763
38.
H. Katz
Endodontic implications of bisphosphonate-associated osteonecrosis of the jaws: a report of three cases
J Endod, 31 (2005), pp. 831-834
39.
S.B. Woo,K. Hande,P.G. Richardson
N Eng J Med, 353 (2005), pp. 100
40.
M. Khamaisi,E. Regev,N. Yarom,B. Avni,E. Leitersdorf
Posible association between diabetes and bisphosphonate-related jaw osteonecrosis
J Clin Endocrinol Metab, 92 (2007), pp. 1172-1180 http://dx.doi.org/10.1210/jc.2006-2036
41.
N. Lane,G.C. Armitage,P. Loomer
Bisphosphonate therapy improves the outcome of conventional periodontal treatment: results of a 12-month, randomized, placebocontrolled study
J Periodontol, 76 (2005), pp. 1113-1120 http://dx.doi.org/10.1902/jop.2005.76.7.1113
42.
J. Goya,H. Paez,P. Mandalunis
Effect of topical administration of monosodium olpadronate on experimental periodontitis in rats
J Periodontol, 77 (2006), pp. 1-6 http://dx.doi.org/10.1902/jop.2006.77.1.1
43.
C. Eberhardt,habermann,S. Muller,M. Schwarz,F. Bauss,A. Kurth
The bisphosphonate ibandronate accelerates osseointegration of hydroxyapatite-coated cementless implants in an animal model
J Orthop Sci, 12 (2007), pp. 61-66 http://dx.doi.org/10.1007/s00776-006-1081-2
44.
H. Kajiwara,T. Yamaza,M. Yoshinari
The bisphosphonate pamidronate on the surface of titanium stimulates bone formation around tibial implants in rats
Biomaterials, 26 (2005), pp. 581-587 http://dx.doi.org/10.1016/j.biomaterials.2004.02.072
45.
B. Houshmand,H. Rahimi,F. Ghanavati,A. Alisard,B. Eslami
Boosting effect of bisphosphonates on osteoconductive materials: a histologic in vivo evaluation
J Periodont Res, 42 (2007), pp. 119-123 http://dx.doi.org/10.1111/j.1600-0765.2006.00923.x

 

Trabajo recibido el 04/10/2007.
Aprobado para su publicación el 15/01/2008.

CORRESPONDENCIA AUTOR
Carlos Cisterna Vergara
Facultad de Odontología, Universidad de Chile
Olivos 943. Independencia. Santiago.
ccisterna@odontologia.uchile.cl

Copyright © 2008.
Sociedad de Periodoncia de Chile, Sociedad de Implantología Oral de Chile y Sociedad de Prótesis y Rehabilitación Oral de Chile.