Οστεονέκρωση των γνάθων από διφωσφονικά: ανασκόπηση των νεώτερων δεδομένων και προτεινόμενα πρωτόκολλα αντιμετώπισης βασισμένα σε τεκμηρίωση
Αθανάσιος ΚΥΡΓΙΔΗΣ1, Κωνσταντίνος ΑΝΤΩΝΙΑΔΗΣ2
Κλινική Στοματικής και Γναθοπροσωπικής Χειρουργικής. Οδοντιατρική Σχολή Αριστοτελείου Πανεπιστημίου
Θεσσαλονίκης
(Διευθυντής: Καθηγητής Ν. Λαζαρίδης)
Αρχεία Ελληνικής Στοματικής και Γναθοπροσωπικής Χειρουργικής (2009) 1, 3-14
ΠΕΡΙΛΗΨΗ: Η οστεονέκρωση των γνάθων από διφωσφονικά είναι μια κλινική οντότητα που εμφα-
νίστηκε το 2003 και έκτοτε απασχολεί τον ιατρικό κόσμο. Οι περισσότερες από τις περιπτώσεις ανα-
πτύσσονται σε ασθενείς με πολλαπλό μυέλωμα ή μεταστατικό καρκίνο που λαμβάνουν ενδοφλέβια
αγωγή με διφωσφονικά, αν και έχει περιγραφεί επίσης σε οστεοπορωτικές γυναίκες που αντιμετω-
πίζονται με από του στόματος αγωγή. Στην παρούσα μελέτη γίνεται συστηματική ανασκόπηση της
βιβλιογραφίας για μελέτες που αφορούν την πρόληψη και αντιμετώπιση της νόσου. Προτείνονται
συγκεκριμένα θεραπευτικά πρωτόκολλα αντιμετώπισης της νόσου και περίθαλψης των ασθενών.
Ιδιαίτερη μνεία γίνεται σε νεώτερες διεθνείς μελέτες που αλλάζουν τα μέχρι σήμερα δεδομένα ανα-
φορικά με την πρόληψη και την αντιμετώπιση της νόσου. Ο τακτικός προληπτικός οδοντοστοματο-
λογικός έλεγχος είναι απαραίτητο να εφαρμόζεται πριν και κατά τη διάρκεια της αγωγής με τα σκευ-
άσματα αυτά. Οι ιατροί που χορηγούν διφωσφονικά οφείλουν να ενημερώνουν τον ασθενή τους για
το ενδεχόμενο ανάπτυξης της επιπλοκής και να τον παραπέμπουν στον οδοντίατρο. Χειρουργικές
πράξεις σε ασθενείς που λαμβάνουν διφωσφονικά ενδοφλεβίως σκόπιμο είναι να γίνονται μόνο από
εξοικειωμένους με την επιπλοκή. Στους ασθενείς που νοσούν από οστεονέκρωση η θεραπεία πρέ-
πει να είναι καταρχήν συντηρητική και εφόσον η βλάβη δεν υποχωρεί, οφείλουν να εξεταστούν και
άλλες θεραπευτικές εναλλακτικές λύσεις. Η αντιμετώπιση της επιπλοκής στους ασθενείς αυτούς επι-
βάλλεται να γίνεται από στοματικό και γναθοπροσωπικό χειρουργό.
ΛΕΞΕΙΣ ΚΛΕΙΔΙΑ: Oστεονέκρωση, Oστεομυελίτιδα, Διφωσφονικά, Πρόληψη, Θεραπεία
REFERENCES
Albandar JM: Oral bisphosphonate therapy may not significantly
compromise dental implants success. J Evid Based
Dent Pract 8:229-231, 2008
ASCO (2007) ASCO/NCCN Quality Measures: Breast
and Colorectal Cancers, April 2007 UPDATE.
Bagan JV, Jimenez Y, Diaz JM, Murillo J, Sanchis JM, Poveda
R, et al.: Osteonecrosis of the jaws in intravenous bisphosphonate
use: Proposal for a modification of the
clinical classification. Oral Oncol:In Press, 2008
Bagan JV, Jimenez Y, Murillo J, Hernandez S, Poveda R,
Sanchis JM, et al.: Jaw osteonecrosis associated with
bisphosphonates: multiple exposed areas and its relationship
to teeth extractions. Study of 20 cases. Oral
Oncol 42:327-329, 2006
Bagan JV, Murillo J, Jimenez Y, Poveda R, Milian MA,
Sanchis JM, et al.: Avascular jaw osteonecrosis in association
with cancer chemotherapy: series of 10 cases. J
Oral Pathol Med 34:120-123, 2005
Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos
I, Bozas G, et al.: Osteonecrosis of the jaw in
cancer after treatment with bisphosphonates: incidence
and risk factors. JClinOncol 23:8580-8587, 2005
Bell BM, Bell RE: Oral bisphosphonates and dental implants:
a retrospective study. J Oral Maxillofac Surg 66:
1022-1024, 2008
Body JJ, Coleman RE, Piccart M: Use of bisphosphonates in
cancer patients. Cancer TreatRev 22:265-287, 1996
Brufsky AM: Zoledronic acid for cancer therapy-induced
and postmenopausal bone loss. Expert Opin Pharmacother
9:1013-1028, 2008
Coleman RE: Clinical features of metastatic bone disease
and risk of skeletal morbidity. ClinCancer Res 12:
6243s-6249s, 2006a
Coleman RE: The role of bone markers in metastatic bone
disease. Cancer TreatRev 32 Suppl 1:1-2.:1-2, 2006b
Coleman RE: Risks and benefits of bisphosphonates. Br J
Cancer 98:1736-1740, 2008
Dimopoulos MA, Kastritis E, Anagnostopoulos A, Melakopoulos
I, Gika D, Moulopoulos LA, et al.: Osteonecrosis
of the jaw in patients with multiple myeloma
treated with bisphosphonates: evidence of increased
risk after treatment with zoledronic acid. Haematologica 91:968-971, 2006
Farrugia MC, Summerlin DJ, Krowiak E, Huntley T,
Freeman S, Borrowdale R, et al.: Osteonecrosis of the
mandible or maxilla associated with the use of new generation
bisphosphonates. Laryngoscope 116:115-
120, 2006
Generali D, Dovio A, Tampellini M, Tucci M, Tedoldi S,
Torta M, et al.: Changes of bone turnover markers and
serum PTH after night or morning administration of
zoledronic acid in breast cancer patients with bone
metastases. Br J Cancer 98:1753-1758, 2008
Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G,
Travers R: Cyclic administration of pamidronate in
children with severe osteogenesis imperfecta. N Engl J
Med 339:947-952, 1998
Gomez Font R, Martinez Garcia ML, Olmos Martinez JM:
Osteochemonecrosis of the jaws due to bisphosphonate
treatments. Update. Med Oral Patol Oral Cir
Bucal 13:E318-324, 2008
Hansen T, Kunkel M, Weber A, James Kirkpatrick C: Osteonecrosis
of the jaws in patients treated with bisphosphonates
- histomorphologic analysis in comparison
with infected osteoradionecrosis. J Oral Pathol
Med 35:155-160, 2006
Hashimoto K, Morishige K, Sawada K, Tahara M, Shimizu S,
Ogata S, et al.: Alendronate suppresses tumor angiogenesis
by inhibiting Rho activation of endothelial cells.
Biochem Biophys Res Commun 354:478-484, 2007
Hess LM, Jeter JM, Benham-Hutchins M, Alberts DS:
Factors associated with osteonecrosis of the jaw
among bisphosphonate users. Am J Med 121:475-483
e473, 2008
Jakobsen T, Baas J, Kold S, Bechtold JE, Elmengaard B, Soballe
K: Local bisphosphonate treatment increases
fixation of hydroxyapatite-coated implants inserted
with bone compaction. J Orthop Res, 2008
Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR,
Felsenberg D, et al.: Oral bisphosphonate-induced
osteonecrosis: risk factors, prediction of risk using serum
CTX testing, prevention, and treatment. J Oral
Maxillofac Surg 66:1320-1321; author reply 1321-
1322, 2008
Kyrgidis A, Andreadis C: Clinical characterization might
help in preventing osteonecrosis of the jaw. Clin
Cancer Res 14:8321, 2008
Kyrgidis A, Barbas A: Osteonecrosis of the jaw among
bisphosphonate users. Am J Med 121:e21, 2008
Kyrgidis A, Triaridis S: Regular dental check-ups could be
of benefit for patients receiving intravenous bisphosphonates.
Regarding ‘risks and benefits of bisphosphonates’.
Br J Cancer 0:doi:10.1038/sj.bjc.6604550,
2008
Kyrgidis A, Triaridis S, Vahtsevanos K: New evidence on
bisphosphonate related osteonecrosis of the jaws
suggests dental referral prior to commencement of
treatment. Hippokratia 13:64, 2009
Kyrgidis A, Vahtsevanos K: Increased risk for biphosphonate
related osteonecrosis of the jaws in patients
wearing overdentures could be attributable to
impaired mucosal cell wound healing. J Oral Maxillofac
Surg 0:doi:10.1016/j.joms.2008.1005.1368, 2008
Kyrgidis A, Vahtsevanos K, Koloutsos G, Andreadis C,
Boukovinas I, Teleioudis Z, et al.: Biphosphonate related
osteonecrosis of the jaws: risk factors in breast
cancer patients. A case control study. J Clin Oncol
26:4634-4638 2008
Landesberg R, Cozin M, Cremers S, Woo V, Kousteni S,
Sinha S, et al.: Inhibition of oral mucosal cell wound
healing by bisphosphonates. J Oral Maxillofac Surg
66:839-847, 2008
Magopoulos C, Karakinaris G, Telioudis Z, Vahtsevanos K,
Dimitrakopoulos I, Antoniadis K, et al.: Osteonecrosis
of the jaws due to bisphosphonate use. A review of 60
cases and treatment proposals. AmJOtolaryngol
28:158-163, 2007
Markiewicz MR, Margarone JE, 3rd, Campbell JH, Aguirre
A: Bisphosphonate-associated osteonecrosis of the
jaws: a review of current knowledge. J Am Dent Assoc
136:1669-1674, 2005
Marx RE: Pamidronate (Aredia) and zoledronate
(Zometa) induced avascular necrosis of the jaws: a
growing epidemic. J Oral Maxillofac Surg 61:1115-
1117, 2003
Marx RE, Cillo JE, Jr., Ulloa JJ: Oral bisphosphonate-induced
osteonecrosis: risk factors, prediction of risk using
serum CTX testing, prevention, and treatment. J Oral
Maxillofac Surg 65:2397-2410, 2007
Marx RE, Sawatari Y, Fortin M, Broumand V: Bisphosphonate-
induced exposed bone (osteonecrosis/
osteopetrosis) of the jaws: risk factors, recognition,
prevention, and treatment. J Oral Maxillofac Surg 63:
1567-1575, 2005
Melo MD, Obeid G: Osteonecrosis of the jaws in patients
with a history of receiving bisphosphonate therapy:
strategies for prevention and early recognition. J Am
Dent Assoc 136:1675-1681, 2005
Michaelson MD, Smith MR: Bisphosphonates for treatment
and prevention of bone metastases. JClinOncol
23:8219-8224, 2005
Migliorati CA, Casiglia J, Epstein J, Jacobsen PL, Siegel MA,
Woo SB: Managing the care of patients with bisphosphonate-
associated osteonecrosis: an American
Academy of Oral Medicine position paper. J Am Dent
Assoc 136:1658-1668, 2005
Neville-Webbe HL, Holen I, Coleman RE: The antitumour
activity of bisphosphonates. Cancer TreatRev
28:305-319, 2002
Plotkin H, Rauch F, Bishop NJ, Montpetit K, Ruck-Gibis J,
Travers R, et al.: Pamidronate treatment of severe
osteogenesis imperfecta in children under 3 years of
age. J Clin Endocrinol Metab 85:1846-1850, 2000
Reid IR, Bolland MJ, Grey AB: Is bisphosphonate-associated
osteonecrosis of the jaw caused by soft tissue toxicity?
Bone 41:318-320, 2007
Ruggiero S, Gralow J, Marx RE, Hoff AO, Schubert MM,
Huryn JM, et al.: Practical Guidelines for the Prevention, Diagnosis, and Treatment of Osteonecrosis
of the Jaw in Patients With Cancer. Journal
of Oncology Practice 2:7-14, 2006
Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL:
Osteonecrosis of the jaws associated with the use of
bisphosphonates: a review of 63 cases. J Oral Maxillofac
Surg 62:527-534, 2004
Santini D, Vincenzi B, Galluzzo S, Battistoni F, Rocci L,
Venditti O, et al.: Repeated intermittent low-dose
therapy with zoledronic acid induces an early, sustained,
and long-lasting decrease of peripheral
vascular endothelial growth factor levels in cancer
patients. Clin Cancer Res 13:4482-4486, 2007
Sarin J, DeRossi SS, Akintoye SO: Updates on bisphosphonates
and potential pathobiology of bisphosphonate-
induced jaw osteonecrosis. Oral Dis 14:277-285,
2008
Shane E, Goldring S, Christakos S, Drezner M, Eisman J,
Silverman S, et al.: Osteonecrosis of the jaw: more research
needed. J Bone Miner Res 21:1503-1505, 2006
Stadelmann VA, Gauthier O, Terrier A, Bouler JM, Pioletti
DP: Implants delivering bisphosphonate locally increase
periprosthetic bone density in an osteoporotic
sheep model. A pilot study. Eur Cell Mater 16:10-16,
2008
Starck WJ, Epker BN: Failure of osseointegrated dental
implants after diphosphonate therapy for osteoporosis:
a case report. Int J Oral Maxillofac Implants
10:74-78, 1995
Walter C, Al-Nawas B, Grotz KA, Thomas C, Thuroff JW,
Zinser V, et al.: Prevalence and Risk Factors of Bisphosphonate-
Associated Osteonecrosis of the Jaw in
Prostate Cancer Patients with Advanced Disease
Treated with Zoledronate. Eur Urol 0:doi:10.1016/
j.eururo.2008.1006.1070, 2008
Wermelin K, Suska F, Tengvall P, Thomsen P, Aspenberg
P: Stainless steel screws coated with bisphosphonates
gave stronger fixation and more surrounding bone.
Histomorphometry in rats. Bone 42:365-371, 2008
Whyte MP, Wenkert D, Clements KL, McAlister WH,
Mumm S: Bisphosphonate-induced osteopetrosis. N
Engl J Med 349:457-463, 2003
Woo SB, Hellstein JW, Kalmar JR: Narrative [corrected]
review: bisphosphonates and osteonecrosis of the
jaws. Ann Intern Med 144:753-761, 2006
Wutzl A, Biedermann E, Wanschitz F, Seemann R, Klug C,
Baumann A, et al.: Treatment results of bisphosphonate-
related osteonecrosis of the jaws. Head Neck 30:
1224-1230, 2008
Zervas K, Verrou E, Teleioudis Z, Vahtsevanos K, Banti A,
Mihou D, et al.: Incidence, risk factors and management
of osteonecrosis of the jaw in patients with
multiple myeloma: a single-centre experience in 303
patients. BrJHaematol 134:620-623, 2006
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Σκαπινάκης Π, Stimpson N, Thomas HV, Dusntan V,
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γραφίας στα πλαίσια της Βασισμένης σε Ενδείξεις
Ιατρικής. Αρχ Ελλην Ιατρ 18:192-203, 2001
Κλινική Στοματικής και Γναθοπροσωπικής Χειρουργικής. Οδοντιατρική Σχολή Αριστοτελείου Πανεπιστημίου
Θεσσαλονίκης
(Διευθυντής: Καθηγητής Ν. Λαζαρίδης)
Αρχεία Ελληνικής Στοματικής και Γναθοπροσωπικής Χειρουργικής (2009) 1, 3-14
ΠΕΡΙΛΗΨΗ: Η οστεονέκρωση των γνάθων από διφωσφονικά είναι μια κλινική οντότητα που εμφα-
νίστηκε το 2003 και έκτοτε απασχολεί τον ιατρικό κόσμο. Οι περισσότερες από τις περιπτώσεις ανα-
πτύσσονται σε ασθενείς με πολλαπλό μυέλωμα ή μεταστατικό καρκίνο που λαμβάνουν ενδοφλέβια
αγωγή με διφωσφονικά, αν και έχει περιγραφεί επίσης σε οστεοπορωτικές γυναίκες που αντιμετω-
πίζονται με από του στόματος αγωγή. Στην παρούσα μελέτη γίνεται συστηματική ανασκόπηση της
βιβλιογραφίας για μελέτες που αφορούν την πρόληψη και αντιμετώπιση της νόσου. Προτείνονται
συγκεκριμένα θεραπευτικά πρωτόκολλα αντιμετώπισης της νόσου και περίθαλψης των ασθενών.
Ιδιαίτερη μνεία γίνεται σε νεώτερες διεθνείς μελέτες που αλλάζουν τα μέχρι σήμερα δεδομένα ανα-
φορικά με την πρόληψη και την αντιμετώπιση της νόσου. Ο τακτικός προληπτικός οδοντοστοματο-
λογικός έλεγχος είναι απαραίτητο να εφαρμόζεται πριν και κατά τη διάρκεια της αγωγής με τα σκευ-
άσματα αυτά. Οι ιατροί που χορηγούν διφωσφονικά οφείλουν να ενημερώνουν τον ασθενή τους για
το ενδεχόμενο ανάπτυξης της επιπλοκής και να τον παραπέμπουν στον οδοντίατρο. Χειρουργικές
πράξεις σε ασθενείς που λαμβάνουν διφωσφονικά ενδοφλεβίως σκόπιμο είναι να γίνονται μόνο από
εξοικειωμένους με την επιπλοκή. Στους ασθενείς που νοσούν από οστεονέκρωση η θεραπεία πρέ-
πει να είναι καταρχήν συντηρητική και εφόσον η βλάβη δεν υποχωρεί, οφείλουν να εξεταστούν και
άλλες θεραπευτικές εναλλακτικές λύσεις. Η αντιμετώπιση της επιπλοκής στους ασθενείς αυτούς επι-
βάλλεται να γίνεται από στοματικό και γναθοπροσωπικό χειρουργό.
ΛΕΞΕΙΣ ΚΛΕΙΔΙΑ: Oστεονέκρωση, Oστεομυελίτιδα, Διφωσφονικά, Πρόληψη, Θεραπεία
REFERENCES
Albandar JM: Oral bisphosphonate therapy may not significantly
compromise dental implants success. J Evid Based
Dent Pract 8:229-231, 2008
ASCO (2007) ASCO/NCCN Quality Measures: Breast
and Colorectal Cancers, April 2007 UPDATE.
Bagan JV, Jimenez Y, Diaz JM, Murillo J, Sanchis JM, Poveda
R, et al.: Osteonecrosis of the jaws in intravenous bisphosphonate
use: Proposal for a modification of the
clinical classification. Oral Oncol:In Press, 2008
Bagan JV, Jimenez Y, Murillo J, Hernandez S, Poveda R,
Sanchis JM, et al.: Jaw osteonecrosis associated with
bisphosphonates: multiple exposed areas and its relationship
to teeth extractions. Study of 20 cases. Oral
Oncol 42:327-329, 2006
Bagan JV, Murillo J, Jimenez Y, Poveda R, Milian MA,
Sanchis JM, et al.: Avascular jaw osteonecrosis in association
with cancer chemotherapy: series of 10 cases. J
Oral Pathol Med 34:120-123, 2005
Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos
I, Bozas G, et al.: Osteonecrosis of the jaw in
cancer after treatment with bisphosphonates: incidence
and risk factors. JClinOncol 23:8580-8587, 2005
Bell BM, Bell RE: Oral bisphosphonates and dental implants:
a retrospective study. J Oral Maxillofac Surg 66:
1022-1024, 2008
Body JJ, Coleman RE, Piccart M: Use of bisphosphonates in
cancer patients. Cancer TreatRev 22:265-287, 1996
Brufsky AM: Zoledronic acid for cancer therapy-induced
and postmenopausal bone loss. Expert Opin Pharmacother
9:1013-1028, 2008
Coleman RE: Clinical features of metastatic bone disease
and risk of skeletal morbidity. ClinCancer Res 12:
6243s-6249s, 2006a
Coleman RE: The role of bone markers in metastatic bone
disease. Cancer TreatRev 32 Suppl 1:1-2.:1-2, 2006b
Coleman RE: Risks and benefits of bisphosphonates. Br J
Cancer 98:1736-1740, 2008
Dimopoulos MA, Kastritis E, Anagnostopoulos A, Melakopoulos
I, Gika D, Moulopoulos LA, et al.: Osteonecrosis
of the jaw in patients with multiple myeloma
treated with bisphosphonates: evidence of increased
risk after treatment with zoledronic acid. Haematologica 91:968-971, 2006
Farrugia MC, Summerlin DJ, Krowiak E, Huntley T,
Freeman S, Borrowdale R, et al.: Osteonecrosis of the
mandible or maxilla associated with the use of new generation
bisphosphonates. Laryngoscope 116:115-
120, 2006
Generali D, Dovio A, Tampellini M, Tucci M, Tedoldi S,
Torta M, et al.: Changes of bone turnover markers and
serum PTH after night or morning administration of
zoledronic acid in breast cancer patients with bone
metastases. Br J Cancer 98:1753-1758, 2008
Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G,
Travers R: Cyclic administration of pamidronate in
children with severe osteogenesis imperfecta. N Engl J
Med 339:947-952, 1998
Gomez Font R, Martinez Garcia ML, Olmos Martinez JM:
Osteochemonecrosis of the jaws due to bisphosphonate
treatments. Update. Med Oral Patol Oral Cir
Bucal 13:E318-324, 2008
Hansen T, Kunkel M, Weber A, James Kirkpatrick C: Osteonecrosis
of the jaws in patients treated with bisphosphonates
- histomorphologic analysis in comparison
with infected osteoradionecrosis. J Oral Pathol
Med 35:155-160, 2006
Hashimoto K, Morishige K, Sawada K, Tahara M, Shimizu S,
Ogata S, et al.: Alendronate suppresses tumor angiogenesis
by inhibiting Rho activation of endothelial cells.
Biochem Biophys Res Commun 354:478-484, 2007
Hess LM, Jeter JM, Benham-Hutchins M, Alberts DS:
Factors associated with osteonecrosis of the jaw
among bisphosphonate users. Am J Med 121:475-483
e473, 2008
Jakobsen T, Baas J, Kold S, Bechtold JE, Elmengaard B, Soballe
K: Local bisphosphonate treatment increases
fixation of hydroxyapatite-coated implants inserted
with bone compaction. J Orthop Res, 2008
Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR,
Felsenberg D, et al.: Oral bisphosphonate-induced
osteonecrosis: risk factors, prediction of risk using serum
CTX testing, prevention, and treatment. J Oral
Maxillofac Surg 66:1320-1321; author reply 1321-
1322, 2008
Kyrgidis A, Andreadis C: Clinical characterization might
help in preventing osteonecrosis of the jaw. Clin
Cancer Res 14:8321, 2008
Kyrgidis A, Barbas A: Osteonecrosis of the jaw among
bisphosphonate users. Am J Med 121:e21, 2008
Kyrgidis A, Triaridis S: Regular dental check-ups could be
of benefit for patients receiving intravenous bisphosphonates.
Regarding ‘risks and benefits of bisphosphonates’.
Br J Cancer 0:doi:10.1038/sj.bjc.6604550,
2008
Kyrgidis A, Triaridis S, Vahtsevanos K: New evidence on
bisphosphonate related osteonecrosis of the jaws
suggests dental referral prior to commencement of
treatment. Hippokratia 13:64, 2009
Kyrgidis A, Vahtsevanos K: Increased risk for biphosphonate
related osteonecrosis of the jaws in patients
wearing overdentures could be attributable to
impaired mucosal cell wound healing. J Oral Maxillofac
Surg 0:doi:10.1016/j.joms.2008.1005.1368, 2008
Kyrgidis A, Vahtsevanos K, Koloutsos G, Andreadis C,
Boukovinas I, Teleioudis Z, et al.: Biphosphonate related
osteonecrosis of the jaws: risk factors in breast
cancer patients. A case control study. J Clin Oncol
26:4634-4638 2008
Landesberg R, Cozin M, Cremers S, Woo V, Kousteni S,
Sinha S, et al.: Inhibition of oral mucosal cell wound
healing by bisphosphonates. J Oral Maxillofac Surg
66:839-847, 2008
Magopoulos C, Karakinaris G, Telioudis Z, Vahtsevanos K,
Dimitrakopoulos I, Antoniadis K, et al.: Osteonecrosis
of the jaws due to bisphosphonate use. A review of 60
cases and treatment proposals. AmJOtolaryngol
28:158-163, 2007
Markiewicz MR, Margarone JE, 3rd, Campbell JH, Aguirre
A: Bisphosphonate-associated osteonecrosis of the
jaws: a review of current knowledge. J Am Dent Assoc
136:1669-1674, 2005
Marx RE: Pamidronate (Aredia) and zoledronate
(Zometa) induced avascular necrosis of the jaws: a
growing epidemic. J Oral Maxillofac Surg 61:1115-
1117, 2003
Marx RE, Cillo JE, Jr., Ulloa JJ: Oral bisphosphonate-induced
osteonecrosis: risk factors, prediction of risk using
serum CTX testing, prevention, and treatment. J Oral
Maxillofac Surg 65:2397-2410, 2007
Marx RE, Sawatari Y, Fortin M, Broumand V: Bisphosphonate-
induced exposed bone (osteonecrosis/
osteopetrosis) of the jaws: risk factors, recognition,
prevention, and treatment. J Oral Maxillofac Surg 63:
1567-1575, 2005
Melo MD, Obeid G: Osteonecrosis of the jaws in patients
with a history of receiving bisphosphonate therapy:
strategies for prevention and early recognition. J Am
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