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+ = Starck, W.J. and Epker, B.N. : Failure of osseointegrated dental implants after diphosphonate
therapy for osteoporosis : a case report. Int. J.
Oral Maxillofac. Implants, +* : 1.-12, +33/.
, = Wang, E.P., Kaban, L.B., Strewler, G.J., Raje, N.
and Troulis, M.J. : Incidence of osteonecrosis of
the jaw in patients with multiple myeloma and
breast or prostate cancer on intravenous bisphosphonate therapy. J. Oral Maxillofac. Surg. 0+ :
++*.-++*1, ,**-.
- = Marx, R.E. : Pamidronate (Aredia) and Zoledronate (Zometa) induced avascular necrosis of the
jaws : A growing epidemic. J. Oral Maxillofac.
Surg. 0+ : +++/-+++2, ,**-.
. = Migliorati, C.A. : Bisphosphonates and bone
necrosis. J. Clin. Oncol. ,+ : .,/--.,/., ,**-.
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+*= Mehrotra, B. and Ruggiero, S., : Bisphosphonate complications including osteonecrosis of the
jaw. Hematology, ,**0 : -/0--0*, ,**0.
++= Advisory task force on bisphosphonate- related osteonecrosis of the jaws : American association of oral and maxillofacial surgeons position
paper on bisphosphonate-related oasetonecrosis
of the jaws. J. Oral Maxillofac. Surg. 0/ : -03--1/,
,**1.
+,= Ruggiero, S.L., Mehrotra, B., Rosenberg, T.J.
and Engroff, S.L. : Osteonecrosis of the jaws
associated with the use of bisphosphonates : a
review of 0- cases. J. Oral Maxillofac. Surg. 0, :
/,1-/-., ,**..
+-= Gutta, R. and Louis, P.J. : Bisphosphonates and
osteonecrosis of the jaws : Science and rationale.
Oral Surg. Oral Med. Oral Pathol. Oral Radiol.
Endod. +*. : +20-+3-,,**1.
+.= American Dental Association : Osteonecrosis
of the jaw. Available at : http : //www.ada.org/
prof/resources/topics/osteonecrosis.asp
+/= Pucell, P.M. and Boyd, I.W. : Bisphosphonate
and osteonecrosis of the jaw. Med. J. Australia,
+2,: .+1-.+2, ,**/.
+0= Novartis Phamaceuticals Canada Inc. : Updated safety : Possible relationship of Aredia
(pamidronate disodium) and/or Zometa (zoledronic acid) with osteonecrosis of the jaw. Available at : http : //www.hc-sc.gc.ca/dhp-mps/
medeff/advisories-avis/prof/,**./arediaῌzomῌ
hpcῌcpsῌe.html
+1= Hoff, A.O., Toth, B.B., Altundag, K., Guarneri,
V., Adamus, A., Nooka, A.K., Sayegh, G.G., Johnson, M.M., Gagel, R.F. and Hortobagyi, G.N. :
Osteonecrosis of the jaw inpatients receiving
intravenous bisphosphonate therapy. ,**0
ASCO anuual meeting proceedings (postmeeting edition). J. Clinic. Oncology, ,. : 2/,2,
,**0.
+2= Zervas, K., Verrou, E., Teleioudis, Z., Vahtsevanos, K., Banti, K., Mihou, D., Krikelis, D. and
Terpos, E. : Incident, risk factors and management of osteonecrosis of the jaw in patients
with multiple myeloma : a single-centre experience in -*- patients. Br. J. Haematol. +-. : 0,*-0,-,
,**0.
+3= Mavrokokki, T., Cheng, A., Stein, B. and Goss,
A. : Nature and frequency of bisphosphonateassociated osteonecrosis of the jaws in Australia. J. Oral Maxillofac. Surg. 0/ : .+/-.,-, ,**1.
,*= Dunstan, C.R., Felsenberg, D. and Seibel, M.J. :
Therapy insight : the risk and benefits of bisphosphonates for the treatment of tumor-induced
bone disease. Nat. Clin. Pract. Oncol. . : .,-//,
,**1.
,+= Novartis : Updated recommendations for the
prevention, diagnosis, and treatment of osteonecrosis of the jaw in cancer patients : May ,**0.
Available at : http : //www.novartis.co.jp/product/zom/te/teῌarezom*0*1ῌa.html
,,= Freiberger, J.J., Padilla-Burgos, R., Chhoeeu, A.
H., Kraft, K.H., Boneta, O., Moon, R.E. and Piantadosi, C.A. : Hyperbaric oxygen treatment and
bisphosphonate-induced osteonecrosis of the
jaw : a case siries. J. Oral Maxillofac. Sung. 0/ :
+-,+-+-,1, ,**1.
,-= Harper, R.P. and Fung, E.F. : Resolution of
bisphosphonate-associated osteonecrosis of the
mandible : Possible application for intermittent
low-dose parathyroid hormone [rhPTM ( + --.)].
J. Oral Maxillofac. Surg. 0/ : /1--/2*, ,**1.