SAA Shah, A Aslam, AI Mirza, S Ali


Bisphosphonates are used widely for a variety of bone conditions, most notably intravenous
bisphosphonate in the treatment of metastatic bone lesions and multiple myeloma and oral
bisphosphonates for osteoporosis. Recently, a peculiar form of osteonecrosis limited to the jaws has
been discovered especially with the use of intravenous bisphosphonates. We review briefly the
mechanism of action of these drugs, the clinical features and staging of the disease, prevention
strategies and management options.
Keyword: BRONJ, Multiple myeloma, Hyperbaric oxygen

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Sato M, Grasser W, Endo N, Akins R, Simmons H,

Thompson DD, et al. Bisphosphonates action. Alendronate

localization in rat bone and effects on osteoclast

ultrastructure. J Clin Invest 1991;88:2095‒105.

Russell RG, Bisaz S, Fleisch H, Currey HL, Rubinstein HM,

Dietz AA, et al. Inorganic pyrophosphate in plasma, urine,

and synovial fluid of patients with pyrophosphate

arthropathy (chondrocalcinosis or pseudogut). Lancet


Rodan GA, Reszka AA. Bisphosphonate mechanism of

action. Curr Mol Med 2002;2:571‒7.

Rogers MJ, Gordon S, Benford HL, et al. Cellular and

molecular mechanisms of action of bisphosphonates. Cancer


American College of Obstetricians and Gynecologists,

Women’s Health Care Physicians. ACOG practice bulletin.

Clinical management guidelines for obstetriciansgynecologists. Obstet Gynecol 2004;103:203‒16.

Hortobagyi GN, Theriualt RL, Porter I, et al. Efficacy of

pamidronate in reducing skeletal complications in patients

with breast cancer and lytic bone metastasis. N Engl J Med


Berenson JR, Lichtenstein A, Porter L, Dimopoulos MA,

Bordoni R, George S, et al. Efficacy of pamidronate in

reducing skeletal events in patients with advanced multiple

myeloma. N Engl J Med 1996;334:448‒93.

Berenson JR, Hillner BE, Kyle RA, Anderson K, Lipton A,

Yee GC, et al. American society of clinical oncology clinical

practice guidelines: the role of bisphosphonates in multiple

myeloma. J Clin Oncol 2002;20:3719‒36.

Conte P, Guarneri V. Safety of intravenous and oral

bisphosphonates and compliance with dosing regimens.

Oncologist 2004;9:28‒37.

Marx RE. Pamidronate (Aredia) and zoledronate (Zometa)

induced avascular necrosis of the jaws: a growing epidemic.

J Oral Maxillofac Surg 2003;61:1115‒7.

Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff S.

Osteonecrosis of the jaws associated with the use of

bisphosphonates: a review of 63 cases. J Oral Maxillofac

Surg 2004;62:527‒34.

Robinson NA, Yeo JF. Bisphosphonates: a word of caution.

Ann Acad Med Singapore 2004;33:48–9.

Migliorati CA, Schubert MM, Peterson DE, Seneda LM.

Bisphosphonates-associated osteonecrosis of mandibular and

maxillary bone: an emerging oral complication of supportive

cancer therapy. Cancer 2005;104:83‒93.

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


Advisory Task Force on Bisphosphonate-Related

Ostenonecrosis of the Jaws, American Association of Oral

and Maxillofacial Surgeons. American association of oral

and maxillofacial surgeons position paper on

bisphosphonate-related osteonecrosis of the jaws. J Oral

Maxillofac Surg 2007;65:369‒76.

Marx RE. Osteoradionecrosis: A new concept of its

pathophysiology. J Oral Maxillofac Surg 1983;41:351.

Marx RE, Johnson RP. Studies in the radiobiology of

osteoradionecrosis and their clinical significance. Oral Surg

Oral Med Oral Pathol 1987;64:379.

Marx RE, Cillo JE, Ulloa JJ. Oral Bisphosphonate-Induced

Osteonecrosis: Risk Factors, Prediction of Risk Using Serum

CTX Testing, Prevention, and Treatment. J Oral Maxillofac

Surg 2007;65:2397‒410.

Ruggiero SL, Fantasia J, Carlson E. Bisphosphonate-related

osteonecrosis of the jaw: Background and guidelines for

diagnosis, staging and management. Oral Surg Oral Med

Oral Pathol Oral Radiol Endod 2006;102:433‒41.

Freiberger JJ, Padilla-Burgos R, Chhoeu AH, Kraft KH,

Boneta O, Moon RE, et al. Hyperbaric Oxygen Treatment

and Bisphosphonate-Induced Osteonecrosis of the Jaw: A

Case Series. J Oral Maxillofac Surg 2007;65:1321‒7.

Curi MM, Cossolin GS, Koga DH, Araújo SR, Feher O, dos

Santos MO, et al. Treatment of avascular osteonecrosis of

the mandible in cancer patients with a history of

bisphosphonate therapy by combining bone resection and

autologous platelet-rich plasma: Report of 3 cases. J Oral

Maxillofac Surg 2007;65:349‒55.

Engroff SL, Kim DD. Treating bisphosphonate osteonecrosis

of the jaws: Is there a role for resection and vascularized

reconstruction? J Oral Maxillofac Surg 2007;65:2374‒85.

Harper RP, Fung E. Resolution of bisphosphonate-associated

osteonecrosis of the mandible: possible application for

intermittent low-dose parathyroid hormone [rhPTH(1-34)]. J

Oral Maxillofac Surg 2007;65:573‒80.


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