Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors.
OBJECTIVE
Osteonecrosis of the jaw (ONJ) has been associated recently with the use of pamidronate and zoledronic acid. We studied the incidence, characteristics, and risk factors for the development of ONJ among patients treated with bisphosphonates for bone metastases.


METHODS
ONJ was assessed prospectively since July 2003. The first bisphosphonate treatment among patients with ONJ was administered in 1997. Two hundred fifty-two patients who received bisphosphonates since January 1997 were included in this analysis.


RESULTS
Seventeen patients (6.7%) developed ONJ: 11 of 111 (9.9%) with multiple myeloma, two of 70 (2.9%) with breast cancer, three of 46 (6.5%) with prostate cancer, and one of 25 (4%) with other neoplasms (P = .289). The median number of treatment cycles and time of exposure to bisphosphonates were 35 infusions and 39.3 months for patients with ONJ compared with 15 infusions (P < .001) and 19 months (P = .001), respectively, for patients with no ONJ. The incidence of ONJ increased with time to exposure from 1.5% among patients treated for 4 to 12 months to 7.7% for treatment of 37 to 48 months. The cumulative hazard was significantly higher with zoledronic acid compared with pamidronate alone or pamidronate and zoledronic acid sequentially (P < .001). All but two patients with ONJ had a history of dental procedures within the last year or use of dentures.


CONCLUSIONS
The use of bisphosphonates seems to be associated with the development of ONJ. Length of exposure seems to be the most important risk factor for this complication. The type of bisphosphonate may play a role and previous dental procedures may be a precipitating factor.
Bamias
Aristotle
A
Department of Clinical Therapeutics, Medical School, University of Athens, Greece.
Kastritis
Efstathios
E
Bamia
Christina
C
Moulopoulos
Lia A
LA
Melakopoulos
Ioannis
I
Bozas
George
G
Koutsoukou
Vassiliki
V
Gika
Dimitra
D
Anagnostopoulos
Athanasios
A
Papadimitriou
Christos
C
Terpos
Evagelos
E
Dimopoulos
Meletios A
MA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D004164:Diphosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006115:Greece / Q000453:epidemiology; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D007571:Jaw Diseases / Q000139:chemically induced* / Q000188:drug therapy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000473:pathology; D010020:Osteonecrosis / Q000139:chemically induced* / Q000188:drug therapy / Q000453:epidemiology; D000077268:Pamidronate; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D012307:Risk Factors; D013997:Time Factors; D017211:Treatment Failure; D000077211:Zoledronic Acid
D000900:Anti-Bacterial Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000077268:Pamidronate