Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates.
BACKGROUND
Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates. The incidence and risk factors associated with this disorder have not been clearly defined.


METHODS
We conducted a retrospective analysis of 4019 patients treated with intravenous bisphosphonates between 1996 and 2004. Our goals were to estimate the frequency, understand the clinical presentation, and identify risk factors associated with ONJ development.


RESULTS
Sixteen of 1338 patients with breast cancer (1.2%) and 13 of 548 patients with multiple myeloma (2.4%) developed ONJ. The median dose and duration of treatment with pamidronate or zoledronic acid were significantly higher in patients with ONJ (p < 0.0001). Multivariate Cox proportional hazards regression analysis identified treatment with zoledronic acid (hazards ratio [HR], 15.01; 95% CI: 2.41-93.48; p = 0.0037), treatment with pamidronate followed by zoledronic acid (HR, 4.00; 95% CI: 0.86-18.70; p = 0.078), and dental extractions (HR, 53.19; 95% CI: 18.20-155.46; p < 0.0001) as significant risks for ONJ in breast cancer. In multiple myeloma, dental extractions (HR, 9.78; 95% CI: 3.07-31.14; p = 0.0001) and osteoporosis (HR, 6.11; 95% CI: 1.56-23.98; p = 0.0095) were significant risk factors while controlling for bisphosphonate therapy. Thirteen of 29 patients were followed for a median of 17.1 mo (range, 7-67 mo); lesions healed in 3 patients during this period.


CONCLUSIONS
ONJ is an uncommon but long-lasting disorder that occurs mainly in breast cancer and multiple myeloma patients treated with intravenous bisphosphonates. High cumulative doses of bisphosphonates, poor oral health, and dental extractions may be significant risk factors for ONJ development. ONJ resolved in 23% of patients with conservative therapy.
Hoff
Ana O
AO
Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. ana.hoff@fleury.com.br
Toth
Béla B
BB
Altundag
Kadri
K
Johnson
Marcella M
MM
Warneke
Carla L
CL
Hu
Mimi
M
Nooka
Ajay
A
Sayegh
Gilbert
G
Guarneri
Valentina
V
Desrouleaux
Kimberly
K
Cui
Jeffrey
J
Adamus
Andrea
A
Gagel
Robert F
RF
Hortobagyi
Gabriel N
GN
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000188:drug therapy / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007573:Jaw Neoplasms / Q000188:drug therapy* / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000453:epidemiology; D010020:Osteonecrosis / Q000139:chemically induced* / Q000453:epidemiology*; D012307:Risk Factors; D013997:Time Factors
D004164:Diphosphonates