Longitudinal cohort study of risk factors in cancer patients of bisphosphonate-related osteonecrosis of the jaw.
OBJECTIVE
The reported incidence of osteonecrosis of the jaw (ONJ) ranges from 0.94% to 18.6%. This cohort study aimed to calculate the incidence of and identify the risk factors for ONJ in patients with cancer treated with intravenous zoledronate, ibandronate, and pamidronate.


METHODS
Data analyzed included age, sex, smoking status, underlying disease, medical and dental history, bisphosphonates (BP) type, and doses administered. Relative risks, crude and adjusted odds ratios (aORs), and cumulative hazard ratios for ONJ development were calculated.


RESULTS
We included 1,621 patients who received 29,006 intravenous doses of BP, given monthly. Crude ONJ incidence was 8.5%, 3.1%, and 4.9% in patients with multiple myeloma, breast cancer, and prostate cancer, respectively. Patients with breast cancer demonstrated a reduced risk for ONJ development, which turned out to be nonsignificant after adjustment for other variables. Multivariate analysis demonstrated that use of dentures (aOR = 2.02; 95% CI, 1.03 to 3.96), history of dental extraction (aOR = 32.97; 95% CI, 18.02 to 60.31), having ever received zoledronate (aOR = 28.09; 95% CI, 5.74 to 137.43), and each zoledronate dose (aOR = 2.02; 95% CI, 1.15 to 3.56) were associated with increased risk for ONJ development. Smoking, periodontitis, and root canal treatment did not increase risk for ONJ in patients receiving BP.


CONCLUSIONS
The conclusions of this study validated dental extractions and use of dentures as risk factors for ONJ development. Ibandronate and pamidronate at the dosages and frequency used in this study seem to exhibit a safer drug profile concerning ONJ complication; however, randomized controlled trials are needed to validate these results. Before initiation of a bisphosphonate, patients should have a comprehensive dental examination. Patients with a challenging dental situation should have dental care attended to before initiation of these drugs.
Vahtsevanos
Konstantinos
K
Departments of Oral Maxillofacial Surgery, Theagenio Cancer Hospital, Thessaloniki, Greece.
Kyrgidis
Athanassios
A
Verrou
Evgenia
E
Katodritou
Eirini
E
Triaridis
Stefanos
S
Andreadis
Charalampos G
CG
Boukovinas
Ioannis
I
Koloutsos
Georgios E
GE
Teleioudis
Zisis
Z
Kitikidou
Kyriaki
K
Paraskevopoulos
Panagiotis
P
Zervas
Konstantinos
K
Antoniades
Konstantinos
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006115:Greece / Q000453:epidemiology; D006801:Humans; D000077557:Ibandronic Acid; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects; D015994:Incidence; D007571:Jaw Diseases / Q000139:chemically induced* / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy; D010020:Osteonecrosis / Q000139:chemically induced* / Q000453:epidemiology; D000077268:Pamidronate; D011471:Prostatic Neoplasms / Q000188:drug therapy; D012307:Risk Factors; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000077268:Pamidronate; D000077557:Ibandronic Acid