Intravenous bisphosphonate therapy and inflammatory conditions or surgery of the jaw

A population-based analysis

Gregg S. Wilkinson, Yong Fang Kuo, Jean L. Freeman, James Goodwin

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Background: Recent reports have identified an association between osteonecrosis of the jaw or facial bones and treatment with nitrogen-containing intravenous bisphosphonates. We investigated this association by use of data from the Surveillance, Epidemiology, and End. Results (SEER) program linked to Medicare claims. Methods: We identified 16073 cancer patients who were diagnosed between January 1, 1986, and December 31, 2002, and were treated intravenously with the bisphosphonates pamidronate and/or zoledronic acid between January 1, 1995, and December 31, 2003. We matched 28698 bisphosphonate nonusers, at a 2:1 ratio, to 14349 bisphosphonate users on month and year of the first bisphosphonate administration received by users, cancer type, age, sex, risk factors for osteonecrosis (diabetes, alcoholism, cigarette smoking, obesity, hyperlipemia, pancreatitis, or chemotherapy with L-asparaginase), bone metastasis, and SEER program geographic region. Patients were followed until the study's end on December 31, 2003; loss of coverage from Medicare Parts A and B; or one of the following outcomes: a diagnosis of inflammatory conditions or osteomyelitis of the jaw, surgery on the facial bones, or death, whichever occurred first. Results: Use of intravenous bisphosphonates was associated with an increased risk of jaw or facial bone surgery (hazard ratio [HR] = 3.15, 95% confidence interval [CI] = 1.86 to 5.32) and an increased risk of being diagnosed with inflammatory conditions or osteomyelitis of the jaw (HR = 11.48, 95% CI = 6.49 to 20.33), compared with nonuse. The absolute risk at 6 years for any jaw toxicity was 5.48 events per 100 patients using intravenous bisphosphonates and 0.30 events per 100 patients not using such drugs. The risk of each outcome increased as cumulative dose increased (e.g., for 4-8 infusions, HR for operations on the jaw and facial bones = 3.63, 95% CI = 0.77 to 17.08; for more than 21 infusions, HR = 9.18, 95% CI = 1.74 to 48.53). Conclusion: Users of intravenous bisphosphonates had an increased risk of inflammatory conditions, osteomyelitis, and surgical procedures of the jaw and facial bones. The increased risk may reflect an increased risk for osteonecrosis of the jaw.

Original languageEnglish (US)
Pages (from-to)1016-1024
Number of pages9
JournalJournal of the National Cancer Institute
Volume99
Issue number13
DOIs
StatePublished - Jul 4 2007

Fingerprint

Orthognathic Surgery
Diphosphonates
Jaw
Facial Bones
Population
Osteonecrosis
Osteomyelitis
Confidence Intervals
pamidronate
zoledronic acid
Therapeutics
Medicare Part A
Epidemiology
Medicare Part B
Sex Factors
Asparaginase
Medicare
Hyperlipidemias
Pancreatitis
Alcoholism

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Intravenous bisphosphonate therapy and inflammatory conditions or surgery of the jaw : A population-based analysis. / Wilkinson, Gregg S.; Kuo, Yong Fang; Freeman, Jean L.; Goodwin, James.

In: Journal of the National Cancer Institute, Vol. 99, No. 13, 04.07.2007, p. 1016-1024.

Research output: Contribution to journalArticle

@article{38d73cb749904f3abed8f9167f52259b,
title = "Intravenous bisphosphonate therapy and inflammatory conditions or surgery of the jaw: A population-based analysis",
abstract = "Background: Recent reports have identified an association between osteonecrosis of the jaw or facial bones and treatment with nitrogen-containing intravenous bisphosphonates. We investigated this association by use of data from the Surveillance, Epidemiology, and End. Results (SEER) program linked to Medicare claims. Methods: We identified 16073 cancer patients who were diagnosed between January 1, 1986, and December 31, 2002, and were treated intravenously with the bisphosphonates pamidronate and/or zoledronic acid between January 1, 1995, and December 31, 2003. We matched 28698 bisphosphonate nonusers, at a 2:1 ratio, to 14349 bisphosphonate users on month and year of the first bisphosphonate administration received by users, cancer type, age, sex, risk factors for osteonecrosis (diabetes, alcoholism, cigarette smoking, obesity, hyperlipemia, pancreatitis, or chemotherapy with L-asparaginase), bone metastasis, and SEER program geographic region. Patients were followed until the study's end on December 31, 2003; loss of coverage from Medicare Parts A and B; or one of the following outcomes: a diagnosis of inflammatory conditions or osteomyelitis of the jaw, surgery on the facial bones, or death, whichever occurred first. Results: Use of intravenous bisphosphonates was associated with an increased risk of jaw or facial bone surgery (hazard ratio [HR] = 3.15, 95{\%} confidence interval [CI] = 1.86 to 5.32) and an increased risk of being diagnosed with inflammatory conditions or osteomyelitis of the jaw (HR = 11.48, 95{\%} CI = 6.49 to 20.33), compared with nonuse. The absolute risk at 6 years for any jaw toxicity was 5.48 events per 100 patients using intravenous bisphosphonates and 0.30 events per 100 patients not using such drugs. The risk of each outcome increased as cumulative dose increased (e.g., for 4-8 infusions, HR for operations on the jaw and facial bones = 3.63, 95{\%} CI = 0.77 to 17.08; for more than 21 infusions, HR = 9.18, 95{\%} CI = 1.74 to 48.53). Conclusion: Users of intravenous bisphosphonates had an increased risk of inflammatory conditions, osteomyelitis, and surgical procedures of the jaw and facial bones. The increased risk may reflect an increased risk for osteonecrosis of the jaw.",
author = "Wilkinson, {Gregg S.} and Kuo, {Yong Fang} and Freeman, {Jean L.} and James Goodwin",
year = "2007",
month = "7",
day = "4",
doi = "10.1093/jnci/djm025",
language = "English (US)",
volume = "99",
pages = "1016--1024",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "13",

}

TY - JOUR

T1 - Intravenous bisphosphonate therapy and inflammatory conditions or surgery of the jaw

T2 - A population-based analysis

AU - Wilkinson, Gregg S.

AU - Kuo, Yong Fang

AU - Freeman, Jean L.

AU - Goodwin, James

PY - 2007/7/4

Y1 - 2007/7/4

N2 - Background: Recent reports have identified an association between osteonecrosis of the jaw or facial bones and treatment with nitrogen-containing intravenous bisphosphonates. We investigated this association by use of data from the Surveillance, Epidemiology, and End. Results (SEER) program linked to Medicare claims. Methods: We identified 16073 cancer patients who were diagnosed between January 1, 1986, and December 31, 2002, and were treated intravenously with the bisphosphonates pamidronate and/or zoledronic acid between January 1, 1995, and December 31, 2003. We matched 28698 bisphosphonate nonusers, at a 2:1 ratio, to 14349 bisphosphonate users on month and year of the first bisphosphonate administration received by users, cancer type, age, sex, risk factors for osteonecrosis (diabetes, alcoholism, cigarette smoking, obesity, hyperlipemia, pancreatitis, or chemotherapy with L-asparaginase), bone metastasis, and SEER program geographic region. Patients were followed until the study's end on December 31, 2003; loss of coverage from Medicare Parts A and B; or one of the following outcomes: a diagnosis of inflammatory conditions or osteomyelitis of the jaw, surgery on the facial bones, or death, whichever occurred first. Results: Use of intravenous bisphosphonates was associated with an increased risk of jaw or facial bone surgery (hazard ratio [HR] = 3.15, 95% confidence interval [CI] = 1.86 to 5.32) and an increased risk of being diagnosed with inflammatory conditions or osteomyelitis of the jaw (HR = 11.48, 95% CI = 6.49 to 20.33), compared with nonuse. The absolute risk at 6 years for any jaw toxicity was 5.48 events per 100 patients using intravenous bisphosphonates and 0.30 events per 100 patients not using such drugs. The risk of each outcome increased as cumulative dose increased (e.g., for 4-8 infusions, HR for operations on the jaw and facial bones = 3.63, 95% CI = 0.77 to 17.08; for more than 21 infusions, HR = 9.18, 95% CI = 1.74 to 48.53). Conclusion: Users of intravenous bisphosphonates had an increased risk of inflammatory conditions, osteomyelitis, and surgical procedures of the jaw and facial bones. The increased risk may reflect an increased risk for osteonecrosis of the jaw.

AB - Background: Recent reports have identified an association between osteonecrosis of the jaw or facial bones and treatment with nitrogen-containing intravenous bisphosphonates. We investigated this association by use of data from the Surveillance, Epidemiology, and End. Results (SEER) program linked to Medicare claims. Methods: We identified 16073 cancer patients who were diagnosed between January 1, 1986, and December 31, 2002, and were treated intravenously with the bisphosphonates pamidronate and/or zoledronic acid between January 1, 1995, and December 31, 2003. We matched 28698 bisphosphonate nonusers, at a 2:1 ratio, to 14349 bisphosphonate users on month and year of the first bisphosphonate administration received by users, cancer type, age, sex, risk factors for osteonecrosis (diabetes, alcoholism, cigarette smoking, obesity, hyperlipemia, pancreatitis, or chemotherapy with L-asparaginase), bone metastasis, and SEER program geographic region. Patients were followed until the study's end on December 31, 2003; loss of coverage from Medicare Parts A and B; or one of the following outcomes: a diagnosis of inflammatory conditions or osteomyelitis of the jaw, surgery on the facial bones, or death, whichever occurred first. Results: Use of intravenous bisphosphonates was associated with an increased risk of jaw or facial bone surgery (hazard ratio [HR] = 3.15, 95% confidence interval [CI] = 1.86 to 5.32) and an increased risk of being diagnosed with inflammatory conditions or osteomyelitis of the jaw (HR = 11.48, 95% CI = 6.49 to 20.33), compared with nonuse. The absolute risk at 6 years for any jaw toxicity was 5.48 events per 100 patients using intravenous bisphosphonates and 0.30 events per 100 patients not using such drugs. The risk of each outcome increased as cumulative dose increased (e.g., for 4-8 infusions, HR for operations on the jaw and facial bones = 3.63, 95% CI = 0.77 to 17.08; for more than 21 infusions, HR = 9.18, 95% CI = 1.74 to 48.53). Conclusion: Users of intravenous bisphosphonates had an increased risk of inflammatory conditions, osteomyelitis, and surgical procedures of the jaw and facial bones. The increased risk may reflect an increased risk for osteonecrosis of the jaw.

UR - http://www.scopus.com/inward/record.url?scp=34447252128&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34447252128&partnerID=8YFLogxK

U2 - 10.1093/jnci/djm025

DO - 10.1093/jnci/djm025

M3 - Article

VL - 99

SP - 1016

EP - 1024

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 13

ER -