Time to onset of bisphosphonate-related osteonecrosis of the jaws

a multicentre retrospective cohort study

GENVABO Consortium

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Objectives: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients. Subjects and Methods: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012. Results: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate. Conclusions: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.

Original languageEnglish
Pages (from-to)477-483
Number of pages7
JournalOral Diseases
Volume23
Issue number4
DOIs
Publication statusPublished - May 1 2017

Fingerprint

Bisphosphonate-Associated Osteonecrosis of the Jaw
Diphosphonates
Osteonecrosis
zoledronic acid
Jaw
Cohort Studies
Retrospective Studies
Alendronate
Secondary Care Centers
Risk Reduction Behavior
Therapeutics
Osteoporosis
Neoplasms
Incidence

Keywords

  • bisphosphonates
  • breast cancer
  • jaw osteonecrosis
  • multiple myeloma
  • osteoporosis
  • prostate cancer

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Dentistry(all)

Cite this

Time to onset of bisphosphonate-related osteonecrosis of the jaws : a multicentre retrospective cohort study. / GENVABO Consortium.

In: Oral Diseases, Vol. 23, No. 4, 01.05.2017, p. 477-483.

Research output: Contribution to journalArticle

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title = "Time to onset of bisphosphonate-related osteonecrosis of the jaws: a multicentre retrospective cohort study",
abstract = "Objectives: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients. Subjects and Methods: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012. Results: The median (95{\%}CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate. Conclusions: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50{\%} of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50{\%} of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.",
keywords = "bisphosphonates, breast cancer, jaw osteonecrosis, multiple myeloma, osteoporosis, prostate cancer",
author = "{GENVABO Consortium} and Fung, {P. P.L.} and G. Bedogni and A. Bedogni and A. Petrie and S. Porter and G. Campisi and J. Bagan and V. Fusco and G. Saia and S. Acham and P. Musto and Petrucci, {M. T.} and P. Diz and G. Colella and Mignogna, {M. D.} and M. Pentenero and P. Arduino and G. Lodi and C. Maiorana and M. Manfredi and P. Hallberg and M. Wadelius and K. Takaoka and Leung, {Y. Y.} and R. Bonacina and M. Schi{\o}dt and P. Lakatos and T. Taylor and {De Riu}, G. and G. Favini and Rogers, {S. N.} and M. Pirmohamed and P. Nicoletti and S. Fedele and L{\'o}pez-Cedr{\'u}n, {Jose L.} and Sanne Madsen and Gennaro Sadile and Stefania Leuci and Cristina Mirelli and Giulio Conti and Rita Maiavacca and Masahiro Urade and Hiromitsu Kishimoto and Shin Okui and Yusuke Zushi and Michiyo Yamamura and Kyohei Yoshikawa and Giovanna Mansueto and Magnusson, {Patrik K.E.} and Shina Popat",
year = "2017",
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TY - JOUR

T1 - Time to onset of bisphosphonate-related osteonecrosis of the jaws

T2 - a multicentre retrospective cohort study

AU - GENVABO Consortium

AU - Fung, P. P.L.

AU - Bedogni, G.

AU - Bedogni, A.

AU - Petrie, A.

AU - Porter, S.

AU - Campisi, G.

AU - Bagan, J.

AU - Fusco, V.

AU - Saia, G.

AU - Acham, S.

AU - Musto, P.

AU - Petrucci, M. T.

AU - Diz, P.

AU - Colella, G.

AU - Mignogna, M. D.

AU - Pentenero, M.

AU - Arduino, P.

AU - Lodi, G.

AU - Maiorana, C.

AU - Manfredi, M.

AU - Hallberg, P.

AU - Wadelius, M.

AU - Takaoka, K.

AU - Leung, Y. Y.

AU - Bonacina, R.

AU - Schiødt, M.

AU - Lakatos, P.

AU - Taylor, T.

AU - De Riu, G.

AU - Favini, G.

AU - Rogers, S. N.

AU - Pirmohamed, M.

AU - Nicoletti, P.

AU - Fedele, S.

AU - López-Cedrún, Jose L.

AU - Madsen, Sanne

AU - Sadile, Gennaro

AU - Leuci, Stefania

AU - Mirelli, Cristina

AU - Conti, Giulio

AU - Maiavacca, Rita

AU - Urade, Masahiro

AU - Kishimoto, Hiromitsu

AU - Okui, Shin

AU - Zushi, Yusuke

AU - Yamamura, Michiyo

AU - Yoshikawa, Kyohei

AU - Mansueto, Giovanna

AU - Magnusson, Patrik K.E.

AU - Popat, Shina

PY - 2017/5/1

Y1 - 2017/5/1

N2 - Objectives: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients. Subjects and Methods: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012. Results: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate. Conclusions: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.

AB - Objectives: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients. Subjects and Methods: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012. Results: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate. Conclusions: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.

KW - bisphosphonates

KW - breast cancer

KW - jaw osteonecrosis

KW - multiple myeloma

KW - osteoporosis

KW - prostate cancer

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U2 - 10.1111/odi.12632

DO - 10.1111/odi.12632

M3 - Article

VL - 23

SP - 477

EP - 483

JO - Oral Diseases

JF - Oral Diseases

SN - 1354-523X

IS - 4

ER -