Time to onset of bisphosphonate-related osteonecrosis of the jaws

a multicentre retrospective cohort study

Ppl Fung, G. Bedogni, A. Bedogni, A. Petrie, Stephen Ross Porter, G. Campisi, J Bagan, V Fusco, G. Saia, S Acham, P Musto, Maria T. Petrucci, P Diz, G Colella, M. D. Mignogna, Monica Pentenero, P. Arduino, G. Lodi, C Maiorana, M. Manfredi & 15 others P Hallberg, M. Wadelius, K Takaoka, S. Y. Leung, R. Bonacina, M Schiødt, P. L. Lakatos, T. Taylor, Giacomo De Riu, G. Favini, S N Rogers, Munir Pirmohamed, P. Nicoletti, S. Fedele, GENVABO Consortium

Research output: Contribution to journalArticle

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
JournalOral Diseases
DOIs
Publication statusE-pub ahead of print - Dec 31 2016

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

  • Journal Article

Cite this

Fung, P., Bedogni, G., Bedogni, A., Petrie, A., Porter, S. R., Campisi, G., ... GENVABO Consortium (2016). Time to onset of bisphosphonate-related osteonecrosis of the jaws: a multicentre retrospective cohort study. Oral Diseases. https://doi.org/10.1111/odi.12632

Time to onset of bisphosphonate-related osteonecrosis of the jaws : a multicentre retrospective cohort study. / Fung, Ppl; Bedogni, G.; Bedogni, A.; Petrie, A.; Porter, Stephen Ross; Campisi, G.; Bagan, J; Fusco, V; Saia, G.; Acham, S; Musto, P; Petrucci, Maria T.; Diz, P; Colella, G; Mignogna, M. D.; Pentenero, Monica; Arduino, P.; Lodi, G.; Maiorana, C; Manfredi, M.; Hallberg, P; Wadelius, M.; Takaoka, K; Leung, S. Y.; Bonacina, R.; Schiødt, M; Lakatos, P. L.; Taylor, T.; De Riu, Giacomo; Favini, G.; Rogers, S N; Pirmohamed, Munir; Nicoletti, P.; Fedele, S.; GENVABO Consortium.

In: Oral Diseases, 31.12.2016.

Research output: Contribution to journalArticle

Fung, P, Bedogni, G, Bedogni, A, Petrie, A, Porter, SR, Campisi, G, Bagan, J, Fusco, V, Saia, G, Acham, S, Musto, P, Petrucci, MT, Diz, P, Colella, G, Mignogna, MD, Pentenero, M, Arduino, P, Lodi, G, Maiorana, C, Manfredi, M, Hallberg, P, Wadelius, M, Takaoka, K, Leung, SY, Bonacina, R, Schiødt, M, Lakatos, PL, Taylor, T, De Riu, G, Favini, G, Rogers, SN, Pirmohamed, M, Nicoletti, P, Fedele, S & GENVABO Consortium 2016, 'Time to onset of bisphosphonate-related osteonecrosis of the jaws: a multicentre retrospective cohort study', Oral Diseases. https://doi.org/10.1111/odi.12632
Fung, Ppl ; Bedogni, G. ; Bedogni, A. ; Petrie, A. ; Porter, Stephen Ross ; Campisi, G. ; Bagan, J ; Fusco, V ; Saia, G. ; Acham, S ; Musto, P ; Petrucci, Maria T. ; Diz, P ; Colella, G ; Mignogna, M. D. ; Pentenero, Monica ; Arduino, P. ; Lodi, G. ; Maiorana, C ; Manfredi, M. ; Hallberg, P ; Wadelius, M. ; Takaoka, K ; Leung, S. Y. ; Bonacina, R. ; Schiødt, M ; Lakatos, P. L. ; Taylor, T. ; De Riu, Giacomo ; Favini, G. ; Rogers, S N ; Pirmohamed, Munir ; Nicoletti, P. ; Fedele, S. ; GENVABO Consortium. / Time to onset of bisphosphonate-related osteonecrosis of the jaws : a multicentre retrospective cohort study. In: Oral Diseases. 2016.
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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.",
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TY - JOUR

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

T2 - a multicentre retrospective cohort study

AU - Fung, Ppl

AU - Bedogni, G.

AU - Bedogni, A.

AU - Petrie, A.

AU - Porter, Stephen Ross

AU - Campisi, G.

AU - Bagan, J

AU - Fusco, V

AU - Saia, G.

AU - Acham, S

AU - Musto, P

AU - Petrucci, Maria T.

AU - Diz, P

AU - Colella, G

AU - Mignogna, M. D.

AU - Pentenero, Monica

AU - Arduino, P.

AU - Lodi, G.

AU - Maiorana, C

AU - Manfredi, M.

AU - Hallberg, P

AU - Wadelius, M.

AU - Takaoka, K

AU - Leung, S. Y.

AU - Bonacina, R.

AU - Schiødt, M

AU - Lakatos, P. L.

AU - Taylor, T.

AU - De Riu, Giacomo

AU - Favini, G.

AU - Rogers, S N

AU - Pirmohamed, Munir

AU - Nicoletti, P.

AU - Fedele, S.

AU - GENVABO Consortium

N1 - © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2016/12/31

Y1 - 2016/12/31

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 - Journal Article

U2 - 10.1111/odi.12632

DO - 10.1111/odi.12632

M3 - Article

JO - Oral Diseases

JF - Oral Diseases

SN - 1354-523X

ER -