Time to onset of bisphosphonate‐related osteonecrosis of the jaws: a multicentre retrospective cohort study. (6th March 2017)

• Record Type: Journal Article
• Authors: Fung, PPL; Bedogni, G; Bedogni, A; Petrie, A; Porter, S; 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, YY; Bonacina, R; Schiødt, M; Lakatos, P; Taylor, T; De Riu, G; Favini, G; Rogers, SN; Pirmohamed, M; Nicoletti, P; Fedele, S;
• Other Names: López‐Cedrún Jose L investigator.; Madsen Sanne investigator.; Sadile Gennaro investigator.; Leuci Stefania investigator.; Mirelli Cristina investigator.; Conti Giulio investigator.; Maiavacca Rita investigator.; Urade Masahiro investigator.; Kishimoto Hiromitsu investigator.; Okui Shin investigator.; Zushi Yusuke investigator.; Yamamura Michiyo investigator.; Yoshikawa Kyohei investigator.; Mansueto Giovanna investigator.; Magnusson Patrik KE investigator.; Popat Shina investigator.; Kirnbauer Barbara investigator.; Obermayer‐Pietsch Barbara investigator.; Jakse Norbert investigator.; Mariani Umberto investigator.; Martini Valeria investigator.; Fasciolo Antonella investigator.; De Martino Iolanda investigator.; Alessio Manuela investigator.; Sanromán Jacinto F investigator.; Grammatico Sara investigator.; Siniscalchi Giovanni investigator.; Itro Angelo investigator.; Balla Bernadett investigator.; Kosa Janos P investigator.; Vaszilko Mihaly investigator.; Lo John investigator.; Besi Eleni investigator.; D'Aiuto Francesco investigator.; Yong Kwee investigator.; Donos Nikos investigator.; Mercadante Valeria investigator.; Stein Robert investigator.; D'Sa Shirley investigator.; Varoni Elena investigator.; Soma Damiano investigator.; Meloni Silvio investigator.; Evely Jane investigator.; Hanson Anita investigator.; Giancola Francesco investigator.; Di Fede Olga investigator.; Panzarella Vera investigator.; Bettini Giordana investigator.; Merigo Elisabetta investigator.; Mergoni Giovanni investigator.; Vescovi Paolo investigator.; Gandolfo Sergio investigator.; Marino Roberto investigator.; Berrone Mattia investigator.; Gambino Alessio investigator.; Menegatti Elisa investigator.; Broccoletti Roberto investigator.; Hens Elena investigator.; Bagan Leticia investigator.;
• Is Part Of: Oral diseases. Volume 23:Number 4(2017)
• Page Start: 477
• Page End: 483
• Publication Date: 2017-03-06
• Subjects: jaw osteonecrosis -- bisphosphonates -- breast cancer -- multiple myeloma -- prostate cancer -- osteoporosis; Mouth -- Diseases -- Research -- Periodicals; 617.522
• DOI: 10.1111/odi.12632
• Languages: English
• ISSNs: 1354-523X

Abstract

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.