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 7 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 cancer patients treated with zoledronate. Accepted ArticleThis article is protected by copyright. All rights reserved. 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 of 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.

Effects of Zoledronic Acid in Experimental Periapical Lesions in Rats: An Imaging and Histological Analysis

“…These drugs have high affinity for bone tissue and act by inhibiting the activity of osteoclasts and consequently, the bone resorption (1)(2)(3). Similar to pyrophosphate, the BP bind strongly to the hydroxyapatite crystals.…”

“…The synthesis of OPG leads to a decreasing in osteoclastic activity (5). Because of their anti-resorptive action, BP are used in the treatment of bone diseases, such as osteoporosis, osteopenia, Paget disease, hypercalcemia associated with cancer, multiple myeloma, and bone metastases (1)(2)(3).…”

“…BRONJ is characterized by necrosis of the mandible or maxilla in patients taking bisphosphonates (BP) and not exposed to radiotherapy in the head and neck region (1). BP are used in the treatment of bone diseases, such as osteoporosis, osteopenia, Paget disease, hypercalcemia associated with cancer, multiple myeloma, and bone metastases (1)(2)(3). Studies have shown some risk factors that are significant for the development of BRONJ, such as type of BP, route of administration (oral or endovenous), number of infusions, age and dental extractions (1)(2)(3).…”

“…BP are used in the treatment of bone diseases, such as osteoporosis, osteopenia, Paget disease, hypercalcemia associated with cancer, multiple myeloma, and bone metastases (1)(2)(3). Studies have shown some risk factors that are significant for the development of BRONJ, such as type of BP, route of administration (oral or endovenous), number of infusions, age and dental extractions (1)(2)(3). BRONJ usually occurs after an invasive dental procedure, but it can also happen spontaneously (6).…”

Efeito da terapia de longa duração com ácido zoledrônico no osso esponjoso da mandíbula e fêmur de ratos Wistar

“…; Fraturas atípicas do fêmur (FAF) e osteonecrose dos maxilares associada ao uso de bisfosfonatos; OMAB) (RUSSELL, 2011;FUNG et al, 2016). A principal preocupação em relação ao uso prolongado dos BF está relacionada à possibilidade de supressão excessiva da remodelação óssea que pode prejudicar a força óssea e a resposta às lesões locais (RUSSELL, 2011;LIU et al, 2014).…”