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Updates on osteonecrosis of the jaw.

ABSTRACT: PURPOSE OF REVIEW:Osteonecrosis of the jaw (ONJ) is an uncommon condition noted to occur in patients with cancer who are receiving intravenous bisphosphonates. The cause of ONJ remains unknown. The leading hypotheses addressing the mechanism of ONJ are reviewed here. RECENT FINDINGS:The present clinical data suggest that ONJ may occur in approximately 5% of patients with metastatic bone disease. The ability to predict an individual's risk of developing ONJ remains elusive. It is likely that an altered bone microenvironment and/or host defense mechanisms effected by medications used to treat patients with metastatic bone disease contributes to the development of ONJ. Medications that significantly reduce osteoclastic activity are associated with ONJ. Preclinical models of ONJ are being developed but to establish such an intricate systemic condition in animals is challenging. SUMMARY:The ONJ field has progressed via knowledge gained by case reports, population-based studies, and emerging animal models. Still, there are myths that need to be resolved and important clues that need to be investigated. Understanding the pathophysiology of this condition will be critical to improve patient care. Communications between oncologists, dentists, basic scientists, and patients are central to effective treatment and research for this condition.

SUBMITTER: Yamashita J

PROVIDER: S-EPMC2962852 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Updates on osteonecrosis of the jaw.

Yamashita Junro J McCauley Laurie K LK Van Poznak Catherine C

Current opinion in supportive and palliative care 20100901 3

<h4>Purpose of review</h4>Osteonecrosis of the jaw (ONJ) is an uncommon condition noted to occur in patients with cancer who are receiving intravenous bisphosphonates. The cause of ONJ remains unknown. The leading hypotheses addressing the mechanism of ONJ are reviewed here.<h4>Recent findings</h4>The present clinical data suggest that ONJ may occur in approximately 5% of patients with metastatic bone disease. The ability to predict an individual's risk of developing ONJ remains elusive. It is l ...[more]

PMID: 20657284

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Project description:ObjectiveThe purpose of this study was to provide a cross-sectional view of all registered clinical trials enrolling patients with osteonecrosis of the jaw (ONJ). The primary aim was to report predictors of trial completion and publication of results.Materials and methodsThis is a cross-sectional study of ONJ trials registered with ClinicalTrials.gov. For each included entry, trial characteristics and endpoints were recorded. Predictors were enrollment size, etiology, study type, intervention type, sponsor, funding, study locations, number of centers, and specialty of the principal investigator. Outcomes were trial status, publication on PubMed, journal of publication, and length of time between endpoints. Associations between predictors and outcomes were evaluated using chi-square tests and t-tests.ResultsThe final sample included 26 trials. Overall, 50% of trials were completed and 69% of completed trials were published. Three out of four terminated trials were suspended due to lack of funding. The median enrollment for completed trials was 149 participants with a mean length of five years. All trials included medication-related osteonecrosis of the jaw (MRONJ) patients and 26% also included osteoradionecrosis of the jaw (ORNJ) patients. The majority of trials were observational (65%), conducted internationally (62%), and involved multiple centers (54%). Published trials had a mean time of 5.9 years between trial start and publication, which was comparable to trial length (p=0.90) and appeared in either dental (44%) or cancer (56%) journals. Completion and publication rates were not significantly increased by industry sponsorship/funding, larger enrollment sizes, or multi-center involvement. Oral and maxillofacial surgery was the most represented dental specialty of principal investigators (56%).ConclusionsThe majority of completed ONJ trials had their results published in a timely manner. Evidence-based investigation of ONJ is a multi-disciplinary and international effort. Among all specialists, oral and maxillofacial surgeons led the most ONJ trials.

Project description:Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse event affecting patients with cancer and patients with osteoporosis who have been treated with powerful antiresorptives (pARs) or angiogenesis inhibitors (AgIs). pARs, including nitrogen-containing bisphosphonates (N-BPs; e.g., zoledronic acid, alendronate) and anti-RANKL antibodies (e.g., denosumab), are used to manage bone metastases in patients with cancer or to prevent fragility fractures in patients with osteoporosis. Though significant advances have been made in understanding MRONJ, its pathophysiology is still not fully elucidated. Multiple species have been used in preclinical MRONJ research, including the rat, mouse, rice rat, rabbit, dog, sheep, and pig. Animal research has contributed immensely to advancing the MRONJ field, particularly, but not limited to, in developing models and investigating risk factors that were first observed in humans. MRONJ models have been developed using clinically relevant doses of systemic risk factors, like N-BPs, anti-RANKL antibodies, or AgIs. Specific local oral risk factors first noted in humans, including tooth extraction and inflammatory dental disease (e.g., periodontitis, periapical infection, etc.), were then added. Research in rodents, particularly the rat, and, to some extent, the mouse, across multiple laboratories, has contributed to establishing multiple relevant and complementary preclinical models. Models in larger species produced accurate clinical and histopathologic outcomes suggesting a potential role for confirming specific crucial findings from rodent research. We view the current state of animal models for MRONJ as good. The rodent models are now reliable enough to produce large numbers of MRONJ cases that could be applied in experiments testing treatment modalities. The course of MRONJ, including stage 0 MRONJ, is characterized well enough that basic studies of the molecular or enzyme-level findings in different MRONJ stages are possible. This review provides a current overview of the existing models of MRONJ, their more significant features and findings, and important instances of their application in preclinical research.

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Updates on osteonecrosis of the jaw.

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Updates on osteonecrosis of the jaw.

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