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Minden, Germany

Kos M.,Klinikum Minden
Medical Hypotheses | Year: 2011

A specific chemical structure of bisphosphonates (BPs) determines their ability to inhibit bone resorption. Because of that they have been successfully used for several years to treat skeletal events in neoplasia, hypercalcemia of malignancy, osteoporosis, Paget's disease, osteogenesis imperfecta and fibrous dysplasia. Recently, bisphosphonate related osteonecrosis of the jaws (BRONJ) has been reported as a serious complication of therapy with these compounds. According to the currently recognised theory of its origin arrest of the osteoclast function not only reflects in diminished bone resorption, but also in reduced bone formation, both leading to decreased bone turnover and consequently to the bone necrosis.A novel hypothesis assumes that BRONJ is supported by increased bacterial adhesion to bone coated with BPs. It could be mediated by proteins termed "microbial surface components which recognise adhesive matrix molecules" (MSCRAMM). It has been found that binding of Gram-positive strains was due to the amino-terminal domain of MSCRAMM structure and that this interaction played significant role in the pathogenesis of infection. The cationic amino group of nitrogen containing BPs may attract bacteria by direct electrostatic interaction, through a direct surface protein interaction or by providing an amino acid mimic on the surface of the bony hydroxyapatite which interacts with MSCRAMM component and mediates increased bacterial adhesion. Bone exposition during dental surgical procedures acts as a trigger opening the door for bacterial invasion. That is why a strong correlation between BRONJ and dental surgical procedures exists. The jaw bones are especially subjected to infection due to thin epithelial line coating their surface, susceptibility to trauma, and presence of teeth. © 2011 Elsevier Ltd.

Introduction: The aim of this study was to establish the incidence of bi-sphosphonate-related osteonecrosis of the jaws (BRONJ) in oncologic patients and to determine risk predictors with respect to this condition. Material and methods: This retrospective review included 197 oncologic patients treated from January 2005 to December 2010 with administration of bisphosphonates (BPs) as part of management. Sex, age, type of cancer diagnosed, period of substantial disease, oral surgery, type of bisphosphonate, number of doses, and cases of BRONJ diagnosis were recorded. The cumulative incidence and incidence rate of BRONJ were calculated. The factors that influenced BRONJ were assessed with multivariate logistic regression and with estimations of 95% confidence intervals and odd ratios. Values of p ≤ 0.05 were considered significant. Results: The BRONJ appeared in 9.64% of patients. The BRONJ incidence rate was 1 in 28 patients per year of BP treatment. Logistic regression showed that the odds of osteonecrosis increased 1.0172-fold with each given dose of BP. The BRONJ risk with zoledronate was 5-fold higher than that with pamidronate or ibandronate. The risk of BRONJ increased by 40-fold after dental surgery. Conclusions: Period of BP administration and type of BP used are important risk predictors for the development of BRONJ in oncologic patients treated with intravenous administration of these drugs. Patient-related factors are dental or periodontal events connected with need for oral surgery. Copyright © 2015 Termedia & Banach.

Rollig C.,Universitatsklinikum Dresden | Thiede C.,Universitatsklinikum Dresden | Gramatzki M.,Universitatsklinikum Schleswig Holstein | Aulitzky W.,Robert Bosch GmbH | And 15 more authors.
Blood | Year: 2010

We present an analysis of prognostic factors derived from a trial in patients with acute myeloid leukemia older than 60 years. The AML96 trial included 909 patients with a median age of 67 years (range, 61-87 years). Treatment included cytarabine-based induction therapy followed by 1 consolidation. The median follow-up time for all patients is 68 months (5.7 years). A total of 454 of all 909 patients reached a complete remission (50%). Five-year overall survival (OS) and disease-free survival were 9.7% and 14%, respectively. Multivariate analyses revealed that karyotype, age, NPM1 mutation status, white blood cell count, lactate dehydrogenase, and CD34 expression were of independent prognostic significance for OS. On the basis of the multivariate Cox model, an additive risk score was developed that allowed the subdivision of the largest group of patients with an intermediate-risk karyotype into 2 groups. We are, therefore, able to distinguish 4 prognostic groups: favorable risk, good intermediate risk, adverse intermediate risk, and high risk. The corresponding 3-year OS rates were 39.5%, 30%, 10.6%, and 3.3%, respectively. The risk model allows further stratification of patients with intermediate-risk karyotype into 2 prognostic groups with implications for the therapeutic strategy. This study was registered at www.clinicaltrials.gov as #NCT00180115. © 2010 by The American Society of Hematology.

Introduction: To assess the association of oral hygiene, dental caries, and periodontal status with bisphosphonate-related osteonecrosis of the jaws. Material and methods: A retrospective case-control study on 81 patients treated for neoplasms with bone metastases. Twenty-nine patients with bone necrosis and 52 controls treated with bisphosphonates were compared using the Oral Hygiene Index, Decay, Missing, Filled Teeth, Community Periodontal Index of Treatment Needs, and Residual Periodontal Bone. The null hypothesis stated that there was no difference in parameters of oral health between patients with and without bone necrosis. Differences of means of above-mentioned variables were compared between the groups with Student's t-test or Mann-Whitney rank sum test and χ2 test. Value of p . 0.05 was considered significant. Results: Poorer oral hygiene (OHIs 1.94 vs. 1.32; p = 0.065), more advanced dental caries (DMFT 26.85 vs. 22.87; p = 0.05), and more advanced periodontal disease (CPITN: = 0: 21.05% vs. 42.51%; = 1 13.16% vs. 7.29%; = 2: 0% vs. 15.38%; = 3: 65.79% vs. 28.34%; = 4: 0% vs. 6.48%, Residual periodontal bone 73.1% vs. 80.51%; p = 0,001) were characteristic of patients with bisphosphonate related jaw necrosis when compared with control group. An advanced dental caries or periodontal disease required surgical intervention which directly contributed to the development of the bone necrosis. Conclusions: Dental and periodontal disease can lead to bisphosphonate-related osteonecrosis of the jaw. Oncologic patients treated with bisphosphonates should be offered preventive care to reduce dental plaque, calculus, dental caries, and periodontal disease.

Wilson P.W.F.,Emory University | D'Agostino Sr. R.,Boston University | Bhatt D.L.,Harvard University | Eagle K.,University of Michigan | And 12 more authors.
American Journal of Medicine | Year: 2012

BACKGROUND: Prediction models for cardiovascular events and cardiovascular death in patients with established cardiovascular disease are not generally available. METHODS: Participants from the prospective REduction of Atherothrombosis for Continued Health (REACH) Registry provided a global outpatient population with known cardiovascular disease at entry. Cardiovascular prediction models were estimated from the 2-year follow-up data of 49,689 participants from around the world. RESULTS: A developmental prediction model was estimated from 33,419 randomly selected participants (2394 cardiovascular events with 1029 cardiovascular deaths) from the pool of 49,689. The number of vascular beds with clinical disease, diabetes, smoking, low body mass index, history of atrial fibrillation, cardiac failure, and history of cardiovascular event(s) <1 year before baseline examination increased risk of a subsequent cardiovascular event. Statin (hazard ratio 0.75; 95% confidence interval, 0.69-0.82) and acetylsalicylic acid therapy (hazard ratio 0.90; 95% confidence interval, 0.83-0.99) also were significantly associated with reduced risk of cardiovascular events. The prediction model was validated in the remaining 16,270 REACH subjects (1172 cardiovascular events, 494 cardiovascular deaths). Risk of cardiovascular death was similarly estimated with the same set of risk factors. Simple algorithms were developed for prediction of overall cardiovascular events and for cardiovascular death. CONCLUSIONS: This study establishes and validates a risk model to predict secondary cardiovascular events and cardiovascular death in outpatients with established atherothrombotic disease. Traditional risk factors, burden of disease, lack of treatment, and geographic location all are related to an increased risk of subsequent cardiovascular morbidity and cardiovascular mortality. © 2012 Elsevier Inc. All rights reserved.

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