58 research outputs found

    Zoledronic acid inhibits macrophage SOCS3 expression and enhances cytokine production

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    Suppressor of cytokine signaling‐3 (SOCS3) has multiple functions including inhibition of Janus kinase (Jak) activity, regulation of protein degradation, and suppression of cytokine signaling. SOCS3 modulates macrophage response to cytokines such as IL‐6 and leptin that are systemically induced in obesity. Obesity is a suspected risk factor for SOCS3‐related pathology such as rheumatoid arthritis and Crohn's disease as well as zoledronic acid (ZA)‐induced osteonecrosis of the jaw (ONJ). Thus, understanding the ability of bisphosphonates to modulate SOCS3 is necessary to qualify their contribution to these disorders. ONJ occurs in up to 10% of patients using intravenous bisphosphonates and has an unknown pathogenesis that may be linked to decreased bone turnover, altered vascularity, bacterial invasion, and compromised wound healing. Given the increased risk of ONJ with obesity and importance of macrophages in wound healing, we hypothesized that amino‐bisphosphonates could contribute to the pathogenesis of ONJ by regulating macrophage responses to cytokines such as leptin and IL‐6. We report that ZA is a novel inhibitor of SOCS3 in primary macrophages and human ONJ biopsy specimens. Inhibition of SOCS3 by ZA resulted in significant increases in IL‐6 production. SOCS3 transcription is regulated by nuclear accumulation of phosphorylated‐Stat3 (P‐Stat3). We found that ZA decreased phosphorylation of Stat3 in a mevalonate‐pathway dependent manner. However, restoration of P‐Stat3 was not sufficient to correct SOCS3 inhibition. We propose that disruption of macrophage SOCS3 expression by amino‐bisphosphonates such as ZA may be a novel contributor to inflammatory phenotypes in obesity and the pathogenesis of ONJ. J. Cell. Biochem. 112: 3364–3372, 2011. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87102/1/23267_ftp.pd

    Oral cancer treatment costs in Greece and the effect of advanced disease

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    BACKGROUND: The main purpose of the study was to quantify the direct costs of oral cancer treatment to the healthcare system of Greece. Another aim was to identify factors that affect costs and potential cost reduction items. More specifically, we examined the relationship between stage of disease, modality of treatment and total direct costs. METHODS: The medical records and clinic files of the Oral and Maxillofacial Clinic of the Athens General Hospital "Genimatas" were abstracted to investigate clinical treatment characteristics, including length of hospitalization, modes of treatment, stage of disease etc. Records of 95 patients with oral squamous cell carcinoma (OSSC), with at least six months of follow-up, were examined. The clinical data was then used to calculate actual direct costs, based on 2001 market values. RESULTS: The mean total direct costs for OSSC treatment estimated at euro 8,450 or approximately US$ 7,450. Costs depended on the stage of the disease, with significant increases in stages III and IV, as compared with stages I and II (p < 0.05). Multi-modality treatment applied mainly to patients in stages III and IV was the factor that affected the cost. Disease stage was also associated with the total duration of hospitalization (p < 0.05). CONCLUSIONS: The clinical management of advanced oral cancer is strongly associated with higher costs. Although the ideal would be to prevent cancer, the combination of high-risk screening, early diagnosis and early treatment seems the most efficient way to reduce costs, and most importantly, prolong life

    Delayed woundhealing after tooth extraction and self–reportedkyphosis in Japanese men and women

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    It is unclear whether osteoporosis itself is a main risk factor for delayed wound healing after tooth extraction in humans. In this study, we evaluated the association between experience of delayed wound healing after last tooth extraction and self-reported kyphosis, with the possibility of having vertebral fractures, in Japanese patients. Among the 1,504 patients who responded to the structured questionnaire survey, 518 patients (134 men and 384 women) aged 55-97 years finally participated in this study. Patients who self-reported mild-moderate kyphosis were more likely to have problematic delayed wound healing after last tooth extraction than those who reported severe kyphosis (odds ratio [OR] 4.98; 95% confidence interval [CI], 1.86-13.38 and OR 2.30; 95% CI, 0.52-10.22, respectively) (p for trend = 0.005). Japanese patients with vertebral fractures may have a higher risk of having problematic delayed wound healing after tooth extraction

    Residents' journal review

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    Closing in on the Puzzle of ONJ

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    Bisphosphonates and Time to Osteonecrosis Development

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    Abstract Learning Objectives After completing this course, the reader will be able to: Evaluate the current state of knowledge regarding risk of osteonecrosis of the jaw as it relates to dose and duration of intravenous bisphosphonates.Explain the concept of risk assessment in the context of preventing the development of osteonecrosis of the jaw.Describe the pathophysiology of ONJ and outline contributing factors such as invasive dental procedures, comorbidities, concomitant medications, vitamin D deficiency and/or hyperparathyroidism, certain genotypes, smoking, and the role of obesity. This article is available for continuing medical education credit at CME.TheOncologist.com. Bisphosphonate-associated osteonecrosis of the jaw (BONJ) is a complication of long-term bisphosphonate (BP) use. Given the beneficial effects of BP on bone quality in patients with cancer or osteoporosis, it is of great importance to understand the risk as it relates to time to event or cumulative dose until the onset of disease. Because there is no information on the lowest toxic dose from clinical trials, here we report on a review of 71 case series published since 2003. We calculated the weighted mean time to event, as well as the minimum reported time and dose for zoledronate, pamidronate, and oral bisphosphonates. The mean time to BONJ after zoledronate treatment was calculated at 1.8 years and the minimum was 10 months; after pamidronate, the mean time was 2.8 years and the minimum was 1.5 years; and after oral BP therapy, the mean time was 4.6 years and the minimum was 3 years. Zoledronic acid seems to be the most potent among the nitrogen-containing BPs. Factors that seem to affect BONJ and time to event were invasive dental procedures and other comorbid factors such as advanced age, rheumatoid arthritis, diabetes, use of corticosteroids, vitamin D deficiency, and more. Understanding the pathophysiology of the disease requires further research. </jats:sec
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