Periodontal Disease as a Risk Factor for ONJ

牙周病是 ONJ 的危险因素

• 批准号: 7788281
• 负责人: RAJARAM GOPALAKRISHNAN
• 金额: $ 22.22万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7788281
• 关键词: Ache; Actinobacillus actinomycetemcomitans; Actinobacteria class; Actinomyces; Adverse effects; Age; Biology; Biometry; Bone Resorption; Bone necrosis; Breast; Cancer Patient; Case Series; Case Study; Case-Control Studies; Cells; Clinical; Clinical Research; Complication; Development; Enrollment; Environment; Epidemiology; Epithelial Cells; Fluorescent in Situ Hybridization; Forsythia; Functional disorder; Future; Goals; Hypercalcemia of Malignancy; Intervention; Intravenous; Invaded; Jaw; Knowledge; Lesion; Literature; Malignant Neoplasms; Malignant neoplasm of prostate; Matched Case-Control Study; Measures; Metastatic Neoplasm to the Bone; Modality; Molecular; Multiple Myeloma; Oral; Oral mucous membrane structure; Osteomyelitis; Osteoporosis; Pain; Pathogenesis; Pathology; Patients; Periodontal Diseases; Periodontitis; Population Control; Porphyromonas gingivalis; Predisposing Factor; Prevalence; Preventive Intervention; Prevotella intermedia; Prospective Studies; Reporting; Research; Research Personnel; Risk; Risk Factors; Role; Sampling; Simulate; Site; Solid Neoplasm; Testing; Therapeutic; Tooth structure; Treatment Protocols; Treponema denticola; Work; bisphosphonate; bone; cancer type; case control; design; effective therapy; expectation; inhibitor/antagonist; insight; maxillofacial; pathogen; prospective; public health relevance; sex; theories; Ache; Actinobacillus actinomycetemcomitans; Actinobacteria class; Actinomyces; Adverse effects; Age; Biology; Biometry; Bone Resorption; Bone necrosis; Breast; Cancer Patient; Case Series; Case Study; Case-Control Studies; Cells; Clinical; Clinical Research; Complication; Development; Enrollment; Environment; Epidemiology; Epithelial Cells; Fluorescent in Situ Hybridization; Forsythia; Functional disorder; Future; Goals; Hypercalcemia of Malignancy; Intervention; Intravenous; Invaded; Jaw; Knowledge; Lesion; Literature; Malignant Neoplasms; Malignant neoplasm of prostate; Matched Case-Control Study; Measures; Metastatic Neoplasm to the Bone; Modality; Molecular; Multiple Myeloma; Oral; Oral mucous membrane structure; Osteomyelitis; Osteoporosis; Pain; Pathogenesis; Pathology; Patients; Periodontal Diseases; Periodontitis; Population Control; Porphyromonas gingivalis; Predisposing Factor; Prevalence; Preventive Intervention; Prevotella intermedia; Prospective Studies; Reporting; Research; Research Personnel; Risk; Risk Factors; Role; Sampling; Simulate; Site; Solid Neoplasm; Testing; Therapeutic; Tooth structure; Treatment Protocols; Treponema denticola; Work; bisphosphonate; bone; cancer type; case control; design; effective therapy; expectation; inhibitor/antagonist; insight; maxillofacial; pathogen; prospective; public health relevance; sex; theories

DESCRIPTION (provided by applicant): Osteonecrosis of the jaw (ONJ) is a recently described major complication of long-term bisphosphonate (BP) treatment. BPs are potent inhibitors of bone resorption used in the treatment of multiple myeloma, skeletal metastases of solid tumors, hypercalcemia of malignancy and osteoporosis. Most patients present with painful exposed avascular bone in either or both jaws that simulates "tooth-ache" or bone infection. Currently, there is no effective treatment for ONJ. Periodontal disease is a commonly reported risk factor for ONJ. However, most of the information about these risk factors has been obtained through case reports, and there is an immediate need for matched case-control and prospective studies to confirm this association. The overall goal of current exploratory proposal is to perform a matched case-control study to test the hypothesis that periodontal disease and periodontal pathogens are risk factors for ONJ in cancer patients receiving intravenous BPs. To test our hypothesis and accomplish our goal, we plan to enroll 50 cancer patients receiving intravenous BP with ONJ and 100 controls (cancer patients on intravenous BP who have not developed ONJ) matched according to type of cancer, type of BP, duration of BP, age and sex. Two specific aims will be pursued. (a) To determine the association between clinical and microbiological measures of periodontitis and risk of ONJ development. We will perform a thorough intraoral and periodontal exam in cases and matched controls to test if clinical measures of periodontitis are associated with ONJ. Further, we will also evaluate the prevalence of putative periodontal pathogens in subgingival plaque samples collected from these same cases and controls. (b) To determine whether ONJ is associated with increased mucosal invasion of putative periodontal pathogens and Actinomyces species. We will evaluate if putative periodontal pathogens and Actinomyces species colonize the oral mucosa cells near the ONJ lesion and contribute to its development. The findings will be used to define the role of periodontal disease in ONJ pathogenesis and contribute towards development of prevention and intervention strategies. PUBLIC HEALTH RELEVANCE: Intravenous bisphosphonates are routine components of treatment protocols for multiple myeloma, and breast and prostate cancer patients with bone metastasis due to their ability to reduce cancer-induced destruction of bone. Osteonecrosis of the jaw is a recently identified devastating adverse effect of bisphosphonate treatment. In this exploratory proposal we will evaluate whether periodontal disease is a risk factor in osteonecrosis of jaw.

描述（由申请人提供）：颌骨（ONJ）的骨坏死是最近描述的长期双膦酸盐（BP）治疗的主要并发症。 BPS是用于治疗多发性骨髓瘤，实体瘤的骨骼转移，恶性肿瘤和骨质疏松症的有效抑制剂。大多数患者都在模拟“牙齿痛”或骨骼感染的两种颌骨中出现疼痛的裸露血管骨。目前，尚无有效的ONJ治疗方法。牙周疾病是ONJ的常见危险因素。但是，有关这些危险因素的大多数信息都是通过案例报告获得的，并且迫切需要进行匹配的病例对照和前瞻性研究以确认该关联。当前探索性建议的总体目标是进行匹配的病例对照研究，以检验以下假设：牙周疾病和牙周病原体是接受静脉内BPS的癌症患者的ONJ的危险因素。为了检验我们的假设并实现我们的目标，我们计划招募50名接受静脉注射BP的癌症患者，并根据癌症类型，BP类型，BP的持续时间，BP，年龄和性别匹配。将追求两个具体的目标。 （a）确定牙周炎的临床和微生物学测量与ONJ发育风险之间的关联。我们将在情况下进行彻底的口腔内和牙周检查，并进行匹配的对照，以测试牙周炎的临床测量是否与ONJ相关。此外，我们还将评估从这些情况和对照组中收集的尺寸斑块样品中推定牙周病原体的患病率。 （b）确定ONJ是否与假定的牙周病原体和放线菌种类的粘膜侵袭增加有关。我们将评估假定的牙周病原体和放线菌种类是否在ONJ病变附近定居于口腔粘膜细胞并为其发育做出贡献。这些发现将用于定义牙周疾病在ONJ发病机理中的作用，并有助于发展预防和干预策略。 公共卫生相关性：静脉双膦酸盐是多发性骨髓瘤的治疗方案的常规组成部分，由于其能够减少癌症引起的骨骼破坏的能力，因此具有骨转移的乳腺和前列腺癌患者。颌骨的骨坏死是双膦酸盐处理的毁灭性不良影响。在此探索性建议中，我们将评估牙周疾病是否是颌骨骨坏死的危险因素。