Periodontal Disease as a Risk Factor for ONJ

描述(由申请人提供)：颌骨坏死(ONJ)是最近描述的长期双磷酸盐(BP)治疗的主要并发症。BPS是一种有效的骨吸收抑制剂，用于治疗多发性骨髓瘤、实体瘤的骨转移、恶性肿瘤的高钙血症和骨质疏松。大多数患者出现一侧或两侧颌骨疼痛、裸露的无血管骨，表现为“牙痛”或骨感染。目前，ONJ还没有有效的治疗方法。牙周病是ONJ的常见危险因素。然而，关于这些危险因素的大部分信息是通过病例报告获得的，迫切需要匹配的病例对照和前瞻性研究来证实这种联系。目前探索性建议的总体目标是进行一项匹配的病例对照研究，以检验牙周病和牙周病原体是接受静脉注射BPS的癌症患者发生ONJ的危险因素的假设。为了验证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BP联合ONJ的癌症患者和100名对照(接受静脉BP的癌症患者没有发生ONJ)，根据癌症类型、BP类型、BP持续时间、年龄和性别进行匹配。我们将追求两个具体目标。(A)确定牙周炎的临床和微生物指标与ONJ发展风险之间的联系。我们将在病例和配对对照中进行彻底的口腔内和牙周检查，以测试牙周炎的临床措施是否与ONJ有关。此外，我们还将评估从这些相同的病例和对照中收集的牙周菌斑样本中可能存在的牙周病原体的流行率。(B)确定ONJ是否与可能的牙周病原体和放线菌物种的粘膜侵袭增加有关。我们将评估可能的牙周病原体和放线菌物种是否在ONJ病变附近的口腔粘膜细胞中定植并对其发展做出贡献。这些发现将被用来确定牙周病在ONJ发病机制中的作用，并有助于制定预防和干预策略。 公共卫生相关性：静脉注射双磷酸盐是多发性骨髓瘤以及乳腺癌和前列腺癌患者骨转移治疗方案的常规组成部分，因为它们有能力减少癌症引起的骨破坏。颌骨骨坏死是最近发现的一种双磷酸盐治疗的破坏性不良反应。在这个探索性方案中，我们将评估牙周病是否是颌骨骨坏死的危险因素。

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.