Periodontal Disease as a Risk Factor for ONJ

描述（由申请人提供）：颌骨骨坏死（ONJ）是最近描述的长期双膦酸盐（BP）治疗的主要并发症。BP是骨吸收的有效抑制剂，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症。大多数患者表现为一侧或两侧颌骨疼痛性无血管骨暴露，模拟“牙痛”或骨感染。目前，对于ONJ没有有效的治疗方法。牙周病是ONJ的常见危险因素。然而，大多数关于这些危险因素的信息都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关联。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，以检验牙周疾病和牙周病原体是接受静脉内BP的癌症患者ONJ的危险因素这一假设。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ONJ静脉内BP的癌症患者和100名对照（根据癌症类型、BP类型、BP持续时间、年龄和性别匹配的静脉内BP的癌症患者，未发生ONJ）。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发生风险之间的关系。我们将对病例和对照组进行彻底的口内和牙周检查，以检测牙周炎的临床指标是否与ONJ相关。此外，我们还将评估从这些相同的病例和对照组中收集的龈下菌斑样本中假定牙周病原体的患病率。(b)确定ONJ是否与牙周致病菌和放线菌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是否定植在ONJ病变附近的口腔粘膜细胞中并促进其发展。研究结果将用于确定牙周病在ONJ发病机制中的作用，并有助于预防和干预策略的发展。 公共卫生相关性：静脉注射双膦酸盐是多发性骨髓瘤、乳腺癌和前列腺癌骨转移患者治疗方案的常规组成部分，因为它们能够减少癌症引起的骨破坏。颌骨骨坏死是最近发现的双磷酸盐治疗的破坏性不良反应。在这个探索性的建议中，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.