Bisphosphonates and Oral Complications of Cancer Chemotherapy: A Pilot Study

双膦酸盐与癌症化疗的口腔并发症：一项试点研究

• 批准号: 7282675
• 负责人: REGINA LANDESBERG
• 金额: $ 19.54万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7282675
• 关键词: Affect; Age; Angiogenic Factor; Biological Markers; Blood Cells; Blood Coagulation Disorders; Bone Resorption; Bone necrosis; Breast; Cancer Patient; Case-Control Studies; Chemistry; Chemotherapy-Oncologic Procedure; Cohort Studies; Complication; Condition; Dental; Dental Hygiene; Development; Disseminated Malignant Neoplasm; Event; Future; Hypercalcemia of Malignancy; Incidence; Intravenous; Jaw; Lesion; Maintenance; Malignant Neoplasms; Malignant neoplasm of lung; Mental Depression; Metastatic Neoplasm to the Bone; Multiple Myeloma; Natural History; Neoplasm Metastasis; Numbers; Operative Surgical Procedures; Oral; Osteoporosis; Pathogenesis; Patient Care; Patients; Pharmaceutical Preparations; Pilot Projects; Prevention; Prospective Studies; Prostate; Rate; Reporting; Research Design; Risk; Risk Factors; Secondary to; Series; Serum; Skeletal system; Testing; Tooth Diseases; Tooth Extraction; Treatment Protocols; base; bisphosphonate; bone; bone imaging; bone turnover; case control; chemotherapy; inhibitor/antagonist; malignant breast neoplasm; prospective

DESCRIPTION (provided by applicant): Bisphosphonates (BPs) are potent inhibitors of bone resorption currently used in the treatment of osteoporosis, hypercalcemia of malignancy, multiple myeloma, and bone metastases associated with, breast, prostate, and lung cancer. In 2003, Marx reported 36 patients receiving intravenous BPs who developed unusual lesions of exposed bone in the jaws. Thirty five of these patients were concurrently receiving chemotherapy for cancer. Subsequently, Ruggiero et al. reported 63 patients with similar lesions of the jaws. In their series, 56 patients were under treatment for various malignancies and 7 patients were receiving therapy for osteoporosis. Intravenous BPs had been administered to all patients. Many, but not all patients had dental extractions or surgical manipulation prior to the development of osteonecrosis (ON). While it appears likely that an association of ON with BP therapy exists, scientifically-based studies are critical in order to define the pathogenesis and natural history of this condition. Although BPs is currently utilized in the treatment of a limited number of conditions, the potential for these drugs to be used in many other applications is vast. It is therefore critical to future patient care to identify risk factors and candidate markers for the development of jaw ON. This proposal will describe a case controlled, cross-sectional as well as a prospective longitudinal pilot study of a well defined group of breast cancer patients being treated with chemotherapy. The case controlled study will evaluate patients who present with ON. Age and ethnically matched patients without ON from the prospective study will be compared to affected patients in order to identify local and systemic abnormalities that are associated with this condition. The prospective study will examine two groups of 200 breast cancer patients on maintenance chemotherapy, with one group receiving BPs for the treatment of skeletal related events secondary to bone metastases. We will examine a number of risk factors including oral hygiene, the presence of dental disease, early radiographic findings, bone turnover, coagulopathies, depression of serum angiogenesis factors, and alteration of blood cells or serum chemistry to determine if we can predict which patients will develop this condition. The findings will be used to define the natural history, risk factors, and candidate markers for the development of jaw osteonecrosis and allow future development of rational prevention and treatment regimens.

描述（由申请人提供）：双膦酸盐（BPS）是目前用于治疗骨质疏松症，恶性肿瘤高钙血症，多发性骨髓瘤和与，乳腺癌，前列腺癌和肺癌相关的骨吸收的有效抑制剂。 2003年，马克思报告说，有36名患者接受了静脉注射BPS，这些患者在颌骨中出现了异常的暴露骨骼病变。这些患者中有35例同时接受癌症化疗。随后，Ruggiero等。报告了63例颌骨病变类似的患者。在他们的系列中，有56例患者正在接受各种恶性肿瘤治疗，7例患者接受了骨质疏松症的治疗。静脉注射BP已向所有患者施用。许多（但并非所有患者）在发生截骨性（ON）之前都进行了牙齿提取或手术操纵。尽管ON与BP疗法的关联似乎很可能存在，但基于科学的研究对于定义这种情况的发病机理和自然历史至关重要。尽管目前BPS用于治疗有限数量的疾病，但这些药物在许多其他应用中使用的可能性很大。因此，对于未来的患者护理而言，要识别出下颌开发的危险因素和候选标志物至关重要。该提案将描述一项受到控制的病例，横断面以及一项针对化学疗法治疗良好定义的乳腺癌患者组的前瞻性纵向试验研究。案例对照研究将评估出现在ON的患者。将前瞻性研究的年龄和种族匹配的患者与受影响的患者进行比较，以识别与这种情况相关的局部和全身异常。这项前瞻性研究将检查两组200名乳腺癌患者的维持化疗，其中一组接受BPS用于治疗骨骼转移继发的骨骼相关事件。我们将检查许多危险因素，包括口腔卫生，牙齿疾病的存在，早期的射线照相发现，骨骼更新，凝血病，血清血管生成因子的抑郁症以及血细胞或血清化学的改变，以确定我们是否可以预测哪些患者是否会发展此疾病。这些发现将用于定义自然史，危险因素和候选标志物的发展，以开发颌骨的发生，并允许未来发展理性预防和治疗方案。