CROHNS DISEASE AND OSTEOPENIA--BASIC PATHOGENIC MECHANISMS

克罗恩病与骨质减少--基本发病机制

• 批准号: 6122692
• 负责人: FRANCISCO A SYLVESTER
• 金额: $ 1.91万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6122692
• 关键词: Crohn's disease; biomarker; bone density; bone metabolism; calcium metabolism; clinical research; cytokine; dosage; gastrointestinal disorder chemotherapy; human subject; human therapy evaluation; osteopenia; pathologic process

Recruitment of patients was initiated at Connecticut Children's Medical Center in Hartford, CT and at the Hospital for Sick Children in Toronto. To date, 28 patients with inflammatory bowel disease have been recruited. We are on target to reach our goal of recruitment for Crohn's disease and ulcerative colitis patients. We are now focusing our recruitment efforts on normal controls and "inflammatory" (rheumatologic) controls. Our preliminary results of bone density indicate that approximately 50% of children with Crohn's disease have osteopenia at least in one site (lumbar spine, hip, total body) at the time of diagnosis. In addition, patients recruited in Toronto are also undergoing radiological bone density measurements with heel ultrasonography. So far, there is a 100% correlation between DEXA and ultrasonographic determination of osteopenia. These observations support our hypothesis that the inflammatory process underlying Crohn's disease affects bone homeostasis, leading to osteopenia. We will correlate bone density scores with data on biochemical markers of bone formation and bone resorption, disease activity, calcium intake and levels of cytokines at the end of the study to identify risk factors for osteopenia and osteoporosis. Our discoveries to date confirm the high frequency of osteopenia in patients with Crohn's disease. Our study will be the first large prospective longitudinal study measuring bone density and biochemical parameters of bone metabolism from time of diagnosis in children. This study is important because it avoids confounding variables encountered in cross-sectional studies. It also addresses the problem of bone loss in a particularly susceptible group of patients - children. The presence of osteopenia at a young age increases the lifetime risk of pathologic fractures and may affect linear growth. In addition, it is not clear whether Crohn's disease osteopenia improves with clinical remission. Therefore, it is of fundamental importance to understand the natural history and basic pathogenic mechanisms involved in Crohn's disease osteopenia. This knowledge will help to find specific therapies designed to treat osteopenia in Crohn's disease and perhaps other intestinal inflammatory conditions associated with bone loss.

在康涅狄格州哈特福德的康涅狄格州儿童医疗中心和多伦多病儿童医院招募患者。迄今为止，已招募了28例炎症性肠病患者。我们的目标是实现克罗恩病和溃疡性结肠炎患者的招募目标。 现在，我们将招聘工作集中在正常控制和“炎症”（风湿病）控制上。 我们的骨密度初步结果表明，诊断时，约有50％的克罗恩病儿童至少在一个部位（腰椎，臀部，全身）患有骨质减少症。 此外，多伦多招募的患者还通过脚跟超声检查进行放射线骨密度测量。 到目前为止，DEXA与骨质减少症的超声测定之间存在100％的相关性。这些观察结果支持我们的假设，即克罗恩病的炎症过程会影响骨稳态，从而导致骨质减少症。我们将将骨密度评分与研究结束时骨形成和骨吸收，疾病活性，钙摄入量和细胞因子水平的生化标志的数据相关联，以鉴定骨质骨质减少和骨质疏松症的危险因素。 迄今为止，我们的发现证实了克罗恩病患者的骨质减少症的高频。 我们的研究将是第一项大型前瞻性纵向研究，以测量儿童诊断时间从骨骼代谢的骨密度和生化参数。 这项研究很重要，因为它避免了在横断面研究中遇到的混淆变量。 它还解决了特别易感的患者 - 儿童的骨质流失问题。 骨质减少症在年轻时的存在会增加病理骨折的寿命风险，并可能影响线性生长。 此外，尚不清楚克罗恩病骨质减少症是否随着临床缓解而改善。因此，了解克罗恩病骨质减少症涉及的自然史和基本致病机制至关重要。 这些知识将有助于找到旨在治疗克罗恩病中骨质减少症的特定疗法，也许还有其他与骨质流失相关的肠道炎症疾病。