The Role of PTH in the Low Bone Mass of Anorexia Nervosa

PTH 在神经性厌食症低骨量中的作用

• 批准号: 8461456
• 负责人: Pouneh Khadejeh Fazeli
• 金额: $ 18.66万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8461456
• 关键词: Affect; Age; Anabolic Agents; Animal Model; Anorexia Nervosa; Area; Award; Biology; Biometry; Body Weight decreased; Bone Density; Bone Resorption; Caloric Restriction; Chronic; Clinical Research; Comorbidity; Complication; Data; Disease; Estrogens; FDA approved; Finite Element Analysis; Fracture; Functional disorder; Funding; General Hospitals; Glycoproteins; Goals; Grant; Hormonal; Hormones; Human; Insulin-Like Growth Factor I; Investigation; Lead; Malnutrition; Massachusetts; Master of Public Health; Measurement; Measures; Mechanics; Mediating; Medical; Medicine; Mentors; Methodology; Methods; Modeling; Morbidity - disease rate; Neuroendocrinology; Neurosecretory Systems; Nutritional; Osteocytes; Osteogenesis; Osteoporosis; Pathogenesis; Peripheral; Placebos; Population; Population Control; Positioning Attribute; Postmenopausal Osteoporosis; Postmenopause; Prevalence; Property; Prospective Studies; Proteins; Public Health Schools; Public Health Students; Randomized; Recovery; Relative (related person); Research; Research Design; Research Personnel; Resolution; Resources; Risk; Role; Starvation; Structure; Techniques; Teriparatide; Therapeutic; Thick; Time; Training; Weight; Woman; Women' s Group; aged; bone; bone loss; bone mass; bone strength; catalyst; college; deprivation; improved; inhibitor/antagonist; instructor; intervention effect; medical complication; medical schools; meetings; mortality; novel; nutrition; prevent; randomized placebo controlled trial; response; skills; translational study

DESCRIPTION (provided by applicant): Anorexia Nervosa (AN) affects 0.5-1% of college-aged women in the US and is characterized by extreme, self- induced starvation. Of the many medical co-morbidities associated with AN, severe bone loss is the most common and often persists despite weight recovery. This bone loss is significant because women with AN also have an increased fracture risk; a prospective study demonstrated that women with AN have a 7-fold increased risk of fractures as compared to age-matched controls. Therefore, a treatment to prevent the severe bone loss associated with AN is critical. There are currently no approved treatments for AN-associated bone loss. Therapies which prevent bone loss in normal-weight, hypogonadal women, such as estrogen, do not improve bone mineral density in women with AN. This is likely because the pathogenesis of bone loss due to nutritional deprivation differs from that of post-menopausal osteoporosis. In AN, there is a dramatic decrease in bone formation. Therefore an agent which stimulates bone formation would be an important potential treatment. Currently teriparatide (PTH) is the only anabolic agent approved by the FDA for the treatment of osteoporosis. As the effects of PTH on bone are known to be mediated through IGF-I and IGF-I levels are low in states of nutritional deficiency, we propose to investigate the effects of PTH on bone mass in women with AN. We will randomize thirty women with AN to treatment with either PTH or placebo and follow them prospectively for 6 months. We will measure bone mineral density, parameters of bone microarchitecture and bone strength at baseline and at 6 months. We will also measure markers of bone formation and resorption, IGF-I and sclerostin levels at baseline and monthly during the course of the study. Dr. Fazeli is an Instructor in Medicine at Harvard Medical School and Assistant in Medicine at Massachusetts General Hospital (MGH). She is on staff in the Neuroendocrine Unit at MGH and devotes the majority of her time to clinical research. Her expertise in studying hormonal abnormalities in AN positions her to lead the proposed project. She is well-supported by MGH and has full access to the Neuroendocrine Unit, Clinical Research Center and Harvard Catalyst CTSC resources. Her co-mentors, Drs. Anne Klibanski and Mary Bouxsein, are well-funded and invested in the direction of Dr. Fazeli's research. During the award period, Dr. Fazeli will obtain critical trainig in biostatistics and research design at the Harvard School of Public Health, where she is currently a Master of Public Health student, as well as important skills in novel investigational methods of determining bone strength. If awarded, this grant will support Dr. Fazeli's training in clinical research, with the ultimate goal of becoming an independent investigator with an expertise in combining neuroendocrinology and bone biology to better understand the pathophysiology of bone loss in disorders of under-nutrition.

描述（由申请人提供）：神经性厌食症（AN）影响美国0.5-1%的大学年龄女性，其特征是极端的自我诱导饥饿。在与AN相关的许多医学共病中，严重的骨丢失是最常见的，并且尽管体重恢复，但通常仍持续存在。这种骨丢失是显著的，因为患有AN的女性也具有增加的骨折风险;一项前瞻性研究表明，与年龄匹配的对照组相比，患有AN的女性的骨折风险增加了7倍。因此，预防与AN相关的严重骨丢失的治疗至关重要。目前尚无获批的治疗AN相关骨丢失的方法。在正常体重、性腺功能减退的妇女中预防骨丢失的疗法，如雌激素，不能改善AN妇女的骨密度。这可能是因为营养缺乏引起的骨丢失的发病机制与绝经后骨质疏松症不同。在AN中，骨形成显著减少。因此，刺激骨形成的试剂将是重要的潜在治疗。目前，特立帕肽（PTH）是FDA批准用于治疗骨质疏松症的唯一合成代谢药物。由于已知PTH对骨的影响是通过IGF-I介导的，并且在营养缺乏的状态下IGF-I水平较低，因此我们建议研究PTH对AN女性骨量的影响。我们将30名AN患者随机分为PTH组和安慰剂组，并前瞻性随访6个月。我们将在基线和6个月时测量骨矿物质密度、骨微结构参数和骨强度。我们还将在基线和研究期间每月测量骨形成和吸收的标志物、IGF-I和硬化素水平。Fazeli博士是哈佛医学院的医学讲师和马萨诸塞州总医院（MGH）的医学助理。她是在MGH神经内分泌单位的工作人员，并致力于她的大部分时间用于临床研究。她在研究AN激素异常方面的专业知识使她能够领导拟议的项目。她得到了MGH的大力支持，并可以充分利用神经内分泌科、临床研究中心和哈佛Catalyst CTSC的资源。她的共同导师安妮·克里班斯基博士和玛丽·布克森博士资金充足，并对法泽利博士的研究方向进行了投资。在获奖期间，Fazeli博士将在哈佛公共卫生学院获得生物统计学和研究设计方面的关键培训，她目前是该学院的公共卫生硕士生，以及确定骨强度的新研究方法的重要技能。Fazeli博士的临床研究培训，最终目标是成为一名独立的研究者，具有神经内分泌学和骨生物学相结合的专业知识，以更好地了解营养不良疾病中骨丢失的病理生理学。