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: 8662767
• 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/8662767
• 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）影响美国的0.5-1％的大学妇女，其特征是极端，自我诱发的饥饿。在与严重骨质流失相关的许多医疗合并症中，最常见的是，尽管体重恢复了。这种骨质流失很大，因为患有骨折风险的女性也会增加。一项前瞻性研究表明，与年龄匹配的对照相比，患有骨折风险的女性增加了7倍。因此，预防与AN相关的严重骨质流失的治疗是至关重要的。目前尚无批准与AN相关骨质流失的治疗方法。预防正常体重骨质损失的疗法，例如雌激素，不能改善AN女性的骨矿物质密度。这可能是因为由于营养剥夺引起的骨质流失的发病机理与绝经后骨质疏松症的发病机理不同。在AN中，骨形成急剧下降。因此，刺激骨形成的药物将是重要的潜在治疗方法。目前，Teriparatide（PTH）是FDA批准骨质疏松症的唯一合成代谢剂。由于已知PTH对骨骼的影响是通过IGF-I介导的，并且在营养缺乏状态下IGF-I水平较低，因此我们建议研究PTH对AN的女性骨骼量的影响。我们将随机将三十名女性与PTH或安慰剂进行治疗，并前瞻性地关注她们6个月。我们将测量骨矿物质密度，骨微结构的参数以及基线和6个月时的骨强度。在研究过程中，我们还将测量基线和每月的骨形成和吸收，IGF-I和硬化素水平的标记。 Fazeli博士是哈佛医学院医学教练，也是马萨诸塞州综合医院（MGH）的医学助理。她是MGH神经内分泌部门的工作人员，并将大部分时间用于临床研究。她在研究激素异常方面的专业知识使她领导了拟议项目。她得到了MGH的良好支持，并可以完全访问神经内分泌部门，临床研究中心和哈佛催化剂CTSC资源。她的联合官员，博士。安妮·克里班斯基（Anne Klibanski）和玛丽·布克森（Mary Bouxsein）获得了充分的资金，并投入了Fazeli博士的研究方向。在奖励期间，法兹利博士将在哈佛公共卫生学院获得生物统计学和研究设计的重要教学，她目前是公共卫生学生的硕士，以及确定骨骼力量的新型研究方法的重要技能。如果获得奖励，该赠款将支持Fazeli博士在临床研究方面的培训，最终的目的是成为具有结合神经内分泌学和骨骼生物学的专业知识的独立研究者，以更好地了解不良疾病疾病骨质损失的病理生理学。