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

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，其特征是极度的自我诱导饥饿。在许多与AN相关的医学合并症中，严重的骨丢失是最常见的，而且在体重恢复的情况下通常会持续存在。这种骨丢失是显著的，因为患有AN的女性也有更高的骨折风险；一项前瞻性研究表明，与年龄匹配的对照组相比，患有AN的女性发生骨折的风险增加7倍。因此，预防与AN相关的严重骨丢失的治疗是至关重要的。目前还没有被批准的治疗AN相关性骨丢失的方法。在正常体重、性腺功能低下的女性中，防止骨丢失的治疗方法，如雌激素，并不能改善患有AN的女性的骨密度。这可能是因为营养缺乏导致骨丢失的发病机制与绝经后骨质疏松症不同。在骨质疏松症中，骨形成显著减少。因此，一种刺激骨形成的药物将是一种重要的潜在治疗方法。目前，Teriparatide(PTH)是FDA批准的唯一用于治疗骨质疏松症的合成代谢药物。由于甲状旁腺激素对骨骼的影响是通过IGF-I介导的，而且在营养缺乏的情况下，IGF-I水平很低，我们建议研究甲状旁腺素对AN妇女骨量的影响。我们将随机选择30名接受甲状旁腺素或安慰剂治疗的女性，并前瞻性地跟踪观察6个月。在基线和6个月时测量骨密度、骨微结构参数和骨强度。在研究过程中，我们还将在基线和每月测量骨形成和骨吸收的标记物、IGF-I和硬化素水平。法泽利博士是哈佛医学院的医学讲师和马萨诸塞州综合医院的医学助理。她是麻省理工学院神经内分泌科的工作人员，大部分时间都致力于临床研究。她在研究荷尔蒙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的良好支持，并拥有完全访问神经内分泌科、临床研究中心和哈佛大学催化剂CTSC资源的权限。她的联合导师Anne Klibanski博士和Mary Bouxsein博士资金充足，并在Fazeli博士的研究方向上进行了投资。在获奖期间，Fazeli博士将在哈佛公共卫生学院接受生物统计学和研究设计方面的关键培训，她目前是该学院公共卫生硕士学生，并将获得确定骨骼强度的新研究方法方面的重要技能。如果获奖，这笔赠款将支持Fazeli博士在临床研究方面的培训，最终目标是成为一名独立研究员，拥有将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。

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.