Transdermal estrogen for the treatment of bone loss in women with anorexia nervosa

透皮雌激素治疗神经性厌食症女性骨质流失

• 批准号: 10443738
• 负责人: Pouneh Khadejeh Fazeli
• 金额: $ 33.75万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10443738
• 关键词: Adipose tissue; Adolescent; Adult; Affect; Age; Amenorrhea; Anorexia Nervosa; Area; Body Weight; Body Weight decreased; Bone Density; Bone Marrow; Bone Resorption; Cell Count; Characteristics; Chronic; Complication; Coupled; Data; Disease; Dissection; Double-Blind Method; Elements; Estrogen Replacements; Estrogen Therapy; Estrogens; Fatty acid glycerol esters; Female Adolescents; Femoral Fractures; Forteo; Fracture; Functional disorder; Hematopoietic stem cells; Investigation; Magnetic Resonance Spectroscopy; Malnutrition; Marrow; Measures; Medical; Mental disorders; Metabolism; Minerals; Morbidity - disease rate; Oral; Osteogenesis; Osteoporosis; Patients; Peripheral; Physiological; Placebo Control; Placebos; Population; Population Control; Prevalence; Prospective Studies; Randomized; Recovery; Red Blood Cell Count; Resolution; Role; Starvation; Testing; Therapeutic; Time; Underweight; Vertebral column; Visceral; Weight; Woman; bisphosphonate; bone; bone loss; bone mass; bone strength; bone turnover; comorbidity; fracture risk; hematopoietic stem cell niche; improved; insight; medical complication; mortality; optimal treatments; placebo controlled study; prevent; randomized controlled study; randomized placebo controlled study; response; spine bone structure; subcutaneous; transdermal estrogen; treatment response; young woman

Project Summary/Abstract Anorexia Nervosa affects up to 2% of women in the US and is characterized by extreme, self-induced starvation. Of the many medical co-morbidities associated with this disorder, severe bone loss is the most common and often persists despite weight recovery. Importantly, this bone loss is associated with an increased risk of fracture; a prospective study demonstrated that women with anorexia nervosa have a 7-fold increased risk of fracture compared to age-matched controls. Therefore, a treatment to prevent the severe bone loss associated with this disease is critical, but there are currently no approved treatments for anorexia nervosa- associated bone loss. We have recently shown that 6 months of treatment with teriparatide increases lumbar spine bone mineral density (BMD) by 6% in women with anorexia nervosa but use of teriparatide is only approved for 24 months and the majority of patients live with this disease for decades. Bisphosphonates, which increase BMD by 3-4% after 12 months of use, also have potential harmful effects with long-term use (ie atypical femoral fractures with prolonged use). Therefore, an optimal treatment for bone loss in this disease will not only effectively increase BMD, but will also be available for long-term use. Amenorrhea and resultant hypoestrogenemia -- characteristic findings in women with anorexia nervosa -- are significant contributors to the loss of bone mass in this disease. This is supported by the fact that duration of amenorrhea is directly associated with low BMD in women with anorexia nervosa. Yet, despite this association, multiple studies investigating the effects of oral estrogen in women with anorexia nervosa have not demonstrated a benefit. Recently, transdermal estrogen has been shown to increase BMD in adolescent girls with anorexia nervosa but whether transdermal estrogen will improve BMD in women with anorexia nervosa is not known. Prior treatment studies have demonstrated distinctly different responses to treatments in adolescents with anorexia nervosa as compared to adults. For example, although BMD in adult women increases by 3-4% in response to one-year of bisphosphonate treatment, adolescents treated with bisphosphonates for one-year do not have a significant increase in BMD compared to those treated with placebo. Therefore, treatments that may be effective in one population may not be effective in the other. Our preliminary data demonstrate a 2.1% increase in spine BMD in women with anorexia nervosa treated with 6 months of transdermal estrogen replacement coupled with a decrease in marrow adipose tissue, a potential determinant of bone mass. Therefore, we propose to perform a randomized, double-blind placebo-controlled study to investigate the effects of transdermal estrogen replacement on bone mass, bone microarchitecture and marrow adipose tissue in adult women with anorexia nervosa. By investigating associations between changes in bone mass, bone turnover markers and marrow adipose tissue in response to transdermal estrogen, we also hope to gain a greater understanding of the pathophysiology of bone loss in states of chronic undernutrition.

项目概要/摘要 神经性厌食症影响着美国高达 2% 的女性，其特点是极端的、自我诱发的 饥饿。在与这种疾病相关的许多医学并发症中，严重的骨质流失是最严重的 尽管体重恢复，但这种情况很常见并且经常持续存在。重要的是，这种骨质流失与骨量增加有关。 骨折的风险；一项前瞻性研究表明，患有神经性厌食症的女性的食欲增加了 7 倍。 与年龄匹配的对照相比，骨折的风险。因此，预防严重骨质流失的治疗 与这种疾病相关的疾病是至关重要的，但目前还没有批准的治疗神经性厌食症的方法 相关的骨质流失。我们最近表明，特立帕肽治疗 6 个月可增强腰椎功能 神经性厌食症女性的脊柱骨密度 (BMD) 降低 6%，但仅使用特立帕肽 批准有效期为 24 个月，大多数患者患有这种疾病数十年。双膦酸盐，其中 使用12个月后BMD增加3-4%，长期使用也有潜在的有害影响（即 长期使用导致非典型股骨骨折）。因此，针对这种疾病的骨质流失的最佳治疗方法是 不仅可以有效增加BMD，而且可以长期使用。闭经及其后果 低雌激素血症——神经性厌食症女性的典型表现——是导致 这种疾病导致骨质流失。闭经持续时间直接影响这一事实也支持了这一点。 与神经性厌食症女性的低骨密度有关。然而，尽管存在这种关联，多项研究 研究口服雌激素对神经性厌食症女性的影响尚未证明有益处。 最近，经皮雌激素已被证明可以增加患有神经性厌食症的青春期女孩的骨密度，但 透皮雌激素是否会改善神经性厌食症女性的骨密度尚不清楚。既往治疗 研究表明，神经性厌食症青少年对治疗的反应截然不同 与成人相比。例如，尽管成年女性的 BMD 在一年内增加了 3-4% 就双膦酸盐治疗而言，接受双膦酸盐治疗一年的青少年并没有显着 与安慰剂治疗组相比，BMD 有所增加。因此，可能对某一方面有效的治疗 人口可能在其他方面没有效果。我们的初步数据显示脊柱 BMD 增加了 2.1% 患有神经性厌食症的女性接受 6 个月的透皮雌激素替代疗法并结合 骨髓脂肪组织减少，这是骨量的潜在决定因素。因此，我们建议执行 随机、双盲安慰剂对照研究，探讨透皮雌激素的作用 厌食症成年女性的骨量、骨微结构和骨髓脂肪组织的替代 紧张。通过研究骨量变化、骨转换标志物和骨髓之间的关联 脂肪组织对透皮雌激素的反应，我们也希望能更深入地了解 慢性营养不良状态下骨质流失的病理生理学。