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: 10190984
• 负责人: Pouneh Khadejeh Fazeli
• 金额: $ 32.37万
• 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/10190984
• 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; 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.

项目摘要/摘要 神经性厌食症在美国影响多达2％的女性，其特征是极端，自我诱发 饥饿。在与这种疾病相关的许多医疗合并症中，严重的骨质流失最多 尽管体重恢复了，但经常持续存在。重要的是，这种骨质流失与增加有关 骨折的风险；一项前瞻性研究表明，神经性厌食症的女性增加了7倍 与年龄匹配的对照相比，断裂的风险。因此，一种治疗以防止严重的骨质流失 与该疾病有关的 相关的骨质流失。我们最近表明，用teriparatide进行6个月的治疗会增加腰 神经性厌食症的女性，脊柱骨矿物质密度（BMD）比6％，但使用teriparatide仅是 批准了24个月，大多数患者患有这种疾病数十年。双膦酸盐，它 使用12个月后，将BMD提高3-4％，还具有长期使用的潜在有害影响（即 长时间使用的非典型股骨骨折）。因此，该病的最佳治疗方法将 不仅有效地增加了BMD，而且还可以长期使用。闭经和结果 性雌激素血症 - 神经性厌食症女性的特征性发现 - 这种疾病中骨骼质量的损失。这是由闭经持续时间直接的事实支持的 与神经性厌食症女性的BMD低相关。然而，尽管有这种关联，但多次研究 研究口服雌激素对神经性厌食症的妇女的影响尚未显示出好处。 最近，已显示雌激素可以增加神经性厌食症的青春期女孩的BMD，但 尚不清楚神经性厌食症女性的雌激素是否会改善雌激素的BMD。事先治疗 研究表明，神经性厌食症的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响应一年 在双膦酸盐治疗中，用双膦酸盐治疗一年的青少年没有显着 与接受安慰剂治疗的人相比，BMD的增加。因此，可能有效的治疗方法 人口可能不会有效。我们的初步数据显示脊柱BMD增加了2.1％ 在用6个月的经皮雌激素置换治疗的神经性厌食症的女性中 减少骨髓脂肪组织，这是骨骼质量的潜在决定因素。因此，我们建议执行 随机，双盲安慰剂对照研究，以研究透皮雌激素的影响 成年女性的骨骼质量，骨微体系结构和骨髓脂肪组织的替代厌食症 神经。通过研究骨骼质量，骨转换标记和骨髓变化之间的关联 脂肪组织响应透皮雌激素，我们也希望对 慢性营养不良状态的骨质流失的病理生理学。