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

项目总结/摘要 神经性厌食症影响了美国2%的女性，其特点是极端的，自我诱导的 饥饿在与这种疾病相关的许多医学共病中，严重的骨丢失是最常见的。 常见的，并经常持续，尽管体重恢复。重要的是，这种骨丢失与增加的 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， 与年龄匹配的对照组相比，骨折风险。因此，治疗，以防止严重的骨质流失， 与这种疾病相关的是至关重要的，但目前还没有批准的治疗神经性厌食症- 相关的骨质流失。我们最近的研究表明，6个月的teriparbazole治疗可以增加腰椎 脊柱骨密度（BMD）下降6%，但使用特立哌酮仅 批准为24个月，大多数患者患有这种疾病数十年。双膦酸盐， 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 长期使用的非典型股骨骨折）。因此，对于这种疾病的骨丢失的最佳治疗将 不仅能有效增加骨密度，而且可以长期使用。闭经及其后果 低雌激素血症--神经性厌食症妇女的特征性发现--是导致 这种疾病中骨质的流失。这一点得到以下事实的支持，即闭经的持续时间直接影响 与神经性厌食症女性的低BMD相关。然而，尽管存在这种关联， 研究口服雌激素对神经性厌食症妇女的作用没有显示出益处。 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BMD， 经皮雌激素是否会改善神经性厌食症妇女的BMD尚不清楚。既往治疗 研究表明，青少年神经性厌食症患者对治疗的反应明显不同， 与成年人相比。例如，尽管成年女性的BMD在一年的治疗后增加了3-4%， 在双膦酸盐治疗中，青少年接受双膦酸盐治疗一年后， 与安慰剂治疗组相比，BMD增加。因此，可能对一种疾病有效的治疗方法 在另一种情况下，人口可能不会有效。我们的初步数据表明，脊柱骨密度增加2.1%， 在接受6个月经皮雌激素替代治疗的神经性厌食症妇女中， 骨髓脂肪组织减少，这是骨量的潜在决定因素。因此，我们建议执行一项 一项随机、双盲、安慰剂对照研究，旨在研究经皮雌激素的作用 厌食症成年女性骨量、骨微结构和骨髓脂肪组织的替代 神经。通过研究骨量变化、骨转换标志物和骨髓 脂肪组织对经皮雌激素的反应，我们也希望能更好地了解 慢性营养不良状态下骨丢失的病理生理学。

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.