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

项目摘要/摘要 神经性厌食症在美国影响多达2%的女性，其特征是极端的、自我诱导的 饿死了。在许多与这种疾病相关的医学合并症中，严重的骨丢失是最常见的 这很常见，尽管体重有所恢复，但往往会持续存在。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的风险增加了7倍 与年龄匹配的对照组相比，骨折的风险。因此，一种预防严重骨丢失的治疗方法 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- 相关的骨丢失。我们最近的研究表明，6个月的特瑞帕泰治疗可以增加腰椎。 神经性厌食症妇女的脊柱骨密度(BMD)降低6%，但仅使用特瑞帕泰 批准了24个月，大多数患者与这种疾病生活了几十年。双膦酸盐，它 使用12个月后骨密度增加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，治疗骨质疏松症的最佳治疗方法是 不仅能有效增加BMD，还能长期使用。闭经及由此引起的 低雌激素血症--神经性厌食症女性的特征表现--是导致 骨质疏松症这种疾病中的骨量损失。闭经时间的长短直接影响到 与神经性厌食症妇女的低骨密度有关。然而，尽管存在这种联系，多项研究 研究口服雌激素对患有神经性厌食症的女性的影响并没有显示出好处。 最近，经皮雌激素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 经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。前期治疗 研究表明，患有神经性厌食症的青少年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在一年内增加了3%-4% 在双磷酸盐治疗中，青少年使用双磷酸盐治疗一年没有显著的 与服用安慰剂的人相比，骨密度增加。因此，一种可能有效的治疗方法 人口在另一种情况下可能并不有效。我们的初步数据显示脊柱骨密度增加了2.1% 对患有神经性厌食症的妇女进行6个月的经皮雌激素替代联合 骨髓脂肪组织减少，这是骨量的一个潜在决定因素。因此，我们建议执行一项 雌激素透皮吸收的随机、双盲、安慰剂对照研究 成年女性厌食症患者的骨量、骨微结构和骨髓脂肪组织置换 神经质。通过研究骨量、骨转换标志物和骨髓变化之间的关系 脂肪组织对经皮雌激素的反应，我们也希望对其有更大的了解 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.