IGF-1 and Bone Loss in Women with Anorexia Nervosa

项目摘要 严重的骨量减少是神经性厌食症(AN)的一种普遍并发症，影响到超过一半的 所有患有这种疾病的女性。骨量丢失经常发生，而且往往是永久性的。 一个或多个骨骼部位的骨密度(BMD)降低至少1.0SD 超过90%的受试者和超过1/3的受试者至少2.5SD。此外，这一削减 与30%的骨折患病率有关。尽管影响了0.5%-1.0%的大学毕业生- 对于年龄较大的妇女，还没有成功的治疗干预措施来预防骨丢失 或者增加这一年轻人群的骨量。我们的初步数据显示严重的骨骼 结构异常，包括小梁厚度显著减少，小梁 数量和骨体积增加，骨小梁间距增加。IS中的骨丢失 以骨形成减少和骨吸收增加为特征的。厌食症 神经性疾病导致生长激素(GH)抵抗和严重的胰岛素样生长 1因子(IGF-1)缺乏，因营养不良。这种IGF-1的获得性缺陷，以及 内源性骨营养因子是骨形成减少的重要决定因素 这群人。IGF-1已知对骨骼有合成代谢作用，我们已经证明 服用重组蛋白的AN妇女骨形成和骨密度增加 胰岛素样生长因子-1(rhIGF-1)。然而，尽管骨形成增加，骨吸收仍然很高， 在营养不良的情况下，需要一种有效减少吸收的治疗方法。 双膦酸盐具有减少骨吸收和改善骨密度的作用。 严重的骨质疏松症绝经后妇女，我们的初步数据表明 患有骨质疏松症的女性的骨密度增加。使用合成代谢疗法和抗吸收疗法的最新数据 已经提出序贯疗法可能导致更大的骨密度增加，同时 接受联合治疗。目前还没有研究这种治疗策略的数据 在这一人群中，他们没有既定的治疗方法。我们将检验这一假设 一种策略，实施合成代谢疗法，重组人IGF-1，为期六个月，然后 双磷酸盐，利塞膦酸盐，服用6个月将增加骨量并改善 神经性厌食症妇女的微建筑。

Project Summary Severe osteopenia is a prevalent complication of anorexia nervosa (AN), affecting over half of all women with this disease. Loss of bone mass occurs frequently and is often permanent. Reduction of bone mineral density (BMD) by at least 1.0 SD at one or more skeletal sites occurs in over 90% of subjects and by at least 2.5 SD in over 1/3 of subjects. Moreover, this reduction is associated with a 30% prevalence of fractures. Although AN affects from 0.5-1.0% of college- age women, no successful therapeutic interventions have been developed to prevent bone loss or increase bone mass in this young population. Our preliminary data demonstrate severe bone structural abnormalities as well, including markedly reduced trabecular thickness, trabecular number and bone volume and increased trabecular separation. Bone loss in AN is characterized by reduced bone formation coupled with increased bone resorption. Anorexia nervosa results in growth hormone (GH) resistance and resultant severe insulin-like growth factor 1 (IGF-1) deficiency due to undernutrition. This acquired deficiency of IGF-1, an endogenous bone trophic factor, is an important determinant of decreased bone formation in this population. IGF-1 is known to have anabolic actions on bone, and we have demonstrated increases in bone formation and BMD in women with AN with administration of recombinant IGF-1 (rhIGF-1). However, despite increasing bone formation, bone resorption remains high, and a therapy to effectively decrease resorption in the state of undernutrition is needed. Bisphosphonates are well established to decrease bone resorption and improve BMD in severely osteopenic postmenopausal women, and our preliminary data demonstrate significant increases in BMD in women with AN. Recent data using anabolic and anti-resorptive therapies have suggested that sequential therapy may result in greater gains in BMD that concurrently administered combination therapy. There are no data investigating such therapeutic strategies in this population, in whom there are no established therapies. We will test the hypothesis that a strategy to administer an anabolic therapy, rhIGF-1, for six months followed by a bisphosphonate, risedronate, for six months will increase bone mass and improve microarchitecture in women with anorexia nervosa.