IGF-1 and Bone Loss in Women with Anorexia Nervosa

神经性厌食症女性的 IGF-1 和骨质流失

• 批准号: 8063348
• 负责人: ANNE KLIBANSKI
• 金额: $ 9.21万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-14 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8063348
• 关键词: Address; Affect; Age; Anabolic Agents; Anorexia Nervosa; Area; Bone Density; Bone Resorption; Combined Modality Therapy; Complication; Coupled; Data; Disease; Effectiveness; Estrogens; Fatty acid glycerol esters; Fracture; Insulin-Like Growth Factor I; Investigation; Malnutrition; Muscle; Oral Contraceptives; Osteogenesis; Osteopenia; Osteoporosis; Pharmaceutical Preparations; Physiological; Placebos; Population; Postmenopause; Prevalence; Recombinant IGF-I; Regimen; Risedronate; Risk; Serum; Site; Skeletal Muscle; Somatotropin; Testing; Therapeutic; Therapeutic Intervention; Thick; Thigh structure; Vertebral column; Woman; X-Ray Computed Tomography; bisphosphonate; bone; bone loss; bone mass; college; cone-beam computed tomography; design; digital; effective therapy; hormone resistance; improved; medical complication; muscle form; prevent; skeletal; ultra high resolution

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.

项目概要 严重骨质减少是神经性厌食症 (AN) 的常见并发症，影响超过一半的患者 所有患有这种疾病的女性。骨质流失经常发生，而且往往是永久性的。 一个或多个骨骼部位的骨矿物质密度 (BMD) 降低至少 1.0 SD 超过 90% 的受试者，超过 1/3 的受试者至少有 2.5 个标准差。而且，这种减少 与 30% 的骨折发生率相关。尽管 AN 影响 0.5-1.0% 的大学- 老年女性，尚未开发出成功的治疗干预措施来预防骨质流失 或增加年轻人群的骨量。我们的初步数据显示严重的骨质疏松 结构异常，包括小梁厚度显着减少，小梁 数量和骨量以及小梁分离的增加。 AN 中的骨丢失是 其特点是骨形成减少，骨吸收增加。厌食症 nervosa 会导致生长激素 (GH) 抵抗并导致严重的胰岛素样生长 营养不良导致因子 1 (IGF-1) 缺乏。这是获得性 IGF-1 缺乏症， 内源性骨营养因子是骨形成减少的重要决定因素 这个人口。众所周知，IGF-1 对骨骼具有合成代谢作用，我们已经证明 通过施用重组药物，AN 女性的骨形成和 BMD 增加 IGF-1（rhIGF-1）。然而，尽管骨形成增加，骨吸收仍然很高， 需要一种有效减少营养不良状态下吸收的治疗方法。 双磷酸盐已被证实可以减少骨吸收并改善骨密度 严重骨质疏松的绝经后妇女，我们的初步数据表明， 患有 AN 的女性 BMD 增加。使用合成代谢和抗再吸收疗法的最新数据 已经表明序贯治疗可能会导致 BMD 比同时治疗有更大的改善 给予联合治疗。没有数据调查此类治疗策略 在这个人群中，没有既定的治疗方法。我们将检验以下假设： 实施合成代谢疗法 rhIGF-1 的策略，为期六个月，然后进行 双膦酸盐、利塞膦酸盐，六个月会增加骨量并改善 神经性厌食症女性的微结构。