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.

项目摘要 严重骨质减少是神经性厌食症（AN）的常见并发症， 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 在超过90%的受试者中，超过1/3的受试者中至少2.5 SD。此外，这种减少 与30%的骨折患病率有关虽然AN影响从0.5-1.0%的大学- 对于年龄较大的女性，还没有成功的治疗干预措施来预防骨质流失。 或者增加年轻人的骨量。我们的初步数据显示 结构异常，包括骨小梁厚度明显减少， 数量和骨体积以及骨小梁分离增加。AN中的骨丢失是 其特征在于减少的骨形成伴随增加的骨吸收。厌食 神经型糖尿病导致生长激素（GH）抵抗和严重的胰岛素样生长 因子1（IGF-1）缺乏症，由于营养不良。这种IGF-1的获得性缺乏， 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。已知IGF-1对骨骼具有合成代谢作用，我们已经证明 给予重组蛋白后AN女性的骨形成和骨密度增加 IGF-1（rhIGF-1）。然而，尽管骨形成增加，骨吸收仍然很高， 需要一种在营养不良状态下有效减少再吸收的疗法。 双膦酸盐已被公认可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， 增加女性的骨密度。使用合成代谢和抗吸收疗法的最新数据 表明序贯治疗可能会导致骨密度增加， 给予联合治疗。目前尚无研究此类治疗策略的数据 在这个人群中，没有既定的治疗方法。我们将检验这个假设， 一种策略，给予合成代谢疗法，rhIGF-1，为期六个月，随后是 双膦酸盐，利塞膦酸盐，六个月将增加骨量，改善 神经性厌食症妇女的微结构。