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.

项目总结