Effect of a ghrelin receptor agonist on muscle and bone

项目总结 同时患有骨量减少和骨质疏松症(骨质疏松症)的成年人跌倒和骨折的风险比 骨质疏松症或骨质疏松症患者。可以使用药物来降低骨折风险，但目前运动是 对抗肌肉流失的唯一有效策略。不幸的是，大多数开始自我生活的成年人 受监测的锻炼计划在6个月后退出，需要其他选择。Ghrelin受体激动剂 一直在开发用于治疗癌症恶病质患者的厌食症和体重减轻。激动剂 阿那莫瑞林显著增加了这些患者的体重和瘦组织质量。Anamorelin模拟 Ghrelin激素，它不仅增加磷灰石，而且作用于脑下垂体以促进搏动性生长 激素(GH)分泌。脉冲式生长激素刺激合成代谢的胰岛素样生长因子1的产生 对肌肉和骨骼都是如此。生长激素水平随着年龄的增长而下降，这被认为是与年龄相关的肌肉的形成原因 以及成年人的骨质流失。我们的中心假设是Anamorelin会增加肌肉质量，改善 骨质疏松症患者的肌肉功能和骨形成增加。为了检验这一假设，我们将 在40名骨质疏松症患者中进行随机、双盲、双臂、平行分组干预试验 50岁及以上的绝经后妇女。参与者将被随机服用阿那莫瑞林(每天100毫克)或 服用安慰剂，治疗12个月。主要终点是阑尾瘦组织块增加 用双能x射线吸收计量仪测量。次要终点是：增加肌肉力量 (腿部等长力量)和功能(6分钟步行和改良的短体能电池)， 骨形成生物标志物氨基末端前肽(P1NP)增加，总瘦肉量增加 组织块。拟议中的治疗方法提供了合成代谢的刺激，以建立肌肉和骨骼。 阿那莫瑞林还没有在患有骨质疏松症的成年人身上进行测试。我们建议在#年评估这种治疗方法。 最需要治疗，也最有可能受益的成骨性成骨细胞。数据 从这项初步研究中获得的信息对于确定可行性和指导最终试验的设计至关重要 评估该Ghrelin受体激动剂作为缓解骨量减少和骨量减少的双重危险的潜在治疗方法。 石棺减少症。

PROJECT SUMMARY Adults with both osteopenia and sarcopenia (osteosarcopenia) have greater risk of falls and fractures than those with osteopenia or sarcopenia alone. Drugs are available to reduce fracture risk but currently exercise is the only effective strategy to combat muscle loss. Unfortunately, the majority of adults who start a self- monitored exercise program drop out after 6 months and other options are needed. Ghrelin receptor agonists have been under development to treat anorexia and weight loss in patients with cancer cachexia. The agonist anamorelin has significantly increased weight and lean tissue mass in these patients. Anamorelin mimics the hormone ghrelin which not only increases apatite, but also acts on the pituitary to increase pulsatile growth hormone (GH) secretion. Pulsatile GH stimulates the production of insulin-like growth factor 1 which is anabolic to both muscle and bone. GH levels decline with age and this is thought to contribute to the age-related muscle and bone losses in adults. Our central hypothesis is that anamorelin will increase muscle mass, improve muscle function, and increase bone formation in adults with osteosarcopenia. To test this hypothesis, we will conduct a randomized, double-blind, 2-armed, parallel-group intervention trial in 40 osteosarcopenic men and postmenopausal women age 50 and older. Participants will be randomized to anamorelin (100 mg per day) or placebo and treated for 12 months. The primary endpoint is increase in appendicular lean tissue mass measured by dual-energy x-ray absorptiometry. Secondary endpoints are: increases in muscle strength (isometric leg strength) and function (6-minute walk and modified short physical performance battery), an increase in the bone formation biomarker, amino-terminal propeptide (P1NP), and an increase in total lean tissue mass. The proposed treatment supplies the anabolic stimulus to build both muscle and bone. Anamorelin has not been tested in adults with osteosarcopenia. We propose to evaluate this treatment in osteosarcopenic adults who are most in need of treatment and who are also most likely to benefit. Data obtained from this pilot study are critical to determine the feasibility and guide the design of a definitive trial to evaluate this ghrelin receptor agonist as potential therapy to mitigate the dual hazards of osteopenia and sarcopenia.