Kearbey Jeffrey D, Gao Wenqing, Narayanan Ramesh, Fisher Scott J, Wu Di, Miller Duane D, Dalton James T
College of Pharmacy, Division of Pharmaceutics, The Ohio State University, Columbus, Ohio 43210, USA.
Pharm Res. 2007 Feb;24(2):328-35. doi: 10.1007/s11095-006-9152-9. Epub 2006 Oct 25.
This study was conducted to examine the bone and body composition effects of S-4, an aryl-propionamide derived Selective Androgen Receptor Modulator (SARM) in an ovariectomy induced model of accelerated bone loss.
One hundred twenty female Sprague-Dawley rats aged to twenty-three weeks were randomly assigned to twelve treatment groups. Drug treatment was initiated immediately following ovariectomy and continued for one hundred twenty days. Whole body bone mineral density (BMD), body composition, and lumbar vertebrae BMD were measured by dual energy x-ray absorptiometry. More stringent regional pQCT and biomechanical strength testing was performed on excised femurs.
We found that S-4 treatment maintained whole body and trabecular BMD, cortical content, and increased bone strength while decreasing body fat in these animals.
The data presented herein show the protective skeletal effects of S-4. Our previous reports have shown the tissue selectivity and muscle anabolic activity of S-4. Together these data suggest that S-4 could reduce the incidence of fracture via two different mechanisms (i.e., via direct effects in bone and reducing the incidence of falls through increased muscle strength). This approach to fracture reduction would be advantageous over current therapies in these patients which are primarily antiresorptive in nature.
本研究旨在探讨S-4(一种芳基丙酰胺衍生的选择性雄激素受体调节剂(SARM))在卵巢切除诱导的加速骨质流失模型中对骨骼和身体成分的影响。
将120只23周龄的雌性Sprague-Dawley大鼠随机分为12个治疗组。卵巢切除后立即开始药物治疗,并持续120天。采用双能X线吸收法测量全身骨矿物质密度(BMD)、身体成分和腰椎BMD。对切除的股骨进行更严格的局部外周定量CT和生物力学强度测试。
我们发现S-4治疗可维持这些动物的全身和小梁骨密度、皮质含量,并增加骨强度,同时减少体脂。
本文提供的数据显示了S-4对骨骼的保护作用。我们之前的报告显示了S-4的组织选择性和肌肉合成代谢活性。这些数据共同表明,S-4可以通过两种不同的机制降低骨折发生率(即通过对骨骼的直接作用和通过增加肌肉力量降低跌倒发生率)。这种降低骨折发生率的方法相对于目前主要为抗吸收性质的这些患者的治疗方法具有优势。