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本文引用的文献

1
Chemistry and structural biology of androgen receptor.雄激素受体的化学与结构生物学
Chem Rev. 2005 Sep;105(9):3352-70. doi: 10.1021/cr020456u.
2
Selective androgen receptor modulator treatment improves muscle strength and body composition and prevents bone loss in orchidectomized rats.选择性雄激素受体调节剂治疗可改善去势大鼠的肌肉力量和身体成分,并预防骨质流失。
Endocrinology. 2005 Nov;146(11):4887-97. doi: 10.1210/en.2005-0572. Epub 2005 Aug 11.
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Differential skeletal responses of hindlimb unloaded rats on a vitamin D-deficient diet to 1,25-dihydroxyvitamin D3 and its analog, seocalcitol (EB1089).
Bone. 2004 Jul;35(1):134-43. doi: 10.1016/j.bone.2004.02.014.
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Pharmacokinetics of S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro- 3-trifluoromethyl-phenyl)-propionamide in rats, a non-steroidal selective androgen receptor modulator.非甾体选择性雄激素受体调节剂S-3-(4-乙酰氨基苯氧基)-2-羟基-2-甲基-N-(4-硝基-3-三氟甲基苯基)丙酰胺在大鼠体内的药代动力学
Xenobiotica. 2004 Mar;34(3):273-80. doi: 10.1080/0049825041008962.
5
Bone anabolic effects of S-40503, a novel nonsteroidal selective androgen receptor modulator (SARM), in rat models of osteoporosis.新型非甾体选择性雄激素受体调节剂(SARM)S-40503在骨质疏松大鼠模型中的骨合成代谢作用
Biol Pharm Bull. 2003 Nov;26(11):1563-9. doi: 10.1248/bpb.26.1563.
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A prospective evaluation of bone mineral density measurement in females who have fallen.对跌倒女性进行骨密度测量的前瞻性评估。
Age Ageing. 2003 Sep;32(5):497-502. doi: 10.1093/ageing/afg062.
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Pharmacodynamics of selective androgen receptor modulators.选择性雄激素受体调节剂的药效学
J Pharmacol Exp Ther. 2003 Mar;304(3):1334-40. doi: 10.1124/jpet.102.040840.
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Key structural features of nonsteroidal ligands for binding and activation of the androgen receptor.用于雄激素受体结合和激活的非甾体配体的关键结构特征。
Mol Pharmacol. 2003 Jan;63(1):211-23. doi: 10.1124/mol.63.1.211.
9
Osteoblast differentiation influences androgen and estrogen receptor-alpha and -beta expression.成骨细胞分化影响雄激素受体和雌激素受体α及β的表达。
J Endocrinol. 2002 Dec;175(3):683-94. doi: 10.1677/joe.0.1750683.
10
Sex steroid metabolism in the tibial growth plate of the rat.大鼠胫骨生长板中的性类固醇代谢
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选择性雄激素受体调节剂(SARM)治疗可预防去卵巢大鼠的骨质流失并减少体脂。

Selective Androgen Receptor Modulator (SARM) treatment prevents bone loss and reduces body fat in ovariectomized rats.

作者信息

Kearbey Jeffrey D, Gao Wenqing, Narayanan Ramesh, Fisher Scott J, Wu Di, Miller Duane D, Dalton James T

机构信息

College of Pharmacy, Division of Pharmaceutics, The Ohio State University, Columbus, Ohio 43210, USA.

出版信息

Pharm Res. 2007 Feb;24(2):328-35. doi: 10.1007/s11095-006-9152-9. Epub 2006 Oct 25.

DOI:10.1007/s11095-006-9152-9
PMID:17063395
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2039878/
Abstract

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

目的

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。

方法

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。

结果

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。

结论

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。