Evaluation of ostarine as a selective androgen receptor modulator in a rat model of postmenopausal osteoporosis
Evaluation of ostarine as a selective androgen receptor modulator in a rat model of postmenopausal osteoporosis
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DOI：
10.1007/s00774-018-0929-9
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发表时间：
2019-03-01
影响因子：
3.3
通讯作者：
Sehmisch, S.
中科院分区：
文献类型：
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作者：
Hoffmann, D. B.;Komrakova, M.;Sehmisch, S.
选择性雄激素受体调节剂（SARMs）对雄性哺乳动物的肌肉萎缩、一般身体机能和骨骼特性有有益的影响。然而，关于SARMs对绝经后骨质疏松性骨的影响的数据很少。我们在大鼠骨质疏松模型中评估了SARM药物ostarine对绝经后骨质疏松性骨的影响。对56只3月龄雌性Sprague-Dawley大鼠中的46只进行卵巢切除术。卵巢切除术后8周，每天口服ostarine，剂量为0.04（低，OVX+Ost），持续5周。0.04), 0.4(中间，OVX+Ost。0.4)和4mg/kg(高，OVX+Ost。4)体重。另一组卵巢切除组不给予卵磷脂。切除腰椎和股骨进行生物力学、基因表达、灰化和计算机断层扫描分析。低剂量无影响。中等剂量和高剂量的总体效果相当。改善主要体现在骨矿物质密度和骨体积密度等结构特性上。然而，对股骨的影响优于对椎骨的影响。Ostarine治疗5周后，生物力学性能无明显改善。治疗后NF-B配体受体激活剂mRNA表达降低，子宫重量增加。中剂量组和高剂量组血清磷水平升高。短时间内用ostarine治疗骨质疏松症，可改善几种骨显微结构指标。虽然我们没有观察到生物力学的变化，但可以想象，更长时间的治疗也可能改善生物力学性能。需要进一步的研究来确定ostarine在骨质疏松症中的长期作用和副作用。
Selective androgen receptor modulators (SARMs) have shown beneficial effects on muscle wasting, general physical function and bone properties in male mammals. However, data on the effects of SARMs in postmenopausal osteoporotic bone are scarce. We evaluated the effects of the SARM drug ostarine on postmenopausal osteoporotic bone in a rat osteoporosis model. Ovariectomy was performed on 46 of 56 3-month-old female Sprague-Dawley rats. Eight weeks after ovariectomy, ostarine was orally administered daily for 5weeks in dosages of 0.04 (low, OVX+Ost. 0.04), 0.4 (intermediate, OVX+Ost. 0.4), and 4mg/kg (high, OVX+Ost. 4) body weight. Another ovariectomized group received no ostarine. Lumbar vertebrae and femora were removed for biomechanical, gene expression, ashing, and computer tomography analyses. Low dose showed no effects. The effects of intermediate and high doses were comparable overall. Improvements were mainly seen in structural properties such as bone mineral density and bone volume density. However, the effects in femora were superior to effects in vertebrae. Ostarine treatment for 5weeks did not improve significantly biomechanical properties. mRNA expression of the receptor activator of NF-B ligand decreased after treatment, and uterine weight increased. Serum levels of phosphorus increased following ostarine treatment in intermediate and high-dose groups. Short-term treatment of osteoporotic bone with ostarine leads to improvement of several microstructural bone indices. While we did not observe changes in biomechanics, it is conceivable that longer treatment may also improve biomechanical properties. Further studies are needed to characterize longer time effects and side effects of ostarine in osteoporosis.