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选择性雄激素受体调节剂 Ostarine 可改善去卵巢大鼠的骨愈合。

The Selective Androgen Receptor Modulator Ostarine Improves Bone Healing in Ovariectomized Rats.

机构信息

Department of Trauma Surgery, Orthopaedics and Plastic Surgery, University Medical Center Goettingen, Robert-Koch Str. 40, 37075, Goettingen, Germany.

出版信息

Calcif Tissue Int. 2020 Feb;106(2):147-157. doi: 10.1007/s00223-019-00613-1. Epub 2019 Sep 17.

DOI:10.1007/s00223-019-00613-1
PMID:31531719
Abstract

Non-steroidal selective androgen receptor modulators, including ostarine, have been developed as an alternative to steroidal hormones. Ostarine has shown a beneficial effect on bone in experimental studies, but no data regarding the effect of ostarine on bone healing have yet been reported. We investigated effects of ostarine on bone healing in ovariectomized rats. Sprague-Dawley rats (3 months old) were ovariectomized (Ovx, n = 46) or left intact (Non-Ovx, n = 10). After 8 weeks, an osteotomy of the tibia metaphysis was created in all rats, and the Ovx rats were divided into four groups: untreated Ovx (n = 10) and three Ovx groups (each of 12 rats) treated with ostarine at doses of 0.04, 0.4, or 4 mg/kg BW (OS-0.04, OS-0.4, and OS-4 groups). Five weeks later, bone healing was analyzed. The OS-4 dose enhanced callus formation, increased callus density, accelerated bridging time of the osteotomy, and elevated alkaline phosphatase gene expression in callus and its protein expression in serum. In the Ovx group, most of the callus parameters were diminished. All OS treatments increased the weight of the gastrocnemius muscle, but only partly enhanced uterus weight in OS-0.4 and OS-4. Serum cholesterol level was reduced, and serum phosphorus was elevated in OS-0.04 and OS-4. Ostarine appeared to have a positive effect on early bone healing in ovariectomized rats. Considering its favorable effect on non-osteotomized bone and muscle, this treatment could be further explored as a therapy for osteoporosis. However, possible metabolic side effects should first be evaluated.

摘要

非甾体类选择性雄激素受体调节剂,包括 Ostarine,已被开发为甾体激素的替代品。在实验研究中,Ostarine 对骨骼有有益的影响,但尚未有关于 Ostarine 对骨愈合影响的数据报道。我们研究了 Ostarine 对去卵巢大鼠骨愈合的影响。Sprague-Dawley 大鼠(3 个月龄)行卵巢切除术(Ovx,n=46)或假手术(Non-Ovx,n=10)。8 周后,所有大鼠均行胫骨干骺端截骨术,Ovx 大鼠分为 4 组:未治疗 Ovx(n=10)和 3 个 Ostarine 治疗组(每组 12 只大鼠),剂量分别为 0.04、0.4 或 4mg/kg BW(OS-0.04、OS-0.4 和 OS-4 组)。5 周后,分析骨愈合情况。OS-4 剂量促进骨痂形成,增加骨痂密度,加速截骨桥接时间,并提高骨痂碱性磷酸酶基因表达及其在血清中的蛋白表达。在 Ovx 组中,大多数骨痂参数均降低。所有 OS 治疗均增加了比目鱼肌重量,但只有 OS-0.4 和 OS-4 部分增加了子宫重量。血清胆固醇水平降低,血清磷升高。Ostarine 似乎对去卵巢大鼠早期骨愈合有积极影响。考虑到其对未截骨的骨骼和肌肉的有利作用,这种治疗方法可以进一步探索作为骨质疏松症的治疗方法。但是,首先应该评估可能的代谢副作用。

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