Department of Trauma Surgery, Orthopaedics and Plastic Surgery, University Medical Center Goettingen, Robert-Koch St. 40, 37075, Goettingen, Germany.
Division of Infection Control and Infectious Diseases, Georg-August-University of Goettingen, Humboldtallee 34A, 37073, Goettingen, Germany.
J Endocrinol Invest. 2022 Dec;45(12):2299-2311. doi: 10.1007/s40618-022-01865-9. Epub 2022 Jul 22.
Enobosarm (EN), a selective androgen receptor modulator and raloxifene (RAL), a selective estrogen receptor modulator, have been shown to improve bone tissue in osteoporotic males. The present study evaluated the effects of a combination therapy of EN and RAL on bone properties in orchiectomized rats compared to the respective single treatments.
Eight-month-old male Sprague-Dawley rats were either left intact (Non-Orx) or orchiectomized (Orx). The Orx rats were divided into four groups (n = 15 each): 1) Orx, 2) EN treatment (Orx + EN), 3) RAL treatment (Orx + RAL), 4) combined treatment (Orx + EN + RAL). EN and RAL (0.4 mg and 7 mg/kg body weight/day) were applied immediately after Orx with a soy-free pelleted diet for up to 18 weeks. The lumbar spine and femora were examined by micro-CT, biomechanical, histomorphological, ashing, and gene expression analyses.
EN exhibited an anabolic effect on bone, improving some of its parameters in Orx rats, but did not affect biomechanical properties. RAL exhibited antiresorptive activity, maintaining the biomechanical and trabecular parameters of Orx rats at the levels of Non-Orx rats. EN + RAL exerted a stronger effect than the single treatments, improving most of the bone parameters. Liver weight increased after all treatments; the kidney, prostate, and levator ani muscle weights increased after EN and EN + RAL treatments. BW was reduced due to a decreased food intake in the Orx + RAL group and due a reduced visceral fat weight in the Orx + EN + RAL group.
The EN + RAL treatment appeared to be promising in preventing male osteoporosis, but given the observed side effects on liver, kidney, and prostate weights, it requires further investigation.
选择性雄激素受体调节剂恩诺昔（EN）和选择性雌激素受体调节剂雷洛昔芬（RAL）已被证明可改善骨质疏松男性的骨组织。本研究评估了与各自的单一治疗相比，EN 和 RAL 联合治疗对去势大鼠骨特性的影响。
8 月龄雄性 Sprague-Dawley 大鼠被分为完整组（Non-Orx）或去势组（Orx）。去势大鼠再分为 4 组（每组 15 只）：1）Orx，2）EN 治疗组（Orx+EN），3）RAL 治疗组（Orx+RAL），4）联合治疗组（Orx+EN+RAL）。EN 和 RAL（0.4mg 和 7mg/kg 体重/天）在去势后立即应用，并给予不含大豆的颗粒饮食，持续 18 周。使用 micro-CT、生物力学、组织形态学、灰化和基因表达分析检测腰椎和股骨。
EN 对骨具有合成代谢作用，改善了去势大鼠的部分骨参数，但不影响生物力学性能。RAL 具有抗吸收作用，使去势大鼠的生物力学和小梁参数保持在非去势大鼠的水平。EN+RAL 比单一治疗的效果更强，改善了大多数骨参数。所有治疗后肝脏重量增加；EN 和 EN+RAL 治疗后肾脏、前列腺和提肛肌重量增加。由于 Orx+RAL 组食物摄入量减少和 Orx+EN+RAL 组内脏脂肪重量减少，BW 降低。
EN+RAL 治疗似乎有望预防男性骨质疏松症，但鉴于观察到的对肝脏、肾脏和前列腺重量的副作用，还需要进一步研究。
