Geriatric Research, Education & Clinical Center, VA Medical Center, Gainesville, FL 32608, USA.
Bone. 2012 Oct;51(4):667-73. doi: 10.1016/j.bone.2012.07.008. Epub 2012 Jul 24.
Testosterone enanthate (TE) administration attenuates bone loss in orchiectomized (ORX) rats. However, testosterone administration may increase risk for prostate/lower urinary tract related adverse events and polycythemia in humans. Trenbolone enanthate (TREN) is a synthetic testosterone analogue that preserves bone mineral density (BMD) and results in less prostate enlargement than testosterone in young ORX rodents. The purpose of this experiment was to determine if intramuscular TREN administration attenuates bone loss and maintains bone strength, without increasing prostate mass or hemoglobin concentrations in skeletally mature ORX rodents. Forty, 10 month old male F344/Brown Norway rats were randomized into SHAM, ORX, ORX+TE (7.0mg/week), and ORX+TREN (1.0mg/week) groups. Following surgery, animals recovered for 1 week and then received weekly: vehicle, TE, or TREN intramuscularly for 5 weeks. ORX reduced total and trabecular (t) BMD at the distal femoral metaphysis compared with SHAMs, while both TREN and TE completely prevented these reductions. TREN treatment also increased femoral neck strength by 28% compared with ORX animals (p<0.05), while TE did not alter femoral neck strength. In addition, TE nearly doubled prostate mass, compared with SHAMs (p<0.05). Conversely, TREN induced a non-significant 20% reduction in prostate mass compared with SHAMs, ultimately producing a prostate mass that was 64% below that found in ORX+TE animals (p<0.01). Hemoglobin concentrations and levator ani/bulbocavernosus (LABC) muscle mass were elevated in ORX+TE and ORX+TREN animals to a similar degree above both SHAM and ORX conditions (p<0.01). In skeletally mature rodents, both high-dose TE and low-dose TREN completely prevented the ORX-induced loss of tBMD at the distal femoral metaphysis and increased LABC mass. TREN also augmented femoral neck strength and maintained prostate mass at SHAM levels. These findings indicate that TREN may be an advantageous agent for future clinical trials evaluating agents capable of preventing bone loss resulting from androgen deficiency.
庚酸睾酮（TE）的给药可减轻去势（ORX）大鼠的骨质流失。然而，睾酮给药可能会增加前列腺/下尿路相关不良事件和红细胞增多症的风险，在人类中。庚酸替勃龙（TREN）是一种合成睾酮类似物，可保持骨密度（BMD），并导致年轻 ORX 啮齿动物的前列腺增大少于睾酮。本实验的目的是确定肌肉内 TREN 给药是否能减轻骨质流失并保持骨强度，而不会增加骨骼成熟的 ORX 啮齿动物的前列腺质量或血红蛋白浓度。四十只，10 个月大的 F344/布朗挪威雄性大鼠被随机分为 SHAM、ORX、ORX+TE（7.0mg/周）和 ORX+TREN（1.0mg/周）组。手术后，动物恢复 1 周，然后每周接受以下治疗：载体、TE 或 TREN 肌肉内注射 5 周。与 SHAMs 相比，ORX 降低了远端股骨干骺端的总骨密度（TBMD）和小梁骨密度（tBMD），而 TREN 和 TE 完全阻止了这些降低。与 ORX 动物相比，TREN 治疗还使股骨颈强度增加了 28%（p<0.05），而 TE 并未改变股骨颈强度。此外，TE 使前列腺质量增加了近两倍，与 SHAMs 相比（p<0.05）。相反，与 SHAMs 相比，TREN 使前列腺质量降低了 20%，最终使前列腺质量比 ORX+TE 动物低 64%（p<0.01）。血红蛋白浓度和会阴肌/球海绵体肌（LABC）肌肉质量在 ORX+TE 和 ORX+TREN 动物中升高，均高于 SHAM 和 ORX 条件（p<0.01）。在骨骼成熟的啮齿动物中，高剂量 TE 和低剂量 TREN 完全阻止了 ORX 诱导的远端股骨干骺端 tBMD 丢失，并增加了 LABC 质量。TREN 还增强了股骨颈强度，并使前列腺质量保持在 SHAM 水平。这些发现表明，TREN 可能是未来评估预防雄激素缺乏引起的骨质流失的试验的有利药物。
