Androgens, But Not Mechanical Loading, Attenuate Bone Loss And High-turnover Osteopenia In Orchiectomized Rats

Abstract

Supraphysiologic testosterone (T) administration attenuates high turnover osteopenia in orchiectomized (ORX) rats; however, this treatment results in undesirable increases in prostate mass. Trenbolone enanthate (TREN) is a highly anabolic synthetic T analogue which purportedly induces less prostate enlargement than T. PURPOSE: Determine if TREN prevents bone loss and prostate enlargement in middle-aged ORX rats and compare the bone protective effects of TREN to that induced by mechanical overload. METHODS: Ten month old male Brown Norway/F344 rats (n = 10/group) were randomized into Sham surgery, ORX, ORX+weighted ladder climbing (EX), ORX+T (7.0mg/week), and ORX+TREN (1.0mg/week) groups. All animals freely ambulated, while the EX group also completed progressively overloaded 1m ladder climbs (5 climbs × 3 days/week). Animals were sacrificed 42 days following surgery, blood was acquired to measure bone formation (osteocalcin) and resorption (Trap5b), prostates were removed and weighed, and the femurs were prepped for pQCT to determine bone characteristics at the femoral metaphysis. Differences were evaluated by ANOVA. RESULTS: ORX and ORX+EX resulted in a 71% reduction in prostate mass compared to SHAMs (p<0.05). ORX+TREN treatment reduced prostate mass by 20% compared with SHAMs, while ORX+T treatment nearly doubled prostate mass (p<0.05). ORX increased serum osteocalcin by 34% and Trap5b by 13%, and reduced trabecular bone mineral content (tBMC) and bone mineral density (tBMD), and cortical (c)BMD compared with SHAMs (p<0.05). ORX+EX prevented the ORX-induced change in osteocalcin (p<0.05), but did not prevent the increase in Trap5b or ORX-induced bone loss. Conversely, ORX+TREN and ORX+T treatments induced a similar 40% and 51% reduction in osteocalcin and a 37-43% reduction in Trap5b compared with ORX (p<0.05), while maintaining tBMC, tBMD, and cBMD at the level of SHAMs, demonstrating a prevention of ORX-induced high-turnover osteopenia. CONCLUSION: In the absence of endogenous androgens, mechanical overload fails to prevent bone loss. As such, TREN appears to be a suitable agent for further pre-clinical trials intended to prevent hypogonadism-induced bone loss based on its ability to prevent bone loss and beneficially reduce prostate mass. Supported by a VA Merit Award (SEB).