Androgen therapy does not prevent bone loss and arterial calcifications in male rats with CKD.

Patients suffering from chronic kidney disease (CKD) often experience bone loss and arterial calcifications. It is unclear if hypogonadism contributes to the development of these complications, and whether androgen therapy might prevent them. Male adult rats were randomized into 4 groups. The first group received standard chow (Control), while three other groups were fed a 0.25% adenine/low vitamin K diet (CKD). Two CKD groups were treated with testosterone (T) or dihydrotestosterone (DHT), whereas the control group and one CKD group received vehicle (VEH). CKD animals had 10-fold higher serum creatinine and more than 15-fold higher PTH-levels compared to controls. Serum T levels were more than 2-fold lower in the CKD-VEH group compared to Control-VEH and CKD-T groups. Seminal vesicle weight was reduced by 50% in CKD-VEH animals, and restored by T and DHT. CKD animals showed a low bone mass phenotype with decreased trabecular bone volume fraction and increased cortical porosity, which was not rescued by androgen treatment. Aortic calcification was much more prominent in CKD animals and not unequivocally prevented by androgens. Messenger RNA expression of the androgen receptor-responsive genes Acta1 and Col1a1 was reduced by CKD and stimulated by androgen treatment in levator ani muscle, but not in bone or aortic tissue. We conclude that adenine-induced CKD results in the development of hypogonadism in male rats. Androgen therapy is effective in restoring serum T levels and androgen-sensitive organ weights, but does not prevent bone loss or arterial calcifications, at least not in the presence of severe hyperparathyroidism.