Cortical bone loss in androgen-deficient aged male rats is mainly caused by increased endocortical bone remodeling.
BACKGROUND
Hypogonadism is considered to be one of the major risk factors for osteoporosis in men. Here, we sequentially studied the effects of androgen deficiency on cortical bone in aged orchiectomy (ORX) rats.


METHODS
One hundred seventy 13-mo-old male Fischer-344 rats were either ORX or sham-operated. After in vivo fluorochrome labeling, groups of 8-15 SHAM and ORX rats each were killed at 2 wk and 1, 2, 3, 4, 6, and 9 mo after surgery. To examine the effects of testosterone replacement therapy, 9-mo-old ORX rats were supplemented with testosterone undecanoate at a weekly dose of 6 mg/kg for 4 mo. Cortical bone changes in the tibial shaft were monitored by pQCT analysis and by bone histomorphometry.


RESULTS
SHAM rats did not show age-related bone loss at the tibial diaphysis. pQCT analysis and bone histomorphometry showed cortical bone osteopenia in ORX rats, beginning from 2 mo after surgery until the end of the study. Androgen deficiency induced a sustained decrease in periosteal bone formation during the first 4 mo after ORX. However, although periosteal expansion of the tibial shaft tended to be slower in ORX rats compared with SHAM controls, the reduction in total cross-sectional area in ORX animals reached statistical significance only at 4 mo after surgery. The major mechanism for cortical bone loss in aged ORX rats was a progressive expansion of the marrow cavity, which was associated with an initial increase in endocortical eroded perimeter at 1 and 2 mo after surgery, followed by a sustained increase in endocortical bone formation until the end of the study. All these changes were prevented in aged ORX rats receiving testosterone supplementation in an insulin-like growth factor system-independent fashion.


CONCLUSIONS
We conclude that androgen deficiency-induced cortical bone loss in aged, nongrowing rats is mainly caused by augmented endocortical bone remodeling.
Reim
Natascha S
NS
Institute of Physiology, Physiological Chemistry and Animal Nutrition, Ludwig Maximilians University, Munich, Germany.
Breig
Bianca
B
Stahr
Kerstin
K
Eberle
Johannes
J
Hoeflich
Andreas
A
Wolf
Eckhard
E
Erben
Reinhold G
RG
D000728:Androgens / Q000172:deficiency*; D000818:Animals; D015519:Bone Density; D016723:Bone Remodeling; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D000728:Androgens