Early induction of alterations in cancellous and cortical bone histology after orchiectomy in mature rats.

Androgen deficiency is associated with low bone mass in humans and animals, but the remodeling alterations that lead to bone loss are unclear. Our objective was to define early responses in both cancellous and cortical bone to orchiectomy (ORX) using histomorphometry in sexually mature (4-month-old) rats. A total of 62 male rats, 4 months of age, were divided into six groups, sham operated (SH) or orchiectomized (ORX), and sacrificed 1, 2, or 4 weeks after ORX. Calcein was given 5 and 2 days before sacrifice to label mineralizing surfaces. Bone mineral density (BMD) was measured in excised femurs by dual energy X-ray absorptiometry (DEXA). Static and dynamic histomorphometry was evaluated in the cancellous bone of the proximal tibial metaphysis and lumbar vertebral bodies, and in the cortical bone of the tibial diaphysis. Osteopenia began to develop by 2 weeks after ORX, though weight gain and femur length did not change. Femoral BMD was significantly reduced and BMC decreased (NS) by 4 weeks after ORX (p < 0.05). Tibial and vertebral cancellous bone volume decreased 19% and 13%, respectively, while osteoblast and osteoclast surfaces, and numbers of osteoclasts, increased after ORX. At 2 weeks post-ORX, an increase in cancellous bone formation rate was attributable primarily to an increase in mineralizing surfaces and a smaller rise in mineral apposition rate. In contrast, cortical bone periosteal, but not endosteal, bone formation rate and mineralizing surfaces decreased. We conclude that ORX stimulates cancellous and diminishes periosteal bone turnover rapidly after ORX, with subsequent decreases in bone volume and mineral density. The clear divergence in cortical and cancellous bone responses to hypogonadism raises important questions regarding the control of bone formation and its role in defining the skeletal phenotype.