AROMATIZATION OF ANDROGENS IS IMPORTANT FOR SKELETAL MAINTENANCE OF AGED MALE-RATS

A nonsteroidal aromatase inhibitor vorozole (VOR) was administered to aged (12 months old) male Wistar rats and its effect was compared with the effect of androgen deficiency. The rats were either sham-operated (SHAM) or orchidectomized (ORCH) and treated with or without VOR. Thu s, four experimental groups were created (SHAM, ORCH, SHAM + VOR, ORCH + VOR). The follow-up period was 4 months. At the end of the experime ntal period, bone mineral density (BMD) of the first four lumbar verte brae and right femur was measured ex vivo with dual-energy X-ray absor ptiometry, bone formation was evaluated by serum osteocalcin, and bone resorption by urinary excretion of (deoxy)pyridinoline. Orchidectomy increased bone resorption 2- to 3-fold whereas bone formation was only slightly increased. Treatment of intact male rats with VOR also incre ased bone resorption (+30% increase) whereas bone formation was not in creased in this SHAM + VOR group. Their BMD was 7% lower in the femur (P < 0.01) and 6% lower in the lumbar vertebrae (P < 0.01) compared wi th the SHAM group that had not received VOR. Moreover, this decrease o f bone mineral density was not significantly different from the expect ed decrease of bone density observed in the ORCH groups (6-10%). This was also reflected by a decrease of calcium content of the first four lumbar vertebrae of 15% (P < 0.001) in the SHAM + VOR group and 9-14% (P < 0.05) in the ORCH groups compared with the SHAM group, respective ly. These data therefore suggest that inhibition of aromatization of a ndrogens into estrogens increases bone resorption and bone loss simila r to that observed after complete removal of androgens. Aromatization of androgens into estrogens may therefore, at least partly, explain th e effects of androgens on skeletal maintenance.