Effects of thyroid hormone administration and estrogen deficiency on bone mass of female rats.

To investigate the effects of thyroxine (T4) administration on bone mass, five 81-day-old female rats were treated with T4 (25 microg of T4/100 g of body weight [bw]/day), and bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) 28 days later. The BMD values for the total skeleton, femoral, and tibial subsegments were lower than in controls (p < or = 0.05). The lumbar spine (L2-L5) was not significantly affected by T4 treatment. Next, thirty-seven 211 +/- 1.5 (mean +/- SEM)-day-old female rats were divided into six groups as follows: (1) control; (2) ovariectomized (OVX); (3) 1xT4 (approximately 1.0 microg of T4/100 g of bw/day; approximately physiological replacement dose); (4) OVX + 1xT4; (5) 2xT4 (approximately 2.0 microg of T4/100 g of bw/day); (6) OVX + 2xT4. DXA scans were performed at days 0 and 85. Control rats showed a generalized BMD increase, as opposed to a decrease in OVX rats. The trabecular bone volume of the fifth lumbar vertebra was also lower in OVX rats than in controls (p < 0.05). The 1xT4 treatment had no effect on BMD of intact rats, while treatment with 2xT4 impaired the expected BMD increase. Unexpectedly, the OVX + 1xT4 group presented a generalized BMD increase that was significant for the total skeleton, L2-L5, and femoral subsegments (p < 0.05), comparable to controls. Treating OVX animals with 2xT4 did not potentiate the osteopenic effects of estrogen deficiency, nor did it reverse the osteopenic effects of OVX. In conclusion, treatment with high doses of T4 caused BMD to decrease substantially, particularly at the femur, whereas near physiological doses of T4 prevented bone loss associated with OVX, and regardless of bone type (trabecular or cortical), the skeleton site seems to be a more important determinant of the effects of thyroid hormone on bone mass.