Thyrotoxicosis is frequently associated with increased bone turnover and decreased bone mass. In order to investigate the role of thyroid hormone receptor beta (TR) in mediating the osteopenic effects of triiodothyronine (T3), female adult rats were treated daily (64 days) with GC-1 (1.5 µg/100 g BW), a TR-selective thyromimetic compound. Bone mass was studied by dual energy X-ray absorptiometry of several skeleton sites and histomorphometry of distal femur, and the results compared with T3-treated (3 µg/100 g BW) or control animals. As expected, treatment with T3 significantly reduced bone mineral density (BMD) in the lumbar vertebrae (L2-L5), femur and tibia by 10-15 %. In contrast, GC-1 treatment did not affect the BMD in any of the skeletal sites studied. The efficacy of GC-1 treatment was verified by a reduction in serum TSH (-52 % vs. control, p < 0.05) and cholesterol (-21 % vs. control, p < 0.05). The histomorphometric analysis of the distal femur indicated that T3- but not GC-1-treatment reduced the trabecular volume, thickness and number. We conclude that chronic, selective activation of the TRisoform does not result in bone loss typical of T3-induced thyrotoxicosis, suggesting that the TR isoform is not critical in this process. In addition, our findings suggest that the development of TR-selective T3 analogs that spare bone mass represents a significant improvement towards long-term TSH suppressive therapy.