Thyrotoxicosis is frequently associated with increased bone turn- over and decreased bone mass. To investigate the role of thyroid hormone receptor- (TR ) in mediating the osteopenic effects of triiodothyronine (T3), female adult rats were treated daily (64 days) with GC-1 (1.5 g/100 g body wt), a TR -selective thyromimetic compound. Bone mass was studied by dual-energy X-ray absorptiometry of several skeletal sites and histomor- phometry of distal femur, and the results were compared with T3-treated (3 g/100 g body wt) 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 TR isoform 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 toward long-term TSH-suppressive therapy.

Spared bone mass in rats treated with thyroid hormone receptor TR -selective compound GC-1.

Fatima R. S. Freitas, Anselmo S. Moriscot, Vanda Jorgetti, Antonio G. Soares, Marisa Passarelli, Thomas S. Scanlan, Gregory A. Brent, Antonio C. Bianco, and Cecilia H. A. Gouveia. American Journal of Physiology. July 29, 2003. doi: 10.1152/ajpendo.00506.2002

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