Anselmo S. Moriscot

Antonio C. Bianco

Antonio G. Soares

Cecilia H. A. Gouveia

Fatima R. S. Freitas

Gregory A. Brent

Marisa Passarelli

Thomas S. Scanlan

Vanda Jorgetti

Thyrotoxicosis is frequently associated with increased bone turnover and decreased bone mass. To investigate the role of thyroid hormone receptor-β (TRβ) in mediating the osteopenic effects of triiodothyronine (T3), female adult rats were treated daily (64 days) with GC-1 (1.5 μg/100 g body wt), a TRβ-selective thyromimetic compound. Bone mass was studied by dual-energy X-ray absorptiometry of several skeletal sites and histomorphometry of distal femur, and the results were compared with T3-treated (3 μg/100 g body wt) or control animals. As expected, treatment with T3significantly 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 &lt; 0.05) and cholesterol (–21% vs. control, P &lt; 0.05). The histomorphometric analysis of the distal femur indicated that T3but not GC-1 treatment reduced the trabecular volume, thickness, and number. We conclude that chronic, selective activation of the TRβ isoform does not result in bone loss typical of T3-induced thyrotoxicosis, suggesting that the TRβ isoform is not critical in this process. In addition, our findings suggest that the development of TR-selective T3analogs that spare bone mass represents a significant improvement toward long-term TSH-suppressive therapy.</jats:p

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AJP Endocrinology and Metabolism

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

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

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