methimazole and Bone-Diseases--Metabolic

The osteoporosis associated with human hyperthyroidism has traditionally been attributed to elevated thyroid hormone levels. There is evidence, however, that thyroid-stimulating hormone (TSH), which is low in most hyperthyroid states, directly affects the skeleton. Importantly, Tshr-knockout mice are osteopenic. In order to determine whether low TSH levels contribute to bone loss in hyperthyroidism, we compared the skeletal phenotypes of wild-type and Tshr-knockout mice that were rendered hyperthyroid. We found that hyperthyroid mice lacking TSHR had greater bone loss and resorption than hyperthyroid wild-type mice, thereby demonstrating that the absence of TSH signaling contributes to bone loss. Further, we identified a TSH-like factor that may confer osteoprotection. These studies suggest that therapeutic suppression of TSH to very low levels may contribute to bone loss in people.

Topics: Animals; Bone Density; Bone Diseases, Metabolic; Bone Resorption; Dose-Response Relationship, Drug; Drug Implants; Hormone Replacement Therapy; Hyperthyroidism; Hypothyroidism; Methimazole; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteoporosis; Phenotype; Receptors, Thyrotropin; Signal Transduction; Thyrotropin; Thyroxine