|Baliram, Ramkumarie -|
|Sun, Li -|
|Li, Jianhua -|
|Latif, Rauf -|
|Huber, Amanda -|
|Yuen, Tony -|
|Blair, Harry -|
|Zaidi, Mone -|
|Davies, Terry -|
Submitted to: Journal of Clinical Investigation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 26, 2012
Publication Date: October 1, 2012
Repository URL: http://handle.nal.usda.gov/10113/56709
Citation: Baliram, R., Sun, L., Cao, J.J., Li, J., Latif, R., Huber, A.K., Yuen, T., Blair, H.C., Zaidi, M., Davies, T.F. 2012. Hyperthyroid-associated osteoporosis is exacerbated by the loss of TSH signaling. Journal of Clinical Investigation. 122(10):3737-3741. Interpretive Summary: Hyperthyroidism is accompanied by worsening osteoporosis. Elevated thyroid hormone levels are a major contributor of the bone loss in hyperthyroidism. Serum thyroid hormone suppresses the production of thyroid stimulating hormone (TSH). TSH is low in hyperthyroid states and directly affects bone metabolism. Mice lacking the TSH receptor (TSHR) have significant bone loss. We show that TSHR-deficient mice have greater bone loss in hyperthyroid state than wild type controls. Our data suggest that TSH plays an important role in bone metabolism and suppression of TSH to very low levels may induce bone loss in humans.
Technical Abstract: 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.