title: Hyperthyroid-associated osteoporosis is exacerbated by the loss of TSH signaling.
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.
authors.affiliation: Thyroid Research Unit and The Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, and James J. Peters VA Medical Center, New York, New York 10029, USA.
authors.forename: Ramkumarie
authors.initials: R
authors.lastname: Baliram
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Jay
authors.initials: J
authors.lastname: Cao
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
authors.forename: Rauf
authors.initials: R
authors.lastname: Latif
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Huber
authors.forename: Tony
authors.initials: T
authors.lastname: Yuen
authors.forename: Harry C
authors.initials: HC
authors.lastname: Blair
authors.forename: Mone
authors.initials: M
authors.lastname: Zaidi
authors.forename: Terry F
authors.initials: TF
authors.lastname: Davies
mesh_terms: D000818:Animals; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000235:genetics; D001862:Bone Resorption / Q000097:blood / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D020249:Hormone Replacement Therapy; D006980:Hyperthyroidism / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D007037:Hypothyroidism / Q000097:blood / Q000139:chemically induced; D008713:Methimazole / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010024:Osteoporosis / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D010641:Phenotype; D011989:Receptors, Thyrotropin / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction; D013972:Thyrotropin / Q000097:blood / Q000172:deficiency / Q000502:physiology*; D013974:Thyroxine / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D004343:Drug Implants; D011989:Receptors, Thyrotropin; D008713:Methimazole; D013972:Thyrotropin; D013974:Thyroxine