Actions of thyroid hormones in bone.
Thyroid hormones are required for skeletal development and establishment of peak bone mass. Hypothyroidism in children results in growth retardation with delayed skeletal development, whereas thyrotoxicosis accelerates bone maturation. In adults, T(3) regulates bone turnover and bone mineral density, and normal euthyroid status is essential to maintain optimal bone strength. Population studies indicate that hypothyroidism and hyperthyroidism are both associated with an increased risk of fracture. Nevertheless, the mechanism of T(3) action in bone is incompletely understood. Studies in mutant mice have demonstrated that T(3) action in bone is mediated principally by T(3) receptor alpha (TRalpha). T(3) exerts anabolic actions during growth to stimulate peak bone mass acrrual, but has catabolic effects on the adult skeleton that increase bone turnover. Recent studies have also suggested that TSH may have direct actions in bone cells, but such effects are difficult to resolve in vivo because thyroid hormone and TSH concentrations are maintained in an inverse relationship by the hypothalamic-pituitary-thyroid axis. Current understanding is based on studies in mice that harbor germline mutations in the genes encoding TRalpha, TRbeta or the TSH receptor and it is not clear whether the skeletal effects of these mutations result from disruption of primary T(3) actions in bone cells or whether they are secondary to systemic effects on other endocrine pathways that regulate skeletal development and bone mass. Tissue-specific disruption of thyroid hormone signalling in bone cells will be required to address this issue. Such studies are likely to identify key components of the T(3) signalling pathway that may represent suitable drug targets for treatment of osteoporosis.
Williams
Graham R
GR
Department of Medicine & MRC Clinical Sciences Centre, Imperial College London, UK. graham.williams@imperial.ac.uk
D000328:Adult; D000818:Animals; D015519:Bone Density / Q000502:physiology; D001846:Bone Development / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism*; D002648:Child; D006801:Humans; D051379:Mice; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000378:metabolism; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism
D011989:Receptors, Thyrotropin; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013972:Thyrotropin