Abstract

Analysis of mice harbouring deletions or mutations of T₃ receptor α (TRα) and β (TRβ) have clarified the complex relationship between central and peripheral thyroid status and emphasised the essential but contrasting roles of T₃ in skeletal development and adult bone. These studies indicate that TRα1 is the predominant TR expressed in bone and that T₃ exerts anabolic actions during growth but catabolic actions in the adult skeleton. Examination of key skeletal regulatory pathways in TR mutant mice has identified GH, IGF-1 and fibroblast growth factor signalling and the Indian hedgehog/parathyroid hormone-related peptide feedback loop as major targets of T₃ action in chondrocytes and osteoblasts. Nevertheless, although increased osteoclastic resorption is a major feature of thyrotoxic bone loss and altered osteoclast activity is central to the skeletal phenotype of TR mutant mice, it remains unclear whether T₃ has direct actions in osteoclasts. Detailed future analysis of the molecular mechanisms of T₃ action in bone will enhance our understanding of this emerging field and has the potential to identify novel strategies for the prevention and treatment of osteoporosis.