FIG. 1. The major physiological regulatory mechanisms in Ca2+ metabolism.
Other hormones including thyroid and pituitary hormones, and adrenal and gonadal steroids, also have major effects on the skeleton, as seen in clinical disorders in which their secretion is abnormally high or low. Many additional factors, notably cytokines and growth factors, also play a role in skeletal metabolism, in many cases by interacting locally with systemic hormones. Mechanical loading of the skeleton is also a major influence over bone remodelling.
The genetic factors that regulate skeletal development and function are gradually being identified, and recent examples include the Cbfal gene for osteoblast differentiation and the RANK system for osteoclasts. Many cytokines and growth factors are involved in the induction of new bone formation, and the activation and modulation of remodelling. These and other mediators contribute not only to the physiological regulation of bone metabolism but also to the pathogenesis of skeletal diseases.
After skeletal growth is complete, remodelling of both cortical and trabecular bone continues and results in an annual turnover of about 10% of the adult skeleton. This requires the coordinated actions of osteoclasts to remove bone, and osteoblasts to replace it, and these processes may be monitored by histological means. Changes in the quality or amount of bone arise from disorders of bone modelling during growth or remodelling during adult life.
An excellent and comprehensive review of basic and clinical aspects of metabolic bone disease can be found in the Primer edited by Favus et al (1999).
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