Harnessing the parathyroids to create stronger bones.
OBJECTIVE
Parathyroid hormone is anabolic to bone but when secreted in excess it is catabolic. It is important, therefore, to understand the mechanisms that determine the normal circadian rhythm of parathyroid hormone secretion and whether the cellular response to it will be anabolic or catabolic. This may lead to new strategies for the treatment of osteoporosis and the low turnover bone disease of some dialysis patients.


RESULTS
The parathyroid plays a central role in normal mineral and bone homeostasis by acting on its receptor, the PTH/PTHrP receptor (PTH1R). In fact there is more than one receptor - the PTH2 receptor and a putative carboxy-terminal PTH receptor. The latter, in particular, may be particularly relevant to our understanding of the role of parathyroid hormone and its use in pharmacology. Parathyroid hormone in excess destroys bone, as in most patients with chronic renal failure, and when it is lacking this may result in low turnover bone disease. At a more subtle level, patients with postmenopausal osteoporosis may have a blunting of the normal circadian rhythm of parathyroid hormone, with its peak at night and nadir in the morning. Insights as to what determines whether parathyroid hormone will be anabolic or catabolic to bone are reviewed.


CONCLUSIONS
Attempting to correct the circadian rhythm in osteoporotic patients by calcilytic drugs or perhaps physiological equivalents may have a role in the future in treating osteoporosis. In the meantime, the administration of recombinant parathyroid hormone is an effective agent in the management of osteoporosis.
Silver
Justin
J
Minerva Center for Calcium and Bone Metabolism, Nephrology Services, Hadassah University Hospital, Jerusalem, Israel. silver@huji.ac.il
Bushinsky
David
D
D001847:Bone Diseases / Q000188:drug therapy / Q000503:physiopathology; D001862:Bone Resorption / Q000188:drug therapy / Q000503:physiopathology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002940:Circadian Rhythm / Q000502:physiology; D006801:Humans; D010006:Osteoblasts / Q000502:physiology; D010024:Osteoporosis / Q000188:drug therapy* / Q000503:physiopathology; D010280:Parathyroid Glands / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism* / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism; D018016:Receptors, Parathyroid Hormone / Q000378:metabolism*
D002121:Calcium Channel Blockers; D010281:Parathyroid Hormone; D010710:Phosphates; D018016:Receptors, Parathyroid Hormone; D002118:Calcium