The physiology of the circadian rhythm of parathyroid hormone and its potential as a treatment for osteoporosis

PURPOSE OF REVIEWA circadian rhythm exists for parathyroid hormone, with a biphasic pattern showing a late afternoon/early evening rise and fall and a broader, longer-lasting increase late evening/early morning reaching nadir mid-morning. This review explores the characteristics of the circadian rhythm, factors regulating the rhythm and its role in bone metabolism. RECENT FINDINGSGender differences exist in the circadian rhythm for parathyroid hormone. Ageing in women alters the response to calcium infusion, increasing the suppression of parathyroid hormone secretion and decreasing bone resorption. There is no difference between young and elderly men in the parathyroid hormone response to calcium infusion. Loop diuretic ingestion alters the parathyroid hormone circadian rhythm reflecting loop diuretic effects on phosphate and calcium metabolism. Adult growth hormone deficiency alters parathyroid hormone secretion and end organ sensitivity, but the circadian rhythm is retained. Growth hormone replacement therapy enhances the parathyroid hormone circadian rhythm and increases end organ responses. Exogenous parathyroid hormone (1-34) and (1-84) administered by daily injection has an anabolic effect on bone, increasing bone mass and decreasing fracture. Calcilytic drugs stimulate and calcimimetic drugs suppress parathyroid hormone secretion and have been used to treat disorders of bone metabolism. SUMMARYThe circadian nature of parathyroid hormone secretion is confirmed by many publications. The underlying rhythm is endogenous. Life style factors and nutritional intake modulate the pattern of secretion. Direct association with bone resorption and formation is tentative. It is suggested that acute changes in these rhythms have little effect on resorption, but longer-term manipulation of parathyroid hormone secretion alters bone cell function. Growth hormone therapy in adult deficiency increases parathyroid hormone activity, indicating growth hormone may have therapeutic potential for osteoporosis. Manipulation of the endogenous parathyroid hormone rhythm, using timed supplements of phosphate or calcium or by calcilytic and calcimimetic molecules, offers a novel approach to osteoporosis treatment.