The main goal of the proposed research is a better understanding of the effects of high phosphorus (Pi) intake on calcium (Ca) and bone metabolism. This concern arises from our present dietary pattern of high Pi-low Ca intake, due in part to the growing use of phosphate-containing food additives. This dietary pattern is most pronounced in youth and may influence the total bone mass they achieve at maturity. Our key objective is to determine how high Pi consumption influences the secretory response of the parathyroid glands in young adults and growing dogs.
Our specific aims are to: 1) Verify that oral loads of phosphate salt stimulate both parathyroid hormone (PTH) secretion and indexes of PTH action on kidney in young adults; 2) Determine the influence of a Pi load administered as a meal on the human diurnal secretory pattern of PTH and the hormone's action on kidney; 3) Determine if young adults adapt to chronic high Pi intake through changes in PTH secretion, PTH-regulated renal activity, and vitamin D metabolism; 4) Determine if the growing dog has a detectable increase in PTH secretion and phosphaturia in response to a Pi load consumed as a meal; 5) Develop the growing dog as a model to assess the effects of a low Ca, high Pi diet, comparable to current human intakes, on skeletal mass achieved at muturity. Unlike previous studies, the proposed work integrates well-established, sensitive assays for PTH and indexes of PTH-renal activity with adequate and carefully controlled diets, and monitors these physiological responses throughout the diurnal cycle. The study will determine if this low Ca, high Pi dietary pattern has the potential to decrease maximal skeletal mass achieved at muturity. Any nutritional factor that reduces maximal bone mass predisposes and individual to clinically significant osteoporosis later in life. Understanding of how high Pi intake influences PTH secretion is essential to the establishment of dietary recommendations for an optimal Ca:Pi ratio and the implementation of early nutrition intervention that could maximize adult skeletal mass and reduce the incidence of osteoporotic fractures with increasing age.
