The influence of dietary calcium and phosphorus on bone metabolism

By means of this study it was attempted to obtain a better insight into the possible influence of the diet on the development of human osteoporosis. This disease, which is a consequence of decalcification of the bones, occurs frequently in elderly people, particularly in postmenopausal women. On the basis of data from the literature a model was composed describing a mechanism according to which either a low-calcium diet, a high-phosphorus diet or a diet with a low calcium-to-phosphorus ratio (temporarily) decreases the plasma-ionized calcium concentration, so that the parathyroid glands are stimulated to secrete parathyroid hormone (PTH). This hormone acts on bone and kidney in order to restore the plasma-ionized calcium concentration, which may proceed at the expense of skeletal calcium, so that osteoporosis develops. The model explains why the dietary stimulation of PTH secretion occurs especially when the renal function has decreased and/or when a suboptimal vitamin D status is prevalent. In an observational cross-sectional study in elderly people and in three experimental studies with three month old male rats, the influence of dietary calcium and phosphorus on bone metabolism was investigated. The cross-sectional study was carried out among 89 healthy eldery people (53 women and 36 men), whose age ranged from 57 to 89 years (mean: 70 years). It was investigated whether relationships could be demonstrated which fitted in the proposed model. For this purpose the calcium and phosphorus intake was estimated by the cross-cheek method. The bone mineral content (BMC) and the bone width (BW) were measured on the distal third of the radius (cortical bone) by means of 125 I-photon absorptiometry. In addition, parameters of the bone metabolism in serum and urine were estimated. Because of the observational nature of the study, which lacked an experimental basis, it was stressed that the results had to be interpreted with caution. The mean daily calcium intake of the women was 1.04 g and that of the men 1.22 g. These amounts largely exceeded the current Dutch recommended allowance for adults of 0.8 g per day. Phosphorus intake was considered to be high: 25% of the men and women had an intake of more than 1.6 and 2.0 g per day respectively. In the men as well as in the women the serum concentrations of PTH and creatinine were at the upper limit of normality. The level of this latter parameter pointed to a slightly decreased renal function such as could be expected in people of this age group. In the women the amount of cortical bone, corrected for bone width (BMC/BW-ratio) showed a significant negative correlation with age, and the regression corresponded with an annual bone loss of about 0.8%. This loss of bone was associated with a decrease of body height of about 0.35 cm per year, which was considered to be, at least in part, the consequence of vertebral collapse. The BMC/BW-ratio correlated positively with calcium intake and negatively with phosphorus intake, if differences in age, body size and either calcium or phosphorus intake were taken into account. The excretion of phosphorus with the urine also showed a negative correlation with the BMC/BW-ratio, and dietary phosphorus correlated positively with the urinary excretion of phosphorus as well as with that of hydroxyproline. The possibility was discussed that these correlations are-in line with the concept that high-phosphorus diets contribute to bone loss in that they stimulate the secretion of PTH. In the men, loss of cortical bone with advancing age was not observed, and no relations were found between dietary calcium or phosphorus and the amount of this bone. However, a marked loss of height with age (0.45 cm per year) was established and a positive correlation between dietary calcium and body height was found. It was considered that this correlation might reflect a 'protective' action of dietary calcium against loss of trabecular bone from the vertebrae. The urinary excretion of phosphorus showed a negative correlation with the serum phosphorus concentration, and dietary phosphorus correlated positively with the urinary excretion of phosphorus as well as with that of hydroxyproline. The possibility was discussed that these correlations are in line with a concept according to which high-phosphorus diets stimulate the secretion of PTH and increase the bone turnover rate, but do not bring about loss of cortical bone. In the men as well as in the women, the serum concentration of 25-hydroxy-vitamin D (25-HCC) correlated positively with the BMC/BW-ratio despite the fact that serum values of this metabolite (the serum 25-HCC concentration is used as an indicator of the vitamin D status) were within normal limits. The possibility was discussed that this positive correlation might indicate that elderly people require larger amounts of vitamin D as a consequence of diminished renal synthesis of the active vitamin D metabolite. The experiments with rats, which lasted either four, sixteen or forty-two weeks, showed that high-phosphorus (1.2 or 1.3%) diets did not significantly influence calcium retention and/or bone mass, as opposed to diets with either a low (0.15%) or a normal (0.45%) phosphorus content. From histological and chemical analyses of bone samples, it was concluded that the quality of the bone was not obviously affected by the phosphorus content (0. 15 versus 1.20%) of the diet in experiments which lasted four or sixteen weeks. However, in the experiment which lasted forty-two weeks, bone density was found to have been reduced in rats fed 1.3% dietary phosphorus, as opposed to those that had been fed 0.45% dietary phosphorus. It was suggested that the effect of high-phosphorus diets on bone depends either on age or on the duration of feeding these diets. There were consistent and strong indications that the function of the parathyroids and the bone turnover rate were stimulated in rats fed high-phosphorus diets. In addition to the diminished bone density after forty-two weeks, these indications were: decreased renal tubular reabsorption of phosphate, hypophosphataemia, decreased urinary calcium excretion, increased urinary phosphorus excretion, nephrocalcinosis and increased urinary excretion of hydroxyproline. With the exception of nephrocalcinosis and decreased urinary calcium, these biochemical changes were reduced if the calcium content of the diet was elevated. This was associated with an inhibiting effect of dietary calcium on the intestinal phosphorus absorption. In the experiments which lasted tour or sixteen weeks, the cause and consequence of nephrocalcinosis were studied in more detail. It was found that nephrocalcinosis was attributable to the deposition of calcium apatite and that it resulted in a clear but moderate loss of renal function. This loss appeared to increase slowly during the course of the experiments. The extent of nephrocalcinosis and loss of renal function depended on the calcium content of the diet. When the diet contained 1.2% phosphorus, the extent of renal calcification and loss of renal function increased if the calcium content of the diet was raised from 0.3 to 1.2%, but these parameters decreased if the calcium content of the diet was further raised to 2.4%. There were no indications as to whether the loss of renal function had any influence on the composition or metabolism of the bone. In rats fed the low-phosphorus control diets, but not in those fed the high-phosphorus diets, osteoporosis developed when the dietary Ca/P-ratio was low (0.25 or 0.50). It was concluded that this stresses the importance of indicating absolute levels of calcium and phosphorus in the diet and that reporting only the ratio between these nutrients should be avoided. The results of the cross-sectional study of elderly people and those of the experiments with rats gave rise to the framing of a hypothesis. This hypothesis explains why hyperparathyroidism, induced by excess of dietary phosphorus, brings about a decrease in the plasma phosphorus concentration in the elderly man and in the rat, whereas no such effect is seen in the postmenopausal woman. Finally, recommendations were made regarding dietary measures which are considered to be useful in the prevention of osteoporosis in western societies. These measures are: (1) ensure a proper vitamin D status, (2) restrict the intake of phosphorus, (3) take ample calcium, and (4) restrict the intake of protein. In order to reduce the intake of phosphorus and protein, it was suggested that the consumption of meat and poultry should be decreased and the consumption of products which contain added phosphates should be limited. A further discussion was concerned with a regular consumption of dairy products which is necessary to ensure a sufficient intake of calcium.