Calcium and Phosphate Homeostasis
Regulation of vitamin D metabolism by phosphate and FGF23 . circadian variance, effects of treatment, and relationship to parathyroid status. Endocrine Control of Calcium and Phosphate Homeostasis In concert with parathyroid hormone, vitamin D also enhances fluxes of calcium out of bone. Phosphate is found in all cells in your body and is absorbed with help from Vitamin D. Calcium is stored in your bones, and is essential for building and keeping.
For supplement users, the median dose was the same for men, women, and children: Effects of Vitamin D Deficiency Vitamin D deficiency is characterized by inadequate mineralization or demineralization of the skeleton.
In children, vitamin D deficiency results in inadequate mineralization of the skeleton causing rickets, which is characterized by widening at the end of the long bones, rachitic rosary, deformations in the skeleton including frontal bossing, and outward or inward deformities of the lower limbs causing bowed legs and knocked knees, respectively Goldring et al.
In adults, vitamin D deficiency leads to a mineralization defect in the skeleton causing osteomalacia. In addition, the secondary hyperparathyroidism associated with vitamin D deficiency enhances mobilization of calcium from the skeleton, resulting in porotic bone Favus and Christakos, Any alteration in the cutaneous production of vitamin D3, the absorption of vitamin D in the intestine, or the metabolism of vitamin D to its active form, 1,25 OH 2D, can lead to a vitamin D-deficient state Demay, ; Holick, In addition, an alteration in the recognition of 1,25 OH 2D by its receptor can also cause vitamin D deficiency, metabolic bone disease, and accompanying biochemical abnormalities Demay, Vitamin D deficiency causes a decrease in ionized calcium in blood, which in turn leads to an increase in the production and secretion of PTH Fraser, ; Holick, PTH stimulates the mobilization of calcium from the skeleton, conserves renal loss of calcium, and causes increased renal excretion of phosphorus leading to a normal fasting serum calcium with a low or low-normal serum phosphorus Holick, Thus, vitamin D deficiency is characterized biochemically by either a normal or low-normal serum calcium with a low-normal or low-fasting serum phosphorus and an elevated serum PTH.
Serum alkaline phosphatase is usually elevated in vitamin D deficiency states Goldring et al. The elevated PTH leads to an increase in the destruction of the skeletal tissue in order to release calcium into the blood.
The bone collagen by-products, including hydroxyproline, pyridinoline, deoxypyridinoline, and N-telopeptide, are excreted into the urine and are usually elevated Kamel et al. It is well recognized that vitamin D deficiency causes abnormalities in calcium and bone metabolism. The possibility that vitamin D deficiency is associated with an increased risk of colon, breast, and prostate cancer was suggested in epidemiologic surveys of people living at higher latitudes Garland et al.
At this time, it is premature to categorically suggest that vitamin D deficiency increases cancer risk. Prospective studies need to be carried out to test the hypothesis. Thus, serum 25 OH D will be used as the primary indicator of vitamin D adequacy. For example, the lower and upper limits of the normal range of 25 OH D in California will be higher than those limits in Boston Clemens and Adams, Two pathologic indicators, radiologic evidence of rickets Demay, and biochemical abnormalities associated with metabolic bone disease, including elevations in alkaline phosphatase and PTH concentrations in the circulation Demay,have been correlated with serum 25 OH D.
A 25 OH D concentration below Little information is available about the level of 25 OH D that is essential for maintaining normal calcium metabolism and peak bone mass in older children and in young and middle-aged adults. For the elderly, there is mounting scientific evidence to support their increased requirement for dietary vitamin D in order to maintain normal calcium metabolism and maximize bone health Dawson-Hughes et al. Therefore, the serum 25 OH D concentration was utilized to evaluate vitamin D deficiency in this age group, but it was not the only indicator used to determine the vitamin D reference value for the elderly.
It is likely that increased melanin pigmentation which decreases the cutaneous production of vitamin D and the lack of dietary vitamin D due to a high incidence of lactose intolerance are the contributing causes for this. This hormone's serum concentrations are tightly regulated by a variety of factors, including circulating levels of serum calcium, phosphorus, parathyroid hormone, and other hormones Fraser, ; Holick, Evaluation of Skeletal Health The ultimate effect of vitamin D on human health is maintenance of a healthy skeleton.
Thus, in reviewing the literature for determining vitamin D status, one of the indicators that has proven to be valuable is an evaluation of skeletal health. In neonates and children, bone development and the prevention of rickets, either in combination with serum 25 OH D and PTH concentrations, or by itself, are good indicators of vitamin D status Gultekin et al.
Recommendations for Adequate Intake The recommendation for how much vitamin D is required to maintain adequate calcium metabolism and good bone health for all ages may be considered the easiest, as well as at times the most difficult, to determine. Humans of all ages, races, and both sexes can obtain all of their body's requirement for vitamin D through exposure to an adequate amount of sunlight. However, the sunlight- mediated synthesis of vitamin D in the skin is profoundly affected by a wide variety of factors, including degree of skin pigmentation, latitude, time of day, season of the year, weather conditions, and the amount of body surface covered with clothing or sunscreen Holick, Therefore, it is very difficult to determine an accurate value for an Estimated Average Requirement EAR as most of the studies are subject to one or more of these variables, especially exposure to sunlight, which is difficult to quantitate.
Vitamin D is a hormone, and therefore, when considering the requirements for vitamin D, EARs would represent gross estimates of the need for the active hormone. The only studies that provide an approximation of how much vitamin D is required to maintain an individual's serum 25 OH D concentration above that associated with abnormalities in BMD are ones that have been conducted in the winter at far northern and southern latitudes where exposure to sunlight does not produce any significant quantities of vitamin D Ladizesky et al.
Phosphorus in Your Diet
However, these studies still do not account for subjects' exposure to sunlight in the spring, summer, and fall when the cutaneous synthesis of vitamin D occurs and it is stored in the body fat for use in the winter. Another limitation of the reported studies is the assumption made regarding the vitamin D content of various foods. Despite government mandates for vitamin D fortification of milk in both the United States and Canada, actual analysis has shown this fortification to be highly variable Chen et al.
Furthermore, the amount of vitamin D found naturally in foods, such as fish liver oils, fatty fish, and egg yolks, is very dependent on the time of the year these foods are harvested.
The control of calcium and phosphorus metabolism by the vitamin D endocrine system.
Studies that report the dietary intake of vitamin D based on the expected amount of vitamin D fortification of milk, margarine, cereals, and breads are highly suspect because the analysis of the vitamin D content in the foods at the time of the studies may have been either inadequate or not determined Chen et al. Although dietary intake studies rarely conduct simultaneous analysis of the chemical composition of food, it is assumed that the data in the food composition database are adequate.
Infants aged 0 to 6 months who are born in the late fall in far northern and southern latitudes can only obtain vitamin D from their own stores, which have resulted from transplacental transfer in utero, or from that provided by the diet, including mother's breast milk, infant formula, or supplements. Because human milk has very little vitamin D, breast-fed infants who are not exposed to sunlight are unlikely to obtain adequate amounts of vitamin D from mother's milk to satisfy their needs beyond early infancy Nakao, ; Specker et al.
Therefore, an Adequate Intake AI for infants ages 0 through 12 months is based on the lowest dietary intake of vitamin D that has been associated with a mean serum 25 OH D concentration greater than 2.
Further, it is assumes no exogenous source of vitamin D from sunlight exposure.
Children aged 1 through 18 years and most adults obtain some of their vitamin D requirement from sunlight exposure. Since the issue of sunlight exposure confounds the literature, intake data are not available to determine an EAR, a true estimated average requirement, that can be strongly supported as a value at which half of the population group for which it is derived would be at increased risk of inadequate serum 25 OH D.
In addition, no studies have evaluated how much vitamin D is required to maintain normal blood levels of 25 OH D and PTH in children or adults who have been deprived of sunlight and dietary vitamin D for a period of more than 6 months. Because sufficient scientific data are not available to estimate an EAR, an AI will be the reference value developed for vitamin D. The AI represents the intake that is considered likely to maintain adequate serum 25 OH D for individuals in the population group who have limited but uncertain sun exposure and stores, multiplied by a safety factor of percent for those unable to obtain sunlight.
When consumed by an individual, the AI is sufficient to minimize the risk of low serum 25 OH D and may actually represent an overestimate of true biological need. The recommended AI assumes that no vitamin D is available from sun-mediated cutaneous synthesis. This synthesis is especially important for calcium metabolism and bone health for the very young and for older adults.
It is well documented that infants and young children who live in far northern latitudes are at high risk for developing rickets Lebrun et al. At the other end of the age spectrum, older adults are more prone to developing vitamin D deficiency Holick et al. Indeed, vitamin D deficiency is now a significant concern in adults over the age of 50 years who live in the northern industrialized cities of the world Dawson-Hughes et al.
The vitamin D available to the infant during the first 6 months of life depends initially on the vitamin D status of the mother during pregnancy and later on the infant's exposure to sunlight and diet. In a population of 25 Caucasian and African American women who had a mean vitamin D intake of Women consuming 15 to Although maternal vitamin D intake is associated with the vitamin D content of human milk, the latter is not correlated with the infant's serum 25 OH D concentrations, due to the overwhelming effect of sunlight exposure on the infant's vitamin D status Ala-Houhala, ; Ala-Houhala et al.
The control of calcium and phosphorus metabolism by the vitamin D endocrine system.
Although an individual's serum 25 OH D concentration is the best biochemical marker of vitamin D status, functional indicators of bone length and reduced bone mass rickets in the extreme form serve as useful evaluative outcomes of deficiency. Vitamin D intakes between 8. A recent study in Chinese infants Specker et al.Calcium, Phosphorus & Vitamin D - Kate Wesseling, MD - Pediatric Grand Rounds
Seasonal variation in vitamin D status of infants is also apparent. In studies from the United States Greer et al. Calcium in blood and extracellular fluid: Roughly half of the calcium in blood is bound to proteins. The concentration of ionized calcium in this compartment is normally almost invariant at approximately 1 mM, or 10, times the basal concentration of free calcium within cells. Also, the concentration of phosphorus in blood is essentially identical to that of calcium.
A vast majority of body calcium is in bone.
The remainder of body phosphate is present in a variety of inorganic and organic compounds distributed within both intracellular and extracellular compartments. Normal blood concentrations of phosphate are very similar to calcium. Fluxes of Calcium and Phosphate Maintaining constant concentrations of calcium in blood requires frequent adjustments, which can be described as fluxes of calcium between blood and other body compartments. Three organs participate in supplying calcium to blood and removing it from blood when necessary: The small intestine is the site where dietary calcium is absorbed.
Importantly, efficient absorption of calcium in the small intestine is dependent on expression of a calcium-binding protein in epithelial cells. Bone serves as a vast reservoir of calcium. Stimulating net resorption of bone mineral releases calcium and phosphate into blood, and suppressing this effect allows calcium to be deposited in bone. The kidney is critcally important in calcium homeostasis.
Under normal blood calcium concentrations, almost all of the calcium that enters glomerular filtrate is reabsorbed from the tubular system back into blood, which preserves blood calcium levels. If tubular reabsorption of calcium decreases, calcium is lost by excretion into urine. Hormonal Control Systems Maintaining normal blood calcium and phosphorus concentrations is managed through the concerted action of three hormones that control fluxes of calcium in and out of blood and extracellular fluid: Parathyroid hormone serves to increase blood concentrations of calcium.
Mechanistically, parathyroid hormone preserves blood calcium by several major effects: Stimulates production of the biologically-active form of vitamin D within the kidney.
Facilitates mobilization of calcium and phosphate from bone. To prevent detrimental increases in phosphate, parathyroid hormone also has a potent effect on the kidney to eliminate phosphate phosphaturic effect. Maximizes tubular reabsorption of calcium within the kidney.