Role of 1,25-Dihydroxyvitamin D ₃ in Maintaining Serum Phosphorus and Curing Rickets

Abstract

The intravenous injection of a single dose of 650 pmote of 1,25-dihydroxyvitamin D3 to rats fed a vitamin D-deticient, low-phosphorus diet caused an elevation of serum phosphorus within 5 hours which reached a maximum in about 10-12 hours. This elevated serum phosphorus returned to deficiency levels 2-3 days later. On the other hand, a single injection of 650 pmoles of 25-hydroxyvitamin D3 produced a significant rise at 12hours, reached a maximum in 24-36 hours, and was maintained for at least 7 days. before it can function (1). It generally has been assumed that this function involves (a) the stimulation of calcium absorption, and (b) the stimulation of calcium mobilization from bone, which in turn elevates serum calcium and phosphate levels. The elevation of these ions in the extracellular fluid is believed responsible for the well-known effect of vitamin D in the mineralization of bone (2-4). However, there are facts that are incompatible with such a simple explanation. Rickets in rats can be produced only with a diet deficient in both vitamin D and phosphorus (5), and is associated with low serum phosphorus and normal to slightly elevated serum calcium concentrations (5, 6). Although vitamin D-deficient rats fed low-phosphorus diets absorb adequate calcium to mineralize their bone (7), phosphorus is limiting. The development of rickets in man is in three phases, two of which are associated with a low serum phosphorus concentration (8).The present report shows that 1,25-(OH)2D3 dramatically and rapidly increases the concentration of phosphorus in the serum of rats on a low-phosphorus diet, and that this increase is independent of the well-known increases in intestinal calcium transport and bone calcium mobilization and may result from a specific effect of 1,25-(OH)2D3 in stimulating phosphate reabsorption in the kidney and possibly in stimulating phosphate absorption from the intestine. Additionally, evidence is offered that the mineralization of bone in rachitic rats is a response to increased levels of serum phosphorus induced by vitamin D3.MATERIALS AND METHODS Animals. Weanling male rats purchased from the Holtzman Co., Madison, Wis., were maintained in overhanging wire cages and fed a vitamin D-deflcient diet that contained either 1.2% calcium-0.1% phosphorus and 18% casein + 0.2% cystine (9), or 0.47% calcium-0.016% phosphorus and 18% egg white instead of casein (5). After the animals had been fed one of these diets for two weeks, they developed severe rickets, as evident in AgNO3-stained sections of radii and ulnae (10).

Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23 concentrations and the urinary excretion of calcium

“…Calcium and P absorption in the intestine and Ca and P reabsorption in the kidney regulate overall mineral balance (18)(19)(20)(21)(22)(23). Active Ca and P absorption in the intestine are regulated by the vitamin D metabolite, 1α,25(OH) 2 D (20,24,25).…”

CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D production in vivo

“…The normal serum concentration of 1,25(OH) 2 D 3 in Cyp2r1 −/− and Cyp2r1 −/− / Cyp27a1 −/− mice was further supported by the fact that the mice did not develop rickets in response to a rachitogenic high-calcium and low-phosphorus diet. At 4-6 wk of age, mice were switched to a purified diet containing 1.2% Ca/0.02% P. The 1.2% Ca/0.02% P diet is expected to produce rickets in the absence of vitamin D (28). The serum calcium level of the mice on the diet steadily increased, whereas the phosphorus level quickly dropped, rendering the mice hypophosphatemic (Fig.…”

A cell-autonomous requirement for neutral sphingomyelinase 2 in bone mineralization

“…In humans, genetic mutations may lead to a variety of diseases affecting ECM mineralization in skeletal and dental tissues, which include X-linked hypophosphatemia, hypophosphatasia, rickets, and some forms of osteogenesis/dentinogenesis imperfecta (Tanaka and Deluca, 1974;Whyte, 1994;Nesbitt et al, 1999;Glorieux et al, 2002;Goldberg et al, 2008). Although considered as a critical physiological process, the molecular mechanism of ECM mineralization is still not fully understood.…”