1. It has been suggested that a dominant mutation in the mouse is a suitable model for the most frequent form of human vitamin D-resistant rickets, X-linked hypophosphataemia. The mutant mice have reduced tubular reabsorption of phosphate, hypophosphataemia, rachitic bone lesions, moderate dwarfism and mild hypocalcaemia. 2. The present work shows that male hypophosphataemic (HYP/Y) mice have a decrease in the tubular capacity to reabsorb calcium as compared with normal littermates (+/Y). This decrease appears to be related to the phosphate status of the animals, since it is much more pronounced when the animals are fed on a low phosphorus diet. 3. The decrement in the tubular reabsorption and plasma concentration of calcium in HYP/Y mice is not accompanied by an augmentation in the absolute urinary excretion of calcium. It is associated with an increase in the urinary excretion of cyclic AMP. Furthermore, removal of the thyroparathyroid glands leads to much larger fall in the plasma concentration of calcium in HYP/Y than in +/Y mice. 4. Thus HYP/Y mice, when compared with normal littermates, have decreased tubular reabsorption of calcium with no apparent increase in the mobilization of calcium from intestinal and body sources as reflected by the absence of an augmentation in the absolute amount of calcium excreted in the urine. These findings could account for a propensity to hypocalcaemia which would be partially compensated by secondary hyperparathyroidism. This could explain the increase in urinary cyclic AMP excretion and the exaggerated hypocalcaemic response to removal of the parathyroid glands observed in murine X-linked hypophosphataemia.

1. The effect of long-term administration of parathyroid hormone (PTH) on whole-body calcium and ash weight of individual bones has been studied in normal and osteoporotic adult female rats in order to examine whether such a treatment could induce a positive calcium balance. 2. Osteoporosis was induced by calcium restriction during pregnancy and lactation. Sequential measurements of whole-body calcium were made by neutron activation. 3. In non-osteoporotic intact and thyroparathyroidectomized rats a daily dose of 75 units of human PTH 1–34 given subcutaneously for 3 weeks increased whole-body calcium. 4. In osteoporotic animals 25–50 units of either bovine PTH 1–84 or human PTH 1–34 given subcutaneously twice daily for 6 weeks increased both whole-body calcium and ash weight of individual bones. Microradiographic examination of the tibiae indicates, however, that PTH administration does not result in the restoration of individual trabeculae lost during the development of osteoporosis. 5. The results show that PTH can enhance skeletal mass in both normal and osteoporotic rats. In osteoporotic animals the restoration of whole-body calcium and ash weight of individual bones is not accompanied by a return of the morphological structure of the tibia to normal.

1. Protein-binding assays have been used to measure plasma 1,25-dihydroxy-vitamin D [1,25-(OH) 2 D] as well as 25-hydroxy-vitamin D [25-(OH)D] in rats given 10 mg of phosphorus (P) day −1 kg −1 as ethane-1-hydroxy-1,1-diphosphonate (EHDP). 2. In control animals given a normal laboratory chow plasma 25-(OH)D and 1,25-(OH) 2 D were about 40 nmol/l and 300 pmol/l respectively. 3. EHDP produced a decrease of plasma 1,25-(OH) 2 D to below 50 pmol/l in 2 days. 4. Both in control and in EHDP-treated rats plasma 1,25-(OH) 2 D increased when dietary calcium (Ca) was restricted to 0.1%, or dietary P to 0.2%, indicating that the well-known stimulatory effect of Ca or P deprivation was at least partially effective in EHDP-treated rats. 5. In response to an increase of the oral supply of vitamin D 3 to 65 nmol/day the plasma level of 25-(OH)D rose in both control and EHDP groups. Plasma 1,25-(OH) 2 D was not increased above the normal value in control rats. In EHDP-treated rats, however, plasma 1,25-(OH) 2 D rose to a level equal to that in controls, suggesting that the effect of EHDP on plasma 1,25-(OH) 2 D can be overcome at high precursor concentration.

1. Previous studies have shown that in thyroparathyroidectomized rats injection of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at doses that inhibit bone mineral retention (0.16 mmol = 10 mg of phosphorus/kg body wt. per day subcutaneously) leads to a decrease in the net tubular reabsorption of phosphate. 2. In the present work the tubular response to EHDP (0.16 mmol/kg body wt.) injected subcutaneously for 9 days has been localized by free-flow micropuncture in thyroparathyroidectomized rats. 3. The results show that the net tubular reabsorption of phosphate along the first portion of the (early) proximal tubule was markedly depressed in the EHDP-injected thyroparathyroidectomized rats compared with that in the pair-fed thyroparathyroidectomized control animals. In this latter group the delivery of phosphate to the distal tubule was larger than in the final urine, confirming previous reports. In the EHDP-injected thyroparathyroidectomized rats no difference in delivery of phosphate was found between the distal tubule and the final urine, suggesting that diphosphonate inhibited net reabsorption of phosphate in the terminal nephron. 4. The sites of the EHDP-induced changes in the tubular handling of phosphate were similar to those previously determined for the adaptive response to an increase in the supply of phosphate.

1. Chronic administration of 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] can normalize plasma calcium in human hypoparathyroidism and in thyroparathyroidectomized animals. The effect of 1,25(OH) 2 D 3 on plasma calcium is associated with an increase in urinary calcium excretion. In an attempt to prevent this increase, thyroparathyroidectomized rats receiving 1,25(OH) 2 D 3 were also treated with hydrochlorothiazide for 9–11 days. 2. Calcium clearance studies show that hydrochlorothiazide stimulated the tubular reabsorption of calcium in thyroparathyroidectomized rats treated with 1,25(OH) 2 D 3 . 3. Calcium balance and kinetic studies indicated that hydrochlorothiazide decreased 1,25(OH) 2 D 3 -induced hypercalciuria in thyroparathyroidectomized rats. Hydrochlorothiazide did not affect the 1,25(OH) 2 D 3 -induced increase in plasma calcium. The hypocalciuric effect of hydrochlorothiazide was not associated with significant changes in calcium deposition into or release from bone. 4. In thyroparathyroidectomized rats treated with 1,25(OH) 2 D 3 the hypocalciuric effect of hydrochlorothiazide was associated with a fall in intestinal calcium absorption. Overall, the calcium balance was unaffected. 5. Thus it appears that hydrochlorothiazide reduces the 1,25(OH) 2 D 3 -induced hypercalciuria in parathyroid hormone-deficient animals by decreasing intestinal calcium absorption. Despite the decreased absorption, hydrochlorothiazide does not reduce the 1,25(OH) 2 D 3 -induced increase in plasma calcium.

1. The existence of tubular secretion of inorganic phosphate (P i ) in the mammalian kidney has been investigated by studying the renal response of rats infused with sodium phosphate by three different techniques. 2. Clearance studies indicate that, in anaesthetized rats, the net tubular reabsorption decreases markedly in response to P i infusion. In conscious rats, the clearance of P i slightly exceeded that of inulin at high plasma P i concentration. 3. Free-flow micropuncture in control rats showed a net tubular reabsorption of P i along the proximal tubule, and probably between the end of the distal tubule and the ureteral urine. In phosphate-loaded rats, whether receiving parathyroid hormone or not, an apparent net secretion of P i was observed between the end of the distal tubule and the ureteral urine. In the phosphate-loaded group receiving parathyroid hormone, net secretion was also observed very early in the proximal tubule followed by a predominant reabsorption along this segment. Thus the early proximal tubule and probably also the terminal nephron can be the site of either net reabsorption or net secretion. 4. Microperfusions of proximal tubules show a fall in the specific radioactivity of the perfused radioactive P i solution, indicating entry of P i into the lumen.

1. Ligated intestinal segments from rats treated with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at the daily dose of 16 μmol (1 mg of phosphorus)/kg subcutaneously for 7 days show an increased rate of calcium absorption. 2. This dose of EHDP enhances the intestinal accumulation of a vitamin D 3 metabolite with the chromatographic characteristics of 1,25-dihydroxycholecalciferol.