Clayton Rich

Formation, mineralization, and resorption of bone in vitamin D-deficient rats.

Quantitative histologic methods have been devised to measure several processes dealing with formation and mineralization of matrix and bone resorption. In vitamin D-deficient rats, the total osteoblastic matrix formation rate was 20% less and the total osteoclastic bone resorption rate was 80% more than in pair-fed control rats. These changes were found to be primarily because of changes in the rates of matrix formation and of bone resorption per unit area of forming or resorbing surfaces rather than to changes in the areas of these surfaces. The rate of maturation of osteoid and the rate of initial mineralization both were reduced to half of normal in the vitamin D-deficient rats. These variables related to matrix formation and mineralization were significantly correlated with the concentration of calcium but not with the concentration of phosphate in serum. The occurrence of hypocalcemia is interpreted as the consequence, both of reduced calcium absorption and of inadequate resorptive response of bone cells to homeostatic stimuli, such that, although bone resorption was greater than normal, it did not adequately compensate for the reduced intestinal absorption.

Deposition in and release of vitamin D3 from body fat: evidence for a storage site in the rat

Vitamin D in all body tissues was radio-labeled by supplementing completely vitamin D-deficient weanling rats with oral vitamin D(3)-4-(14)C for 2 wk. All vitamin D was then withheld, and radioactivity and vitamin D content in a variety of organs and tissues were measured. Adipose tissue was found to contain by far the greatest quantity of radioactivity throughout the 3 month experimental period. Immediately after supplementation, half of the total radioactivity in adipose tissue corresponded to unaltered vitamin D(3), and the other half to polar metabolites and esters of vitamin D(3) and unidentified peak II. 1 month later there was approximately the same proportion but a decrease in the total quantity of each form. We conclude that adipose tissue is the major storage site for vitamin D(3) in its several forms. Unaltered vitamin D(3) was the principal storage form observed and presumably a source available for conversion to other metabolites during deprivation.

The Absorption of Calcium Carbonate

Excerpt Although calcium carbonate (CaCO3) is widely used in the treatment of peptic ulcer disease and is freely available on the open market, relatively little information about its absorption is ...

Absorption of calcium measured by intubation and perfusion of the intact human small intestine

Absorption of calcium was measured by direct intubation and perfusion of the small intestine in 10 volunteer normal adult subjects, two adults with celiac-sprue, and one with a parathyroid adenoma. A total of 60 studies were completed using one of two different levels, duodenojejunum or ileum. Solutions containing stable calcium, radiocalcium(47), and a nonabsorbable dilution-concentration marker, polyethylene glycol, were infused at a uniform rate via the proximal lumen of a triple-lumen polyvinyl tube. The mixed intraluminal contents were continuously sampled by siphonage from two distal sites, 10 and 60 cm below the point of infusion. Unidirectional flux rates, lumen to blood and blood to lumen, and net absorption of calcium for the 50 cm segment of small intestine between the two collection sites were calculated from the measured changes in concentration of stable calcium, calcium-47, and polyethylene glycol.Flux of calcium from lumen to blood in the duodenojejunum of normal subjects was appreciable even when the concentration of calcium in the perfusate was below that of extracellular fluid and, as the intraluminal concentration of calcium was increased through a range of 0.5-3.5 mumoles/ml, was positively correlated, ranging from 1.9 to 7.0 mumoles/min per 50 cm. Repeated studies of individual subjects demonstrated a consistent pattern of absorptive efficiency in each, but significant variability from person to person. Flux from lumen to blood in the ileal segment occurred at a much lower rate than that found in the proximal intestine, and there was not a significant dependence upon intraluminal calcium concentration. The opposite flux, from blood to lumen, was low both in the duodenojejunum and ileum (average 0.76 mumoles/min per 50 cm) and was independent of the intraluminal calcium concentration. Unidirectional flux, lumen to blood, from the duodenojejunum was not altered by parathyroid extract administered at the time of the infusion, but was accelerated in the subject with a parathyroid adenoma and markedly reduced in the two subjects with celiac-sprue.

Inhibition of Bone Matrix Formation, Mineralization, and Resorption in Thyroparathyroidectomized Rats

In previous work we found that vitamin D-deficient and also calcium-deficient rats developed hypocalcemia and an impairment of bone formation and mineralization. The present study of thyroparathyroidectomized (TPTX) rats was undertaken to determine the effect of hypocalcemia without secondary hyperparathyroidism. TPTX rats fed a normal diet developed hypocalcemia and hyperphosphatemia in association with impairment of osteoblastic bone matrix formation and of mineralization of newly formed matrix. The serum calcium x phosphorus product was not decreased. The decreased formation was largely due to a reduction in matrix apposition indicating decreased synthetic activity of individual ostcoblasts. In contrast to the above results, when TPTX rats were fed a high-calcium diet to prevent hypocalcemia, no impairment of either formation or mineralization was found. From the results of these two experiments, it is reasonably certain that hypocalcemia was responsible for the inhibition of formation and mineralization. Moreover, based on the magnitude of the changes in serum calcium and bone parameters in TPTX rats, hypocalcemia could have accounted for the inhibition of formation and mineralization in calcium-deficient as well as vitamin D-deficient rats. In TPTX rats the mineralization defect was manifested by decreases in both the rate of osteoid maturation (indicating a delayed onset of mineralization) and the rate of mineralization. A strong correlation (r = 0.95, P < 0.001) was observed between these two rates suggesting a tight coupling of these two aspects of mineralization.TPTX rats also had lower bone resorption rates and higher serum phosphorus levels than sham-operated animals when the normal calcium diet was fed but not when the high-calcium diet was fed. Thus the inhibition of bone resorption in TPTX rats was at least partially prevented by correction of hyperphosphatemia. This is consistent with previous work showing an inverse relationship between serum phosphorus and bone resorption. Accordingly, the depression of bone resorption in TPTX rats was probably due to hyperphosphatemia as well as to hypoparathyroidism.

Studies of intestinal absorption of calcium45 in man

Gastrointestinal absorption of calcium has been studied in 37 tests of 30 fasted subjects. One radioisotope of calcium, Ca45, was given orally and another, Ca47, was given intravenously, so that the true absorption could be calculated from the amount of these isotopes appearing in the stools. Completeness of collection was determined by use of Cr51-labeled erythrocytes as an unabsorbed marker. Normal subjects absorbed 15 to 59 per cent of the dose. Patients with the clinical diagnosis of milk-alkali syndrome and a control group of patients with different diseases but with normal calcium metabolism and gastrointestinal function were within the normal range. Subjects with osteomalacia absorbed less and several hypercalcemic pateints, including 3 hyperparathyroid subjects, absorbed more than the normal amount.

Response to Sodium Fluoride in Severe Primary Osteoporosis

Excerpt It has been shown from epidemiological studies that a moderate intake of fluoride will eventually cause osteosclerosis that is not associated with significant morbidity except in the most e...

Measurement of Bone Mass from Ultrasonic Transmission Time.

Summary When a beam of pulsed sound is passed between two transducers a fixed distance apart, the transit time depends upon the velocity of sound in the medium separating them. Because the velocities of sound in soft tissues are similar and much less than in bone, an instrument which records changes in transmission time can be used to determine the mass of bone present in an intact limb. When measurements were made on samples of cortical bone and of the humerus of a rabbit (either intact or stripped of the soft tissues) there was good agreement between the predicted and subsequently chemically determined mass of calcium present.

Dialysis Bone Disease

15 patients on chronic hemodialysis were investigated by means of quantitative bone histology. Bone changes were found regularly in the absence of clinical signs. They were not qualitatively different

Bone resorption without parathyroid hormone: influence of a low phosphorus diet.

SummaryThe effect of a low phosphorus diet on bone resorption is studied in thyroparathyroidectomized rats. Bone resorption is estimated from the marrow cavity area of a cross-section of the tibia. The rate of calcium mobilisation from bone is estimated by serum specific activity of45Ca/40Ca after labelling of the diet. Bone resorption is increased by feeding a low phosphorus diet, suggesting a direct effect of hypophosphatemia stimulating bone resorption, independent of any action of parathyroid hormone.