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Biomedical subjects

R Schenk

Publications and source records attributed to R Schenk.

At least 55 records · Page 3Linked to original sources

Relation between bone mineralization, Ca absorption, and plasma Ca in phosphonate-treated rats.

Disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) is known to inhibit the crystallization of calcium phosphate salts in vitro. Large doses of EHDP administered in vivo inhibit skeletal mineralization, decrease intestinal calcium absorption, and produce hypercalcemia. In the present study, EHDP or one of 13 other phosphonates were given to rats at 10 mg P/kg-day sc for 7 days in order to better define the nature of the relationship between bone mineralization, intestinal absorption, and plasma calcium in the regulation of calcium homeostasis. Each of the phosphonates which inhibited skeletal mineralization in vivo also inhibited crystallization in vitro, but the converse was not true. A very close correlation was found between inhibition of skeletal mineralization, decreased intestinal calcium absorption, and slight hypercalcemia. A dose-response study with two compounds also revealed the same close correlation. It is argued that the impairment of intestinal calcium absorption in phosphonate-treated rats may represent a secondary homeostatic response to the primary effect of the drugs on bone mineralization. This response may be mediated by an elevation of a fraction of plasma calcium.

Animals↗

[Treatment of 10 cases of symptomatic Paget's disease with etidronate (EHDP)].

10 patients with active symptomatic Paget's disease of bone have been treated for 6 months with disodium etidronate (EHDP) at a dose of 20 mg/kg/day. A statistically significant fall in the serum levels of alkaline phosphatase and urinary hydroxyproline was observed. However, only 2 patients experienced a significant reduction of bone pain. 6 patients were partially improved and 2 patients showed no change. Iliac crest biopsies after treatment demonstrated dimunution of the abnormal structure of the pagetic bone, but also a considerable increase in unmineralized osteoid borders. The future potentialities for treatment of Paget's disease are discussed.

Aged↗

The comparative effects of vitamin d deficiency and ethane-1-hydroxy-1,1-diphosphonate administration on the histology and glycolysis of chick epiphyseal and articular cartilage.

A comparison has been made between the effect of a vitamin D--deficient diet and treatment with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) on the morphology of chick epiphyseal cartilage and on the production of lactate in vitro by epiphyseal and articular cartilage. The cell populations in the growth plate were different following the two treatments. Vitamin D deficiency was characterized by an increase in proliferating cells, with a relative paucity of hypertrophic cells; EHDP treatment was characterized by an increase in hypertrophic cells. When similar cell types were compared, neither treatment changed lactate production from the control value. This stresses the need to correlate the morphology of cell types with their metabolic function. The present results indicate that the major effect of vitamin D deficiency in the chick is to block the differentiation of proliferating to hypertrophic cells. In contrast, EHDP may act by inhibiting calcification directly. Even though EHDP at the doses used is known to interfere with the production of 1,25-dihydroxycholecalciferol there is no block to cell differentiation under EHDP similar to that seen in dietary deficiency of vitamin D.

Animals↗

[Treatment of Paget's disease with phosphonates].

A group of 22 patients with Paget's disease of bone was treated with a diphosphonate (sodium etidronate; EHDP), a stable synthetic analogue of inorganic pyrophosphate. This substance was given during 3 months at the dose of 20 mg/kg body weight per day, and proved effective by reducing the raised urinary excretion of total hydroxyproline and by lowering the concentration of serum alcaline phosphatase. It also improved the disease-related osteo-articular pain in 60% of the patients. A rise in serum phosphate under EHDP therapy is due to the increase in renal tubular reabsorption of phosphate. Bone histology showed regression of disease activity and the appearance of lamellar structure in newly formed bone. Because of a transient increase of the amount of uncalcified osteoid, it is advisable to give the diphosphonate in courses not over 3 months or at a reduced daily dose.

Adult↗

Action of 1,25-dihydroxyvitamin D3 and a diphosphonate on calcium metabolism in rats.

The effect of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) on Ca balance, 45Ca kinetics, and bone morphology has been studied in control rats and rats given disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP), 10 mg P/kg sc per day. This large dose of EHDP is known to inhibit bone mineralization and intestinal calcium absorption and to depress the endogenous production of 1,25-(OH)2D3. In conctrol rats, 1,25-(OH)2D3 increased intestinal calcium absorption. However, in contrast to the enhanced calcium absorption that results from an augmentation of dietary calcium, the 1,25(OH)2D3-induced augmentation of calcium absorption does not lead to a rise in calcium retention, the intestinal effect being matched by an increased excretion of urinary calcium. The EHDP-induced decrease of intestinal calcium absorption could be completely prevented by the concomitant administration of 1,25-(OH)2D3 but not the inhibition of bone mineralization. Therefore, in contrast to the impairment of calcium absorption, that of bone mineralization brought about by large doses of EHDP cannot be merely attributed to a decreased production of 1,25-(OH)2D3.

Animals↗