In vitro effects of aluminum on bone phosphatases: a possible interaction with bPTH and vitamin D3 metabolites.
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Acid Phosphatase↗
Biomedical subjects
S Balsan
Publications and source records attributed to S Balsan.
Possible link between changes in plasma 24,25-dihydroxyvitamin D and healing of bone resorption in dialysis osteodystrophy.
Histomorphometric studies of bone biopsies were performed on 12 hemodialyzed patients before and after six months of treatment with 25-(OH) and 1 alpha-(OH) vitamin D3. Patients could be classified into three groups according to bone resorption: Group I with normal bone resorption; Group II with elevated initial bone resorption unresponsive to vitamin D treatment; group III with elevated initial bone resorption sensitive to vitamin D treatment. None of the patients had histological signs of osteomalacia. In Group I, plasma concentrations of 24,25-(OH)2D and the ratio of 24,25-(OH)2D to 25-(OH) D remained in the normal range throughout the study; in Group II these parameters were subnormal initially and did not increase above normal except in one case; in Group III, plasma concentrations of 24,25-(OH)2D were high before or at the beginning of vitamin D administration and normal at the time of the second biopsy and wide variations were observed in the ratio of 24,25-(OH)2D to 25-(OH)D. No difference was found between these last two groups with regard to the cumulative dose of vitamin D derivatives administered or the changes in plasma PTH, CT, calcium and phosphate. These observations suggest a specific regulation of plasma 24,25-(OH)2D concentrations in hemodialyzed patients and a possible link (independent of circulating PTH, CT, or phosphate) between this regulation and healing of bone resorption. However, no correlation was found between plasma 24,25-(OH)2D and either one of the simultaneously measured biochemical or histological parameters.
24,25-Dihydroxyvitamin D 3↗
In vitro action of 1,25-dihydroxycholecalciferol and 24,25-dihydroxycholecalciferol on matrix organization and mineral distribution in rabbit growth plate.
Growth plates of 18-day-old rabbits were incubated in a protein-free synthetic medium, either without any additive, with 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] (10(-10) M), with 24,25-dihydroxycholecalciferol [24,25-(OH)2D3] (10(-10) M and 10(-9) M), with both metabolites, or with the ethanol solvent alone. Cartilages, before and after 5 days of incubation, were studied by light and electron microscopy. The intracellular calcium distribution was analyzed by the potassium pyroantimonate method, and the calcium content was verified by x-ray microprobe analysis. When compared to nonincubated samples the cartilages incubated for 5 days without any additive as well as the cartilages incubated with the solvent alone showed excessive hydratation and hypertrophy of the chondrocytes, which had lost their columnar arrangement. The matrix and the cells were devoid of mineral. The ultrastructure of the cells was well preserved. These changes were largely prevented by the presence of both vitamin D3 metabolites. With regard to calcium distribution, 1,25-(OH)2D3 maintained calcium in mitochondria and crystals in matrix vesicles, whereas 24,25-(OH)2D3 only partly maintained mitochondrial mineral. In the chondrocytes incubated with this latter metabolite, small calcium granules were seen in the cytoplasm; most vesicles were devoid of crystals, and amorphous precipitates were seen in the matrix. These data demonstrate the in vitro influence of vitamin D3 metabolites on the organization and mineralization of the cartilage matrix and on the distribution of intracellular calcium in chondrocytes. Furthermore, they support the hypothesis that the in vitro action of 1,25-(OH)2D3 is different from that of 24,25-(OH)2D3 in that 1,25-(OH)2D3 may influence calcium storage in mitochondria and matrix vesicles, whereas 24,25-(OH)2D3 is likely to be involved in calcium transport and release.
24,25-Dihydroxyvitamin D 3↗
Vitamin D nutrition increases skin tyrosinase response to exposure to ultraviolet radiation.
The influence of vitamin D nutrition on melanogenesis in skin induced by UV radiation was studied in pigmented adult rats. Melanogenesis, assessed by the activity of skin tyrosinase (radiometric assay), was studied in vitamin-D-deficient and vitamin-D-fed rats exposed to UV (0.1 J/cm2, 290-320 nm). The tyrosinase activity in skin was not significantly changed by vitamin D treatment alone. In contrast, the induction of tyrosinase activity provoked by UV radiation was greater in vitamin-D-fed than in vitamin-D-deficient rats. The increase in skin tyrosinase activity in response to UV was preceded by an increase in skin cAMP levels. This rise in cAMP was greater in vitamin-D-treated rats than in vitamin-D-deficient rats. The pretreatment of rats with phosphodiesterase inhibitor potentiated the effect of vitamin D on skin tyrosinase activity. The low serum calcium levels in the vitamin-D-deficient group were evidently not responsible for the lower UV induction of skin tyrosinase activity because the vitamin-D-deficient rats with normal serum calcium levels (supplemented with 20% lactose and 2% calcium in the diet) were also unable to show maximal induction of skin tyrosinase activity in response to UV radiation requires the presence of adequate vitamin D. cAMP may be involved in the mediation of this effect. The relationship observed between the vitamin D status of animals and tyrosinase activity of skin could provide an effective feed-back control for protection against UV and vitamin D intoxication.
1-Methyl-3-isobutylxanthine↗
In vitro formation of 25-hydroxyvitamin D3 metabolites in endometrium: dependence on the hormonal status of the rat.
Rat myometrial tissue and endometrial cells were incubated with labeled 25-hydroxyvitamin D3 ([3H-26,27] 25OHD3) for 70 min at 37 C, and the resulting metabolites were isolated by sequential Sephadex LH-20 chromatography and high performance liquid chromatography. Two peaks more polar than 25OHD3 were present on the Sephadex LH-20 chromatograms. One of these metabolites had an identical chromatographic behavior on three different HPLC systems and an identical sensitivity to periodate cleavage as biosynthetic [3H-26,27] 24,25-dihydroxyvitamin D3 ([3H-26,27]24,25-(OH)2D3]. The in vitro production of this putative 24,25-(OH)2D3 was significantly higher in castrated animals than in normal adult rats. Treatment of rats with 17 beta-estradiol and/or medroxyprogesterone acetate reversed the effect of ovariectomy on 25OHD3 conversion. The in vitro production of the putative 24,25-(OH)2D3 was low during the estrous cycle and the initial stage of pregnancy. A dramatic increase in its production was observed on days 12 and 14 of pregnancy. 25OHD3 conversion was higher in endometrium than in myometrium under every experimental condition tested. These results demonstrate the ability of rat uterine tissue to convert 25OHD3 into more polar derivatives in vitro, and show the influence of the hormonal status of the rat on this in vitro capacity.
24,25-Dihydroxyvitamin D 3↗
[Osteomalacia as a result of aluminum poisoning during chronic hemodialysis].
The iliac crest biopsy of an uremic child, suffering from nephronophtisis, and hemodialyzed since the age of 11 1/2 years, was examined by histomorphometry, electron-probe X-ray microanalysis and ion microscopy. The results have been compared with those obtained with the same techniques in the bone tissue of 11 hemodialyzed aluminum-intoxicated adults. In this child, radiology of the skeleton and plasma biochemistry suggested secondary hyperparathyroidism; by contrast, histology showed impaired mineralization, little bone resorption, and aluminum deposits at the limit between osteoid and calcified tissue similar to those observed in the bone tissue of the adults. This observation, and the fact that the child had a high plasma aluminum level, and that dialysis was performed with softened aluminum-rich water, strongly suggests that the severe osteomalacia of this child was due to aluminum toxicity.
Adolescent↗
Aluminum localization in bone from hemodialyzed patients: relationship to matrix mineralization.
It has been suggested that in uremic bone, aluminum interferes with normal mineralization. Aluminum content and aluminum localization were studied in iliac crest biopsies of two groups of patients on regular hemodialysis; one group had histologic osteomalacia, and little or no bone resorption (group 1); the other, osteitis fibrosa and no mineralization defect (group 2). Group 1 patients had significantly higher plasma aluminum concentrations than those of group 2. No difference was found in bone aluminum content, which was above normal in both groups. In the bone samples of the osteomalacic subjects, aluminum was mainly localized at the limit between osteoid and calcified tissue, the site where the bone mineral is normally first deposited. Osteomalacia could not be related to hypocalcemia or to phosphate depletion. Active vitamin D derivatives (25-hydroxycholecalciferol and 1alpha-hydroxycholecalciferol) failed to prevent or to improve the bone disease. In the bone samples of group 2 subjects, aluminum could not be localized by the methods used, except in the two cases with greatly elevated bone aluminum, where it was mainly localized on cement lines. In group 2 subjects, immunoreactive parathyroid hormone plasma concentration, osteoclast surface, and marrow fibrosis were significantly higher than they were in group 1 subjects. It is concluded that in bone from uremic patients on regular dialysis, aluminum can induce a particular form of osteomalacia, resistant to the vitamin D active derivatives. The bone disease is only observed in the absence of severe secondary hyperparathyroidism. This suggests that parathyroid hormone may be involved in the development of the aluminum-induced mineralization defect.
Adult↗
Changes in plasma 1,25 and 24,25-dihydroxyvitamin D after renal transplantation in children.
The purpose of this investigation is to analyze changes in plasma 1,25-(OH)2D and 24,25-(OH)2D after successful renal transplantation in 20 children and young adults. Studies were performed on 8 subjects between the 1st and 10th month and on 12 others between the 20th and 30th to 36th month. Samples were assayed for plasma and urinary calcium, inorganic phosphate, creatinine, plasma bicarbonate, immunoreactive parathyroid hormone, 25-(OH)D, 24,25-(OH)2D, and 1,25-(OH)2D concentrations. Results showed the following: (1) All subjects had normal or high plasma levels of dihydroxyvitamin D metabolites. (2) In subjects with normal GFR's there was a significant inverse correlation between plasma 1,25-(OH)2D concentrations and tubular reabsorption of phosphorus. (3) These correlations were not found in subjects with subnormal creatinine clearances (50 to 100 ml/min/1.73 m2) even though plasma 1,25-(OH)2D concentrations in these subjects were similar to those with normal creatinine clearances. (4) In subjects with subnormal creatinine clearances, an increase in plasma 1,25-(OH)2D concentrations to very high levels was observed during the first months following renal transplantation.
24,25-Dihydroxyvitamin D 3↗
Skin calcium binding protein is localized in the cytoplasm of the basal layer of the epidermis.
Using a serum raised in rabbits against a calcium binding protein extracted from rat skin, the cutaneous localization of this protein was studied by indirect immunofluorescence. The skin calcium binding immunoreactivity was found in the epidermis but not in the dermis; it was localized in the cytoplasm of the basal cell layer of both skin and malpighian mucosa. There was not species specificity; this allowed the tracing of the protein in human epidermis as well where it was also expressed only in the basal cells. This is the first demonstration of the unique localization of a specific protein within the cytoplasm of the basal cell layer of the epidermis. This localization may help to elucidate the physiological role of this protein.
Animals↗
Suppressive effects of 24,25-dihydroxycholecalciferol on bone resorption induced by acute bilateral nephrectomy in rats.
The possible suppressive effects of 24,25-dihydroxycholecalciferol on secondary hyperparathyroidism and increased bone resorption were investigated in adult rats raised on a diet normal in calcium, phosphorus, and vitamin D, and subjected to acute bilateral nephrectomy. The animals had received subcutaneous radiocalcium 4 wk before the experiment. 5 h after nephrectomy an increase in serum total calcium, (45)Ca-specific activity, citrate, phosphorus, and magnesium concentrations were observed. Serum immunoreactive parathyroid hormone increased, while serum calcitonin decreased. The osteoclast count in the tibial metaphyses was augmented. The biochemical and histological changes observed were partly parathyroid hormone and calcitonin independent, as they also occurred in parathyroidectomized hypocalcemic rats. Pretreatment with 650 pmol of 24,25-dihydroxycholecalciferol 16 h before nephrectomy prevented bone calcium mobilization and diminished the rise in serum total calcium and citrate both in parathyroid-intact and in parathyroidectomized animals. In parathyroid-intact rats, serum immunoreactive parathyroid hormone and calcitonin remained normal in spite of the fall in serum-ionized calcium, and the number of osteoclasts did not increase. In parathyroidectomized rats, 24,25-dihydroxycholecalciferol did not prevent the postnephrectomy rise in the osteoclast count. This latter observation suggests that this metabolite exerts its effect on bone either by acting on cells other than osteoclasts, i.e., the osteocytes, or by inhibiting cell activity. At equimolar dosage 1,25-dihydroxycholecalciferol had a potent stimulatory effect on bone resorption. This effect of 1,25-dihydroxycholecalciferol was partly blocked by the simultaneous administration of 24,25-dihydroxycholecalciferol. The potential clinical significance of these observations remains to be determined.
24,25-Dihydroxyvitamin D 3↗
Somatostatin and vitamin D3 metabolites in rat calvarium: in vitro evidence for physiological interaction.
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Animals↗
Evaluation of 25(OH)D loss in dialysate of children on continuous ambulatory peritoneal dialysis.
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25-Hydroxyvitamin D 2↗
[Measurements of plasma concentrations of active vitamin D metabolites in children: interest and limit (author's transl)].
This study of the three main vitamin D metabolites namely 25-(OH) D, 24, 25-(OH) 2D and 1, 25-(OH) 2D includes (1) a summary of the usual assay techniques, (2) a discussion about the concentrations and the role of these metabolites during the neonatal and childhood periods, (3) a report of the results obtained during the past seven years in our laboratory with comments on the interest and limits of these assays for the diagnosis of different types of rickets.
24,25-Dihydroxyvitamin D 3↗
[Serum concentrations of vitamin D metabolites in idiopathic juvenile osteoporosis (author's transl)].
This report concerns a 13 year old girl with the clinical and radiological features of mild idiopathic juvenile osteoporosis. In this patient, no alteration was detected in serum calcium (total + ionized) and phosphorus concentration, serum alkaline phosphatase activity, nor in urinary calcium and phosphorus excretions. Plasma concentrations of cortisol were normal during daytime and sleep. Circulating immunoreactive parathyroid hormone was normal or low. The serum 25-(OH)D and 24,25-(OH)2D concentrations were below the normal range, and the 1,25-(OH)2D concentrations were above the normal range (720 pmol/l) at the beginning of the investigation. All vitamin D metabolites concentrations returned to normal values at the time of radiological recovery and after calcium and 25-(OH)D3 supplementation. A possible relationship between alterations of bone and of circulating vitamin D metabolites is discussed.
Adolescent↗
A vitamin D-dependent calcium-binding protein in rat skin.
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Animals↗
Chronic hypophosphatemia in kidney transplanted children and young adults.
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Adult↗
In vitro effects of vitamin D3 metabolites on rat calvaria cAMP content.
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Animals↗
Plasma vitamin D metabolites in a patient with sporadic hypophosphataemic osteomalacia (adult-onset type).
Sporadic hypophosphataemic osteomalacia (adult-onset type) was demonstrated in a 40-year-old man on the basis of severe osteomalacia, hypophosphataemia, hyperphosphaturia and glycinuria. Plasma immunoreactive parathyroid hormone (iPTH) concentration was 9.3 ng prot./ml (normal range: 4-8 ng prot./ml). Plasma 25-hydroxy-vitamin D and 24,25-dihydroxy-vitamin D concentrations were 11 and 2.4 ng/ml respectively. Basal 1 alpha,25-dihydroxy-vitamin D concentrations were slightly elevated (116 and 96 pg/ml) and increased to 240 pg/ml after 3 days on a low-phosphorus diet. The patient was put on oral treatment with 25-hydroxycholecalciferol (100 microgram per day) and phosphorus (1500 mg per day). On the 4th month on treatment, a clinical improvement was apparent. Plasma 25(OH)D was 44 ng/ml, plasma 1,25(OH)2D was 256 pg/ml. However, plasma phosphorus remained low (0.77 mmol/l). On the 9th month of treatment a radiological improvement was evident despite a persistent hypophosphataemia (0.68 mmol/l). These facts suggest in our patient the existence of a vitamin D-independent renal phosphorus leak.
Adult↗