A comparison of the toxicity of ergocalciferol and cholecalciferol in rhesus monkeys (Macaca mulatta).
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Rats maintained on low-protein rachitogenic diets show increased intestinal calcium transport, serum inorganic phosphate and increased endochondral calcification responses to calciferol, 25-hydroxycholecalciferol (25-OH-CC) and 1,25-dihydroxycholecalciferol (1,25-(OH)2CC). Because enhanced responses are observed with 1,25-dihydroxycholecalciferol as well as its precursors, it is unlikely that the effect of dietary protein is mediated by a change in the calciferol-25-hydroxylase and the 25-hydroxycholecalciferol-1 alpha-hydroxylase. Instead, it appears that either metabolism of 1,25-dihydroxycholecalciferol or its activity in the target organs is affected.
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Fast-growing heavy (White Rock) chicks, fed a vitamin D-deficient diet, exhibited a higher activity of kidney 25-hydroxycholecalciferol-1-hydroxylase (1-hydroxylase) than slow-growing light (White Leghorn x Rhode Island Red) chicks fed the same diet. 1-Hydroxylase and duodenal calcium-binding protein (CaBP) declined with age. Feeding of low energy diets with or without vitamin D resulted in a slower rate of growth and reduced 1-hydroxylase activity and CaBP concentration. Severe dietary restriction of either calcium or phosphorus resulted in a lower growth rate as well as a duodenal CaBP as compared to a moderate mineral restriction. The severe dietary calcium restriction also resulted in a lower 1-hydroxylase activity than that resulting from a moderate restriction. The results clearly indicate that high 1-hydroxylase activity and a high intestinal CaBP are associated with a high growth rate.
Seventeen undialysed adult patients with chronic renal failure took part in a controlled study of the effects of 1,25(OH)2D3 and D3. After a 6-month observation period the patients were allocated at random to two groups for 6 months of treatment with either 1,25(OH)2D3 (mean dose 0.5 microgram daily) or D3 (dose 100 microgram daily). Treatment was then discontinued and the patients were studied for a further 6 months. Serum iPTH was decreased in both groups but most markedly in the 1,25(OH)2D3 group in which the iPTH values became normal. Serum creatinine increased during treatment in both groups. In the group receiving 1,25(OH)2D3 this was coupled to an increase in serum calcium within the normal range. Our data demonstrate that 1,25(OH)2D3 treatment in patients with chronic renal failure leads to a further reduction in renal function, which may be partially reversible. Physicians should therefore be reluctant to give vitamin D analogues to patients with chronic renal failure unless they have severe symptomatic renal osteodystrophy.
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OBJECTIVE: To assess whether supplementation with calcium and cholecaliferol (vitamin D3) reduces the risk of fracture in women with one or more risk factors for fracture of the hip. DESIGN: Pragmatic open randomised controlled trial. SETTING: Practice nurse led clinics in primary care. PARTICIPANTS: 3314 women aged 70 and over with one or more risk factors for hip fracture: any previous fracture, low body weight (< 58 kg), smoker, family history of hip fracture, or fair or poor self reported health. INTERVENTION: Daily oral supplementation using 1000 mg calcium with 800 IU cholecaliferol and information leaflet on dietary calcium intake and prevention of falls, or leaflet only (control group). MAIN OUTCOME MEASURES: Primary outcome measure was all clinical fractures and secondary outcome measures were adherence to treatment, falls, and quality of life (measured with the SF-12). RESULTS: 69% of the women who completed the follow-up questionnaire at 24 months were still taking supplements (55% with inclusion of randomised participants known to be alive). After a median follow-up of 25 months (range 18 to 42 months), clinical fracture rates were lower than expected in both groups but did not significantly differ for all clinical fractures (odds ratio for fracture in supplemented group 1.01, 95% confidence interval 0.71 to 1.43). The odds ratio for hip fracture was 0.75 (0.31 to 1.78). The odds of a woman having a fall at six and 12 months was 0.99 and 0.98, respectively. Quality of life did not significantly differ between the groups. CONCLUSION: We found no evidence that calcium and vitamin D supplementation reduces the risk of clinical fractures in women with one or more risk factors for hip fracture. Registration ISRCTN26118436, controlled trials registry.
25-Hydroxyvitamin D (25-OHD) levels were measured in 39 patients with metabolic bone disease or hypoparathyroidism who had been treated with a constant high dose of vitamin D2 or D3 for at least 12 weeks. Plasma 25-OHD levels rose with increasing dosage, the relationship between dose and plasma level being approximately linear whether or not the dose was expressed on a weight-corrected basis. A therapeutic range of 25-OHD to be expected when patients with these conditions are treated with vitamin D has been established. There may be certain exceptions in which plasma 25-OHD levels within the range are associated with either an inadequate response to treatment or, conversely, the hypercalcaemia of vitamin D toxicity. There was no correlation between plasma calcium level and 25-OHD concentration in the group of patients studied. There was also no difference between the dose/25-OHD relationship of patients treated with vitamin D2 and that of patients receiving vitamin D3. Ten patients were started on treatment with large doses of vitamin D during the period of the study. The rate of rise of plasma 25-OHD was followed during treatment. The incremental rise in 25-OHD was calculated at the end of the first week of treatment in terms of dose per unit body weight. The rate of rise of plasma 25-OHD level was highly correlated with the dose used. Plasma 25-OHD levels after one weeks' treatment were only 15-20% of the expected steady-state level on the same dosage. The importance of a high priming dose when a rapid response is needed is thus emphasised.
In vitro binding of 25-hydroxycholecalciferol (25-(OH)D3) and 1alpha,25-dihydroxycholecalciferol (1,25-(OH)2D3) was studied in the duodenal mucosa cytosol of rachitic rats: both 25-(OH)D3 and 1,25-(OH)2D3 bind to a macromolecule (sedimentation coefficient 5.5 to 6 S in low or high ionic strength) with a high affinity (KD at 4 degrees C = 1.2 X 10-9M and 2 x 10-9M, respectively). In addition, it is concluded from competition and chase experiments that 25-(OH)D3 binding sites differ from that for 1,25-(OH)2D3.
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Tibiae were removed from 300 75-wk-old laying hens for tibia strength analysis using two methods, direct photon absorptiometry and tibia breaking strength. Left tibiae with flesh intact were used for bone density determination with direct photon absorptiometry. Right tibiae were cleaned and dried for determination of tibia weight and tibia breaking strength. Partial correlation coefficients were estimated among bone density, tibia breaking strength, tibia weight, and body weight. A significant correlation was observed between tibia breaking strength and bone density measurements (r = .66, P less than or equal to .0001). Tibia weight and tibia breaking strength were also significantly correlated (r = .62, P less than or equal to .0001), as well as bone weight and bone density (r = .71, P less than or equal to .0001). Tibia weight and BW were also significantly correlated (r = .66, P less than or equal to .0001), necessitating covariance adjustment for BW. Bone densitometry measurements are less variable than tibia breaking strength measurements, and bone densitometry does not require cleaning bones of flesh before measurement.