Sevelamer hydrochloride with or without alphacalcidol or higher dialysate calcium vs calcium carbonate in dialysis patients: an open-label, randomized study.
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BACKGROUND: Sevelamer hydrochloride was recently proposed as a phosphate binder to prevent hypercalcaemia in place of calcium alkaline salts in dialysis patients. So far, it has been evaluated only in patients receiving calcitriol, without comparison with CaCO(3) alone, although the latter was found to be as effective as the combination of calcitriol and Al(OH)(3) in suppressing parathyroid hormone (PTH) without inducing hypercalcaemia and to have a better lowering effect on serum phosphate. Moreover, this bile salt binder may decrease serum 25-OH vitamin D. Therefore, we compared for 5 months two strategies for controlling moderate hyperparathyroidism: CaCO(3) alone vs sevelamer in conjunction with measures to increase calcium balance. METHODS: Forty-two patients were randomized: 21 continued their treatment with 4.8 g/day CaCO(3) and 21 were switched to sevelamer (initial dose: 2.4 g/day, increased to 4.4 g/day). Each month, when serum-corrected calcium decreased below 2.30 mmol/l, dialysate calcium was increased or alphacalcidol was given at each dialysis session, according to serum PO(4) levels. The following parameters were monitored: serum Ca, PO(4), bicarbonate and protein, weekly; and serum PTH, 25-OH vitamin D and total, LDL and HDL cholesterol monthly. RESULTS: Except for higher serum phosphate at month 1, lower serum bicarbonate at month 2 and lower LDL cholesterol at month 5 in the sevelamer group, no difference was found between the two groups. Compared with baseline levels, PTH increased and 25-OH vitamin D decreased significantly in both groups, these two parameters being inversely correlated. CONCLUSIONS: Given comparable control of plasma calcium, phosphate and 25-OH vitamin D, PTH control is comparable in both strategies. Sevelamer does not induce greater vitamin D depletion than CaCO(3). The transient decrease of serum bicarbonate after discontinuation of CaCO(3) in the sevelamer group suggests a less optimal prevention of acidosis. The sevelamer-induced decrease in LDL cholesterol gives this drug a potential advantage in cardiovascular prevention. (+info)
The effect of hepatectomy on the synthesis of 25-hydroxyvitamin D3.
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The metabolism of [3H]vitamin D3 in hepatectomized vitamin D-deficient rats has been studied. Hepatectomy drastically disrupts vitamin D3 metabolism as revealed by prolonged high levels of [3H] vitamin D3 in the plasma compartment even 12 h after dose in contrast to sham-operated controls. Some conversion of [3H] vitamin D3 to [3H]25-hydroxyvitamin D3 was detected in hepatectomized rats, but the amount was small in spite of the high circulating levels of [3H]vitamin D3. Since the liver initially takes up much of an administered dose in normal animals and the conversion of [3H]vitamin D3 to [3H]25-hydroxyvitamin D3 is small in hepatectomized rats in spite of high circulating [3H]-vitamin D3, it is concluded that the liver plays a major role in the metabolism of vitamin D3 to 25-hydroxy-vitamin D3. (+info)
A competitive protein binding assay for plasma 25-hydroxyvitamin D3 in normal children.
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In order to determine the plasma level of 25-hydroxyvitamin D3 (25-OH-D3) in Japanese children by the competitive protein binding assay, we studied binding proteins in D-deficient rats, and obtained the following results. 1) By using serum and kidney cytosol of D-deficient rats, we could obtain a standard curve with high sensitivity and accuracy which enabled us to determine the 25-OH-D3 level ranging from 0.5 to 5.0 ng. 2) The plasma 25-OH-D3 level was found to be 21.6+/-10.1 ng/ml (n=17) in healthy infants and children from 1 to 15 year-old, and 11.4+/-8.6 ng/ml (n=27) in mature neonates up to 2 days after delivery. (+info)
Effects of chronic administration of zonisamide, an antiepileptic drug, on bone mineral density and their prevention with alfacalcidol in growing rats.
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We investigated the effects of chronic administration of zonisamide, an antiepileptic agent, on bone metabolism in growing rats. Administration of zonisamide at a dose of 80 mg/kg per day, s.c. for 5 weeks significantly decreased bone mineral density (BMD) at the tibial metaphysis and the diaphysis. The percent rate of decrease in BMD at the tibial metaphysis and the tibial diaphysis was 9.2% and 5.0%, respectively. There was no significant difference between these groups in the growth of the rats. Treatment with zonisamide at a dose of 80 mg/kg increased serum pyridinoline level, a marker of bone resorption, while it does not affect the serum intact osteocalcin level, a marker of bone formation. Combined administration of alfacalcidol, an active vitamin D(3) metabolite, at a dose of 0.1 microg/kg per day with zonisamide prevented a decrease in BMD and showed an increase of serum pyridinoline levels. These results suggest that zonisamide may cause bone loss by accelerating bone resorption rather than inhibiting bone formation. Moreover, the bone loss induced by zonisamide could be prevented by combining zonisamide with alfacalcidol. (+info)
Three-monthly ibandronate bolus injection offers favourable tolerability and sustained efficacy advantage over two years in established corticosteroid-induced osteoporosis.
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OBJECTIVE: Corticosteroids are widely prescribed, although treatment-related side-effects are common. Of these adverse events (AEs), osteoporosis is considered the most serious. Currently, oral bisphosphonates are the standard treatment for corticosteroid-induced osteoporosis (CIO). However, intermittent intravenous (i.v.) therapy may have advantages, including lack of gastrointestinal AEs, improved bioavailability and increased compliance. This study investigated the efficacy and safety of 3-monthly i.v. ibandronate bolus injections in patients with established CIO. The results from a planned 2-yr interim analysis are reported. METHOD: In this controlled, prospective, open-label, parallel-group study, 104 patients (49 men and 55 women) with established CIO (mean T-score <-2.5 s.d. at the lumbar spine (L2-L4) received daily calcium (500 mg) plus either 3-monthly i.v. ibandronate (2 mg) bolus injections or oral daily alfacalcidol (1 micro g). The primary end-point was bone mineral density (BMD) change at the lumbar spine, femoral neck and calcaneus after 24 months. RESULTS: Compared with oral daily alfacalcidol, i.v. ibandronate produced significantly superior gains in mean (+/-s.d.) BMD at the lumbar spine (2.2+/-3.1 vs 11.9+/-7.4%; P<0.001), femoral neck (1.3+/-1.8 vs 4.7+/-4.0%; P<0.001) and calcaneus (7.6+/-3.8 vs 15.5+/-10.7%; P<0.0001) after 2 yr. Consistent with these BMD gains and, although the study was not powered for fractures, a trend towards a reduction in vertebral fractures and greater back pain relief was seen in the ibandronate group. The overall incidence of AEs was similar in the two treatment arms. CONCLUSIONS: Three-monthly i.v. ibandronate bolus injections are significantly superior to alfacalcidol in the treatment of CIO. These data confirm the potential of ibandronate for the treatment of osteoporosis associated with corticosteroid use. The ease of administration, lack of AEs and good compliance associated with intermittent i.v. ibandronate make it a potentially valuable alternative to oral bisphosphonate therapy for the treatment of CIO. (+info)
Whole-body in-vivo neutron activation analysis in assessing treatment of renal osteodystrophy with 1-alpha-hydroxycholecalciferol.
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Four selected adults with different patterns of osteodystrophy receiving regular dialysis were treated with 1-alpha-hydroxycholecalciferol (1-alpha-OHD3) 0-5-2 mug/day for 10 to 12 months. In two patients, one with osteitis fibrosa and the other with osteomalacia, significant biochemical, radiological, and histological improvements occurred, and total body calcium measured by in-vivo neutron activation analysis increased. In two patients, in whom there were no increases of whole-body calcium, neither biochemical improvement nor healing of bone lesions occurred during the study; in one of these patients the effect of 1-alpha-OHD3 on bone resorption may have contributed to loss of body calcium and deterioration of bone disease. 1-alpha-OHD3 may therefore be a valuable adjunct in the treatment of only some patients with renal osteodystrophy. Whole-body in-vivo neutron activation seems to provide a sensitive and non-invasive index of early response to treatment. (+info)
Vitamin D3 and calcium to prevent hip fractures in the elderly women.
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BACKGROUND: Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known. METHODS: We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/- SD] age, 84 +/- 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women. RESULTS: Among the women who completed the 18-month study, the number of hip fractures was 43 percent lower (P = 0.043) and the total number of nonvertebral fractures was 32 percent lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3-calcium group, the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months (P < 0.001) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value (P < 0.001). The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group (P < 0.001). CONCLUSIONS: Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women. (+info)
Parathyroid hormone-related protein as a cause of hypercalcemia in a B-cell type malignant lymphoma.
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Hypercalcemia occurred in a patient with non-Hodgkin's (B-cell type) lymphoma when generalized lymphadenopathy developed. Despite low normal plasma parathyroid hormone (PTH), nephrogenous cAMP (NcAMP) was not suppressed, and serum and urine PTH-related protein (PTH-rP) levels were elevated. The plasma level of 1,25(OH)2D was within normal range. The combined chemotherapies successfully reduced the tumor size, serum Ca, PTH-rP, and lactic dehydrogenase. Serum osteocalcin was suppressed while the patient was hypercalcemic, and increased after chemotherapy. In the extract of the tumor tissue obtained post mortem, bioactivity stimulating the production of cAMP in osteoblasts was demonstrated along with the immunoreactive PTH-rP. This is the first report of a B-cell lymphoma producing PTH-rP and its association with humoral hypercalcemia of malignancy. (+info)