Disease relevance of D01518

• Treatment of advanced myelodysplastic syndrome with alfacalcidol [1].
• Identification and treatment of osteomalacia are inseparably bound; the response of varying degrees of subclinical disease to treatment with vitamin D or alfacalcidol is described here [2].
• Here we provide histomorphometric as well as biochemical evidence that alfacalcidol suppresses osteoclastic bone resorption in an ovariectomized rat model of osteoporosis [3].
• Skeletal biopsies were improved and sometimes normalized by using calcitriol or alfacalcidol in daily doses of 0.25 to 0.5 microgram/d, and the incidence of hypercalcemia was quite low with these doses [4].
• Patients treated with i.v. ibandronate injections also experienced less back pain (p<0.001) and less height loss (p=0.001) than those receiving oral alfacalcidol [5].

Psychiatry related information on D01518

• Dementia in Idiopathic hypoparathyroidism. Rapid efficacy of alfacalcidol [6].
• The 3-year rates of patients with at least one new fracture of any kind were 19.4% among those treated with alfacalcidol and 40.65% with vitamin D (risk reduction 0.52, 95% CI 0.25-0.71, P=0.001) [7].

High impact information on D01518

• Sustained haematological response to high-dose oral alfacalcidol in patients with myelodysplastic syndromes [8].
• RESULTS: Compared with baseline, the 2-year mean changes in bone mineral density were 2.0% for hormone replacement therapy, -0.5% for etidronate, 1.6% for calcitonin, -3.6% for alfacalcidol, -1.9% for vitamin K, and -3.3% for control [9].
• Treatment of OVX mice with pharmacologic doses of alfacalcidol does not increase RANKL expression, whereas toxic doses that cause hypercalcemia markedly reduce the expression of RANKL [10].
• Here, we show that alfacalcidol, a prodrug metabolized to 1alpha,25(OH)2D3, suppresses bone resorption at pharmacologic doses that maintain normocalcemia in an ovariectomized (OVX) mouse model of osteoporosis [10].
• Marrow cultures from alfacalcidol- or estrogen-treated OVX mice showed significantly less osteoclastogenic potential compared with those from vehicle-treated OVX mice, suggesting that the pool of osteoclast progenitors in the marrow of vitamin D-treated mice as well as estrogen-treated mice was decreased [10].

Chemical compound and disease context of D01518

• 17beta-Estradiol, which suppresses bone resorption to the same extent as alfacalcidol, causes a parallel reduction in the biochemical and histomorphometric markers of bone formation [3].
• METHODS: We compared the risk of death between regular users (n = 162) and non-users (n = 80) of oral 1alpha-hydroxyvitamin D3 (alfacalcidol) in a cohort of ESRD patients undergoing haemodialysis for a follow-up of 61 +/- 23 months [11].
• Multiple linear regression analysis with plasma oxalate as the dependent variable showed highly significant associations with the dose of ascorbic acid, dose of alfacalcidol, and plasma creatinine, and weaker associations with serum phosphate, serum calcium, and body weight [12].
• PATIENTS AND METHODS: Patients with glioblastomas and anaplastic astrocytomas were enrolled in a phase II trial involving surgery or biopsy, radiotherapy (64 Gy), chemotherapy with VM26-CCNU or fotemustine, and alfacalcidol at the daily dose of 0.04 microg/kg [13].
• CONCLUSIONS: During this 18-month trial in patients with rheumatic diseases, alendronate was more effective in the prevention of glucocorticoid-induced bone loss than was alfacalcidol [14].

Biological context of D01518

• Although she had been effectively treated since one month postpartum with 1 alpha-hydroxycholecalciferol [1 alpha(OH)D3, alfacalcidol], her mean alkaline phosphatase (EC 3.1.3.1) activity in serum increased to 3680 U/L from a stable value [335 (SD 50) U/L; n = 12] within three weeks, then returned to baseline over the ensuing four months [15].
• We therefore carried out a prospective study over 18 months to examine the direct effect of high-dose alfacalcidol on erythropoiesis in erythropoietin (rHuEpo)-dependent anaemic patients on HD for more than 6 months with moderate hyperparathyroidism [16].
• Intravenous alfacalcidol improves insulin resistance in hemodialysis patients [17].
• Alfacalcidol 1 microg/day fully prevented vertebral bone loss over 3 years in women after the first year of menopause [18].
• The expanded understanding of the pathogenesis of glucocorticoid- induced osteoporosis with its disturbed calcium homeostasis and the pharmacological effects of alfacalcidol, which counteract such iatrogenic bone loss, contribute to the understanding of its clinical efficacy in this most frequent form of secondary osteoporosis [19].

Anatomical context of D01518

• ED-71 increased bone mass at the lumbar vertebra to a greater extent than alfacalcidol, while enhancing calcium absorption (indicated by urinary calcium excretion) and decreasing serum PTH levels to the same degree as alfacalcidol [20].
• Twenty-eight fifth lumbar vertebrae (L-5) were obtained from 10-month-old female rats, comprised of ovariectomized (ovx, n = 6), sham operated (n = 7), and alfacalcidol-treated after ovx (0.1 microg/kg [n = 8] and 0.2 microg/kg [n = 7]) groups [21].
• 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 [22].
• The study was performed to clarify the effects of active vitamin D (alfacalcidol) and/or alendronate (ALN) on bone tissue turnover in glucocorticoid (GC)-treated growing minipigs [23].
• We studied the effect of alfacalcidol on lymphocyte phenotype [24].

Associations of D01518 with other chemical compounds

• This prospective, open label, active controlled, randomized clinical study compared the effects of oral alendronate (10 mg daily) and alfacalcidol (1 microg daily) on bone mineral density (BMD), safety, and tolerability in 134 males with primary established osteoporosis [25].
• We have therefore performed a randomized, single masked study comparing the effects of alfacalcidol treatment (0.25 micrograms twice daily) and vitamin D2 supplementation (500-1000 units daily) on calcium absorption and bone turnover in 46 elderly women (median age 69 years, range 64-79 years) with radiological evidence of vertebral fractures [26].
• Falecalcitriol was found to be superior to alfacalcidol in suppression of PTH levels in patients with moderate to severe secondary hyperparathyroidism when it is administered in equivalent doses that might maintain similar serum calcium levels [27].
• All randomized, controlled, double-blinded trials comparing oral native vitamin D and its analogs, alfacalcidol or calcitriol, to placebo or head-to-head trials in primary or corticosteroids-induced osteoporosis were included in the meta-analysis [28].
• We investigated the effects of conjugated estrogens as an add-back replacement drug, incadronate sodium as a bisphosphonate, and alfacalcidol as a vitamin D(3) analog on femoral bone mineral density (BMD) and bone mineral content (BMC) in female rats chronically treated with the gonadotropin-releasing hormone (GnRH) agonist leuprorelin acetate [29].

Gene context of D01518

• Two patients with Kearns-Sayre Syndrome and hypoparathyroidism were treated with alfacalcidol (1a-OH D3) and total serum calcium concentration remained within normal range for a long period [30].
• The main results of this review show that alfacalcidol may have a wider range of therapeutic applicability, beyond simply restricting it to patients in hemodialysis or peritoneal dialysis with high serum levels of intact PTH [31].
• D-hormone analog alfacalcidol: an update on its role in post-menopausal osteoporosis and rheumatoid arthritis management [31].
• A comparison of oral and intravenous alfacalcidol in the treatment of uremic hyperparathyroidism [32].
• Supplementation with alfacalcidol significantly decreased serum concentration of sTNFR-II from 23.8 +/- 4.38 to 19.7 +/- 3.93 ng/ml (p < 0.001) but did not alter serum IL-6 concentration [33].

Analytical, diagnostic and therapeutic context of D01518

• In this study, 16 hemodialysis patients with mild to moderate hyperparathyroidism were assigned, after a 4-wk run-in period, to receive a 6-wk course of either thrice-weekly i.v. or p.o. alfacalcidol (initial dose, 4 micrograms) [32].
• Fourteen continuous ambulatory peritoneal dialysis patients with 2'hpt were treated with pulse oral alfacalcidol and calcium carbonate and dialyzed with a 1.0-mmol (n = 7) or a 1.25-mmol (n = 7) dialysate calcium [34].
• Comparative efficacy of hormone replacement therapy, etidronate, calcitonin, alfacalcidol, and vitamin K in postmenopausal women with osteoporosis: The Yamaguchi Osteoporosis Prevention Study [9].
• Use of alfacalcidol early after transplantation is safe and well tolerated [35].
• Early bone loss that occurs during the first 1 yr after renal transplantation could be prevented by alfacalcidol [35].

References