Alfacalcidol

Alfacalcidol is an analogue of Vitamin D and a potent inhibitor of bone resorption [1].

Alfacalcidol has been revealed to play a part in bone and mineral homeostasis via binding to the VDR (vitamin D receptor) in calcium-related target organs, such as intestine, bone, kidney and parathyroid gland. In addition, in a high bone-turnover state after OVX, Alfacalcidol has been reported to inhibit osteoclastic bone resorption at pharmacological doses that do not cause hypercalcemia. Apart from these, Alfacalcidol has shown the stimulative effect to the bone formation. Furthermore, Alfacalcidol has been found to enhance bone mass and bone strength at given serum and urinary calcium levels in the OVX model.

References:
[1] Shiraishi A1, Takeda S, Masaki T, Higuchi Y, Uchiyama Y, Kubodera N, Sato K, Ikeda K, Nakamura T, Matsumoto T, Ogata E. Alfacalcidol inhibits bone resorption and stimulates formation in an ovariectomized rat model of osteoporosis: distinct actions from estrogen. J Bone Miner Res. 2000 Apr;15(4):770-9.

Efficacy of alfacalcidol and alendronate on lumbar bone mineral density in osteoporotic patients using proton pump inhibitors.[Pubmed:27446535]

Biomed Rep. 2016 Aug;5(2):165-170.

It has been indicated that proton pump inhibitor (PPI) use is associated with a loss of the anti-fracture efficacy of alendronate (AD). However, there are few prospective studies that have investigated the efficacy of AD on lumbar bone mineral density (BMD) in osteoporotic patients who are using PPIs. Thus, the aim of the present study was to investigate the efficacy of Alfacalcidol (AC) and AD on lumbar BMD in osteoporotic patients using PPIs. A prospective, randomized, active control study enrolled such osteoporotic patients (age, >/=50 years). The patients were randomly assigned to receive AC (1 microg/day) or AD (35 mg/week) and were followed up for one year. Patient profiles were maintained, and lumbar BMD, bone-specific alkaline-phosphatase (BAP) and collagen type-I cross-linked N-telopeptide (NTX), upper gastrointestinal endoscopy results, and the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) were evaluated. Percentage changes in lumbar BMD, NTX, BAP, and change in FSSG score from baseline to the end of one year of treatment were investigated. Sixteen patients were eligible for analysis (eight assigned to receive AC, eight assigned to receive AD). The percentage change in lumbar BMD from baseline to the end of treatment was -0.4+/-4.0% for the AC group vs. 6.8+/-6.3% for the AD group (P=0.015). No significant percentage change of BAP and NTX between the two groups was observed. Subsequent to one year of treatment, the FSSG score did not change from the baseline values for either study group, and no new bone fractures or esophagitis were observed in either group of patients. The findings demonstrated that in osteoporotic patients using concomitant PPIs, there was a greater increase in lumbar BMD after one year of treatment with AD compared with AC. However, the number of study subjects was small; thus, further, large prospective studies are required to determine the effect of AD in osteoporotic patients using concomitant PPIs.

Effects of 1alpha-Calcidol (Alfacalcidol) on Microvascular Endothelial Function, Arterial Stiffness, and Blood Pressure in Type II Diabetic Nephropathy Patients.[Pubmed:26749451]

Microcirculation. 2016 Jan;23(1):53-61.

OBJECTIVES: To determine the effects of six months Alfacalcidol on microvascular endothelial function, arterial stiffness, and BP in DN patients. METHODS: Twenty-eight DN patients on Alfacalcidol, 0.25 mug daily for six months were compared to 32 controls on conventional treatment. Measurements of microvascular endothelial function, arterial stiffness [AIx and PWV], hsCRP, and BP were performed; differences between baseline and six months treatment were evaluated. RESULTS: No difference was seen in microvascular endothelial function for both groups after six months. Improvement in CSBP (p = 0.027) with trends of improvement in AIx (p = 0.063), PWV (p = 0.075), and systolic BP (p = 0.088) were seen in the Alfacalcidol group with no changes observed in controls. Subgroup analysis of Alfacalcidol group showed that vitamin D-deficient patients had better response to treatment. hsCRP level remained unchanged in Alfacalcidol group; significant increase was however seen in controls. CONCLUSION: Alfacalcidol did not have an effect on microvascular endothelial function in DN patients. Alfacalcidol significantly improved CSBP with trends of improvement in arterial stiffness and peripheral BP. Alfacalcidol appears to be more beneficial in vitamin D-deficient patients.

Effects of combined alendronate and alfacalcidol on prevention of fractures in osteoporosis patients: a network meta-analysis.[Pubmed:26550211]

Int J Clin Exp Med. 2015 Aug 15;8(8):12935-41. eCollection 2015.

BACKGROUND: Published literatures report controversial results about the effect of combined treatment with alendronate and Alfacalcidol for the prevention of fractures in osteoporosis patients. METHODS: Seven common databases were searched for related randomized controlled trials published up to April, 2015. Bayesian random effects network meta-analysis was used to assess the pairwise odds ratios (OR), 95% credible intervals (CI). RESULTS: Thirteen randomized controlled trials were identified (3710 patients). The network meta-analysis results indicated that combining treatment with alendronate and Alfacalcidol was significantly better to prevent bone fractures in osteoporosis patients than alendronate (OR=0.53, 95% CI: 0.19-0.95) and Alfacalcidol (OR=0.25, 95% CI: 0.08-0.49). In addition, there was no significant difference for adverse events among the three therapeutic regimen. CONCLUSIONS: Combined treatment with alendronate and Alfacalcidol was more active than the monotherapies in preventing bone fractures in osteoporosis patients. Large-scale randomized, controlled trials are recommended to confirm the result.

Conversion of oral alfacalcidol to oral calcitriol in the treatment of secondary hyperparathyroidism in chronic hemodialysis patients.[Pubmed:27822674]

Int Urol Nephrol. 2017 Feb;49(2):325-328.

PURPOSE: The optimal vitamin D3 therapy for the treatment of secondary hyperparathyroidism (SHPT) in chronic hemodialysis patients is still controversial. Recent studies suggest that uremia in end-stage renal disease is associated with enzymatic hepatic dysfunction altering 25-hydroxylation of vitamin D3. The goal of our study was to compare the efficacy of calcitriol, the fully hydroxylated active form of vitamin D3, to Alfacalcidol which needs 25-hydroxylation to be effective, for the treatment of SHPT in chronic hemodialysis patients. METHODS: We retrospectively reviewed 45 chronic hemodialysis patients who were switched from oral Alfacalcidol to oral calcitriol for the treatment of SHPT. Parathyroid hormone (PTH), serum calcium and serum phosphorus levels were compared pre- and post-conversion using paired Student's t tests. RESULTS: The mean dose of active vitamin D3 decreased from 3.50 mcg/week at baseline to 2.86 mcg (P < 0001) after the switch from Alfacalcidol to calcitriol. PTH significantly decreased from 94.4 to 82.6 pmol/L (-11.8 pmol/L, P = 0.02). The mean corrected calcium increased from 2.17 to 2.25 mmol/L (+0.08 mmol/L, P < 0.001) without any clinically significant hypercalcemia, and phosphorus levels were stable. Results were similar in a subgroup of patients (n = 17) for whom the medication was administrated during the hemodialysis session, ensuring a complete compliance. CONCLUSIONS: According to our study, calcitriol in equal dosage is more effective than Alfacalcidol in lowering serum PTH level in chronic hemodialysis patients. This suggests that calcitriol may be the optimal active vitamin D3 for the treatment of SHPT in chronic hemodialysis patients.

Alfacalcidol (1-hydroxycholecalciferol) is a vitamin D active metabolites, acts as a non-selective VDR activator medication, and widely be used in the management of osteoporosis.

Alfacalcidol,41294-56-8,1-Hydroxycholecalciferol,Natural Products,VD/VDR, buy Alfacalcidol , Alfacalcidol supplier , purchase Alfacalcidol , Alfacalcidol cost , Alfacalcidol manufacturer , order Alfacalcidol , high purity Alfacalcidol