Clinical efficacy and safety of use of alfacalcidol and calcitriol in daily endocrinological practice.

This paper aims to discuss and compare 2 vitamin D derivatives available on the Polish market, alfacalcidol and calcitriol, in the context of their effectiveness and safety in endocrine patients. Both above-mentioned substances find a number of applications, including in hypoparathyroidism, which is one of the most common indications for their use. We would also like to draw the reader's attention to the fact that there are quite a lot of reports in the literature on the positive effect of alfacalcidol and calcitriol on maintaining bone mass and the risk of fractures, which may bring additional potential benefits to our patients.

Randomized Trial of Etelcalcetide for Cardiac Hypertrophy in Hemodialysis.

[Figure: see text].

Eldecalcitol is superior to alfacalcidol in maintaining bone mineral density in glucocorticoid-induced osteoporosis patients (e-GLORIA).

INTRODUCTION: Eldecalcitol increases bone mineral density (BMD) and reduces vertebral fracture in patients with primary osteoporosis. However, the effect of eldecalcitol on BMD and fracture in glucocorticoid-induced osteoporosis (GIO) patients is unknown. This study was undertaken to compare the effect of eldecalcitol on BMD and fracture with that of alfacalcidol in GIO patients. MATERIALS AND METHODS: A randomized, open-label, parallel group study was conducted to identify the effectiveness and safety of monotherapy with 0.75 µg eldecalcitol compared with 1.0 µg alfacalcidol in GIO patients. RESULTS: Lumbar spine BMD increased with eldecalcitol, but decreased with alfacalcidol at 12 and 24 months (between group difference 1.29%, p < 0.01, and 1.10%, p < 0.05, respectively). Total hip and femoral neck BMD were maintained until 24 months by eldecalcitol, but decreased by alfacalcidol (between group difference 0.97%, p < 0.05 and 1.22%, p < 0.05, respectively). Both bone formation and resorption markers were more strongly suppressed by eldecalcitol than by alfacalcidol. Eldecalcitol showed better effect on BMD than alfacalcidol in patients with no prevalent fracture and BMD > 70% of the young adult mean, and with ≤ 3 months of previous glucocorticoid treatment. No significant difference in the incidence of vertebral fracture was found, and the incidence of adverse events was similar between the two groups. CONCLUSIONS: Eldecalcitol was more effective than alfacalcidol in maintaining BMD in GIO patients. Because eldecalcitol was effective in patients with no or short-term previous glucocorticoid treatment, as well as those without prevalent fracture or low BMD, eldecalcitol can be a good candidate for primary prevention of GIO. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000011700.

Minodronate combined with alfacalcidol versus alfacalcidol alone for glucocorticoid-induced osteoporosis: a multicenter, randomized, comparative study.

INTRODUCTION: This study compared the clinical usefulness of minodronate (50 mg/4 weeks) plus alfacalcidol (1 µg/day) (Group M) with that of alfacalcidol alone (1 µg/day) (Group A) for treating glucocorticoid-induced osteoporosis. MATERIALS AND METHODS: The primary endpoints were the changes from baseline in lumbar spine (LS) bone mineral density (BMD) and the cumulative incidence of vertebral fracture at 24 months; secondary endpoints included the changes from baseline in total hip (TH) BMD and bone turnover markers. RESULTS: Of 164 patients enrolled, 152 (Group M, n = 75; Group A, n = 77) were included in the analysis of efficacy. At each time point and at 24 months, LS BMD and TH BMD were significantly higher in Group M than in Group A. The 152 patients were divided into two subgroups that were previously treated with glucocorticoids for ≤ 3 months or > 3 months. In both subgroups, the changes from baseline in LS BMD and TH BMD from baseline at 24 months had increased more in Group M than in Group A. There were no differences found in the incidence of vertebral fracture between the groups, because the number of enrolled patients was lesser than that initially expected. In Group M, both bone formation and resorption markers significantly decreased from baseline at 3 months and maintained at 6, 12, and 24 months. CONCLUSIONS: Minodronate plus alfacalcidol was more effective than alfacalcidol alone in increasing BMD and was effective in increasing BMD for both prevention and treatment. Therefore, minodronate can be a good candidate drug for the treatment of glucocorticoid-induced osteoporosis.

Auditing the Efficacy and Safety of Alfacalcidol and Calcium Therapy in Idiopathic Hypoparathyroidism.

CONTEXT: Patients with hypoparathyroidism are treated with vitamin D and calcium. PTH is an emerging option because of its physiological action. It is important to assess the efficacy and shortcomings of conventional therapy. OBJECTIVE: We assessed the efficacy and safety of alfacalcidol in a large cohort of patients with idiopathic hypoparathyroidism (IH) and identified a subset who could be treated without oral calcium. DESIGN AND SETTING: Observational study at tertiary care center. SUBJECTS AND METHODS: We assessed 92 patients with IH who were receiving alfacalcidol and oral calcium to maintain an optimal serum total calcium level of 8.0 to 8.5 mg/dL during routine follow-up. Patients with suboptimal control were provided free medicines and followed up frequently. Oral calcium and alfacalcidol doses were titrated sequentially to determine the minimum doses for optimal calcium control. Serum phosphate level, 1,25-dihydroxyvitamin D, fractional excretion of phosphorus (FEPh), and hypercalciuria (urine calcium-to-creatinine ratio, >0.2) were assessed at each step of titration. RESULTS: Only 38% of patients had optimal calcium control during routine follow-up. With good compliance, all achieved optimal serum calcium and 1,25-dihydroxyvitamin D levels and 43% of patients could stop taking oral calcium. Hyperphosphatemia, hypercalciuria, and low FEPh persisted at all stages of therapy. Serum phosphorus levels normalized when the serum calcium level increased to 9.9 mg/dL, but this level of serum total calcium was associated with hypercalciuria in 90% of patients. CONCLUSION: Alfacalcidol is effective in achieving calcemic control in IH. Calcemic control without oral calcium was achieved in 43% of patients receiving alfacalcidol. However, optimal calcium control was associated with hyperphosphatemia and hypercalciuria in most patients.

Efficacy and safety of alfacalcidol in Chinese postmenopausal women aged over 65 with osteoporosis or osteopenia: An open label, non-comparative, post marketing observational study.

This study aimed to explore the therapeutic efficacy and safety of alfacalcidol among Chinese postmenopausal women (age >65 years) with osteoporosis or osteopenia.A total of 62 postmenopausal women with osteoporosis or osteopenia (>65 years) were recruited from urban residential community of Beijing. The patients daily took oral calcium and alfacalcidol (Alpha D3, 1 µg) for 9 months. Safety and efficacy assessments were performed at baseline and regular intervals. Alfacalcidol was adjusted to a daily dose of 0.5 µg in case of hypercalcemia or hypercalciuria.A significant improvement in "timed up and go test" and "chair rising test" was achieved 3 months after treatment. Significant decreases in bone turnover markers were observed 3 months after the treatment and lasted throughout the study. Nineteen patients discontinued due to adverse events (17 hypercalciuria, 1 hydronephrosis, and 1 stomach ache), while alfacalcidol was adjusted to a daily dose of 0.5 µg in 18 patients (29.0%). Increased serum creatinine was observed when compared to baseline (P <.001), but all the values were in normal range.The treatment with 1 µg alfacalcidol can significantly improve muscle function and bone metabolism. Regular monitoring of urine calcium and timely dosage-adjustments are very important to guarantee the safety of alfacalcidol treatment in Chinese menopausal women.

Caso clínico: hipofosfatasia de la niñez. Seguimiento clínico / Clinical case: childhood hypophosphatasia. Clinical follow-up

La hipofosfatasia (HP) es una enfermedad congénita, causada por mutaciones con pérdida de función en el gen ALPL que codifica la isoenzima no específica de tejido de la fosfatasa alcalina (TNSALP). Su expresión clínica es muy variable, desde casos de muerte intraútero por alteración grave de la mineralización ósea, hasta casos solo con caída prematura de la dentición. Se presenta el caso clínico de un varón al que se le diagnosticó odontohipofosfatasia a los 30 meses por pérdida temprana de piezas dentarias y niveles anormalmente bajos de fosfatasa alcalina, sin signos de raquitismo ni deformidades óseas. Durante su seguimiento, hasta los 13 años, presentó síntomas compatibles con HP infantil leve, como cansancio al caminar, incoordinación en la marcha y dolor en miembros inferiores que aumentaban con la actividad física. Ante la aparición de edema bimaleolar y poca respuesta al tratamiento con calcitonina y antiinflamatorios, se descartaron patologías infecciosas o reumáticas o ambas y se diagnosticó, por biopsia de tibia y peroné, periostitis sin detección de cristales de pirofosfato. Los controles radiológicos durante su evolución mostraron ensanchamiento metafisario en muñeca, falta de remodelado de metacarpianos, hojaldrado perióstico en tibia y peroné e hipomineralización en metáfisis tibiales, con "lenguas radiolúcidas" características de HP. Como conclusión, la hipofosfatasia debe considerarse como una entidad clínica para descartar en niños que presentan pérdida temprana de dientes. La presencia de este cuadro clínico es en general suficiente para realizar el diagnóstico de HP de la niñez. (AU)

Hypophosphatasia (HP) is a congenital disease, caused by mutations with loss of function in the gene ALPL that encodes the non-specific tissue isoenzyme of alkaline phosphatase (TNSALP). Its clinical expression displays considerable variability, from cases of intrauterine death due to severe alteration of bone mineralization, to cases with only early loss of teeth. We report the case of a male, diagnosed as odontohypophosphatasia at 30 months of age due to early loss of teeth and abnormally low levels of alkaline phosphatase, without signs of rickets or bone deformities. During follow-up, up to 13 years of age, he presented symptoms consistent with mild infantile HP such as tiredness when walking, lack of gait coordination, and pain in lower limbs, especially after physical activity. Due to the appearance of bimalleolar edema and poor response to treatment with calcitonin and anti-inflammatory drugs, infectious and / or rheumatic pathologies were ruled out. Periostitis without pyrophosphate crystal detection was diagnosed by tibial and fibular biopsy. Radiological controls during follow up showed metaphyseal wrist enlargement, lack of remodeling of metacarpals, periosteal flaking in the tibia and fibula and hypomineralization in the tibial metaphysis, with "radiolucent tongues"; characteristic of HP. In conclusion, hypophosphatasia should be considered as a clinical entity in children who present early loss of teeth. The presentation of this clinical case is generally sufficient to make the diagnosis of childhood HP. (AU)

Alfacalcidol Increases the Therapeutic Efficacy of Ibandronate on Bone Mineral Density in Japanese Women with Primary Osteoporosis.

Bisphosphonates (BPs) increase bone mineral density (BMD) through the inhibition of osteoclast activity. Among BPs, ibandronate (IBN) is a strong inhibitor of bone resorption. However, the effects of a vitamin D analogue, alfacalcidol (ALF), on IBN treatment for osteoporosis is unknown. Fifty-three treatment-naïve post-menopausal women with primary osteoporosis were recruited and divided into IBN-treatment group (IBN group) and IBN with ALF group (IBN/ALF group). IBN (1.0 mg) was intravenously injected once a month, with or without oral ALF (1.0 µg/day). Ultimately, 19 subjects in IBN group and 26 in IBN/ALF group were analyzed. Bone turnover markers were examined at 4, 6, 12, and 18 months, and BMD was measured at 6, 12, and 18 months. Compared with pre-treatment, bone turnover markers significantly decreased in both groups after 4 months. The levels of serum N-terminal propeptide of type-1 procollagen and tartrate-resistant acid phosphatase-5b, and urinary N-terminal telopeptide of type-I collagen were significantly lower in IBN/ALF group than those in IBN group at 12 months. Lumbar 1-4 (L)-BMD significantly increased from 6 months in IBN/ALF group and at 18 months in IBN group. L-BMD was significantly higher in IBN/ALF group (6.6% increase) than in IBN group (3.4%) at 18 months. Total hip (H)-BMD significantly increased from 6 months in IBN/ALF group and tended to improve in IBN group. H-BMD was significantly higher in IBN/ALF group (4.8%) than in IBN group (3.2%) at 18 months. In conclusion, treatment with ALF in combination with IBN improves BMD in post-menopausal women with osteoporosis.

Comparison of Bone Mineral Density in Lumbar Spine and Fracture Rate among Eight Drugs in Treatments of Osteoporosis in Men: A Network Meta-Analysis.

CONTEXT: The preferred treatment for osteoporosis in men is debated, and pairwise meta-analysis cannot obtain hierarchies of these treatments. OBJECTIVE: The objective of this study was to integrate the evidence and provide hierarchies of eight drugs based on their effect on the bone mineral density in the lumbar spine (BMD in LS) and the fracture rate. DATA SOURCES: Eligible studies were identified by searching Amed, British Nursing Index, EMBASE, PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, SIGLE, the National Technical Information Service, the National Research Register (UK), and the Current Controlled Trials databases. STUDY SELECTION: RCTs or quasi-RCTs reporting at least two drugs (two active drugs or one active drug and a placebo) used to treat osteoporosis in men were selected by two authors. DATA EXTRACTION: Two authors independently extracted the data. DATA SYNTHESIS: Thirteen studies involving 3647 patients were included. Compared with placebo therapy, zoledronate (SMDs 13.48, 95% credible intervals 11.88-15.08) yielded the most significant effect on increasing the BMD in LS, followed by alendronate (11.04, 9.68-12.41), teriparatide (20mcg) + risedronate (10.98, 8.55-13.48), risedronate (10.33, 8.68-12.01), teriparatide (20mcg) (9.33, 6.87-11.76), strontium ranelate (8.88, 7.51-10.24), ibandronate (5.49, 3.82-7.16), parathyroid hormone (1-84) (4.89, 3.12-6.62) and alfacalcidol (3.42, 1.7-5.2). Placebo therapy had a significantly higher fracture rate in contrast to risedronate (OR 2.51, 95% CrI 1.23-4.24) or zoledronate (2.92, 1.29-5.62) or teriparatide (20mcg) (4.04, 1.36-8.49) or teriparatide (40mcg) (3.5, 1.14-8.34). Zoledronate ranked first for increasing the BMD in LS, and teriparatide (20mg) was ranked first for decreasing the fracture rate. CONCLUSIONS: Zoledronate might be the best choice to increase the BMD in LS and teriparatide (20mg) might lead to the lowest fracture rate.

Vitamin D for the treatment of chronic painful conditions in adults.

BACKGROUND: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 1, 2010) on 'Vitamin D for the treatment of chronic painful conditions in adults'.Vitamin D is produced in the skin after exposure to sunlight and can be obtained through food. Vitamin D deficiency has been linked with a range of conditions, including chronic pain. Observational and circumstantial evidence suggests that there may be a role for vitamin D deficiency in the aetiology of chronic painful conditions. OBJECTIVES: To assess the efficacy and safety of vitamin D supplementation in chronic painful conditions when tested against placebo or against active comparators. SEARCH METHODS: For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE to February 2015. This was supplemented by searching the reference lists of retrieved articles, reviews in the field, and online trial registries. SELECTION CRITERIA: We included studies if they were randomised double-blind trials of vitamin D supplementation compared with placebo or with active comparators for the treatment of chronic painful conditions in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies for inclusion, assessed methodological quality, and extracted data. We did not undertake pooled analysis due to the heterogeneity of the data. Primary outcomes of interest were pain responder outcomes, and secondary outcomes were treatment group average pain outcomes and adverse events. MAIN RESULTS: We included six new studies (517 participants) in this review update, bringing the total of included studies to 10 (811 participants). The studies were heterogeneous with regard to study quality, the chronic painful conditions that were investigated, the dose of vitamin D given, co-interventions, and the outcome measures reported. Only two studies reported responder pain outcomes; the other studies reported treatment group average outcomes only. Overall, there was no consistent pattern that vitamin D treatment was associated with greater efficacy than placebo in any chronic painful condition (low quality evidence). Adverse events and withdrawals were comparatively infrequent, with no consistent difference between vitamin D and placebo (good quality evidence). AUTHORS' CONCLUSIONS: The evidence addressing the use of vitamin D for chronic pain now contains more than twice as many studies and participants than were included in the original version of this review. Based on this evidence, a large beneficial effect of vitamin D across different chronic painful conditions is unlikely. Whether vitamin D can have beneficial effects in specific chronic painful conditions needs further investigation.

Anticonvulsant treatment associated with intractable hypocalcaemia in a female child with hypoparathyroidism.

BACKGROUND: We report the case of a female infant with hypoparathyroidism due to an activating mutation in the calcium-sensing receptor gene. CASE REPORT: The child presented in the neonatal period with clinical seizures associated with severe hypocalcaemia, hyperphosphataemia, low parathyroid hormone levels and elevated urine calcium:creatinine ratios. She required intravenous calcium and phenobarbitone initially, and then oral 1-alfacalcidol (1-AC) and phenobarbitone were started. The patient had intractable hypocalcaemia in the first 5 months of life despite escalating doses of 1-AC. When the phenobarbitone was stopped at 5 months of age she was admitted soon after with symptomatic hypercalcaemia. We postulate that the phenobarbitone increased the metabolism of 1-AC and thus she needed large doses of 1-AC to treat hypocalcaemia until the phenobarbitone was stopped. Her parents had no biochemical abnormalities on testing. RESULTS: Molecular genetic analysis confirmed that our patient had a de novo missense variant, c.682G>A (p.Glu228Lys) in exon 4 of the calcium-sensing receptor. CONCLUSION: This case report highlights the importance that clinicians caring for children on vitamin D and its analogues are aware of the interaction with phenobarbitone, which can result in symptomatic hypocalcaemia. 1-AC should be stored at 2-8°C, otherwise it will be rendered inactive.

[Medical treatment of children with hypophosphataemic rickets]. / Medicinsk behandling af hypofosfatæmisk rakitis hos børn.

Hypophosphataemic rickets is a rare, genetic disorder resulting in defect bone mineralisation and rickets. The current medical treatment consists of phosphate supplementation and alfacalcidol, but side effects such as secondary hyperparat-hyroidism and nephrocalcinosis are common. This treatment regimen often fails to prevent bone deformity and reduced final height. The rarity and complexity of these diseases call for centralised specialist care and international collaboration. Future medical treatment may be improved by addition of new promising experimental treatments.

[Symptoms of severe calciphylaxis in a girl with X-linked hypophosphataemia].

X-linked hypophosphataemia (XLH) is the most common form of hereditary rickets. We present a case report of a girl who was diagnosed with XLH. She was treated with activated vitamin D and phosphate and received several correctives surgical procedures. After a knee surgery, complicated with osteomyelitis, she presented with symptoms of severe calciphylaxis with calcification of several organ systems. Medical therapy was paused and systemic inflammation was treated with steroids and loop diuretics. This case report underlines the necessity of careful dosage of vitamin D and pausing of medical therapy after surgical procedures in patients with XLH.

[Experience with active vitamin D metabolites in phosphorus-calcium metabolic disorders in patients with predialysis chronic kidney disease].

AIM: To evaluate the efficacy and safety of alfacalcidol and paracalcitol used to correct impaired phosphorus-calcium metabolism (PCM) in patients with predialysis chronic kidney disease (CKD). SUBJECTS AND METHODS: Examinations were made in 128 patients with Stages III-V CKD, including 89 (69.5%) patients with chronic glomerulonephritis, 30 (23.4%) with chronic tubulointerstitial nephritis, and 9 (7.1%) with hypertensive nephrosclerosis. Impaired PCM was detected in 90 (70.3%) of the examined patients. According to the pattern of the previous therapy, all the 90 CKD patients with PCM disorders were divided into 3 groups: 1) 32 patients with Stages IIIB-V CKD who had taken oral alfacalcidol 0.25 microg/day; 2) 28 patients with Stages IIIB-V CKD who had used oral paricalcitol 1 microg/day; 3) 30 patients with Stages IIIB-V CKD who had not received, as self- motivated, active vitamin D metabolites at the predialysis stage. RESULTS: Alfacalcidol and paricalcitol were quite satisfactorily tolerated by the patients. After 3 months of initiation of the use of these agents, Groups 1 and 2 patients with predialysis CKD and baseline elevated blood intact parathyroid hormone (iPTH) levels could not only achieve, but also maintain target blood iPTH levels. In the patients taking paricalcitol, the urinary protein level decreased more promptly; moreover, by the end of month 6 the reduction in blood pressure (BP) was more significant than in those using alfacalcidol (p < 0.05). Comparison of the effects of angiotensin-converting enzyme inhibitors in combination with alfacalcidol or paricalcitol on BP changes and left ventricular mass index indicated that the most pronounced positive changes occurred when angiotensin-converting enzyme inhibitors were used in combination with paricalcitol. CONCLUSION: The use of paricalcitol in predialysis CKD with PTH hyperproduction results in not only normalization of the levels of both PTH and osseous isoenzyme of alkaline phosphatase, but also in significantly reduced daily proteinuria and regression of left ventricular hypertrophy and chronic heart failure.

Active vitamin D analogs, maxacalcitol and alfacalcidol, as maintenance therapy for mild secondary hyperparathyroidism in hemodialysis patients - a randomized study.

BACKGROUND: The present randomized study was designed to compare the efficacy between two active vitamin D analogs, alfacalcidol (ACD) and maxacalcitol (OCT), for the management of mild secondary hyperparathyroidism (SHPT) in dialysis patients. METHODS: SHPT in all 32 patients analyzed in the study was initially treated with OCT. Once patients' intact PTH levels decreased to the target range of 150 - 180 pg/mL, they were randomized either to switch to ACD at 0.5 µg/day (n = 14), or to remain on an effectively unchanged dose of OCT (n = 13). Phosphate, calcium, and intact PTH levels were measured every 2 weeks for 12 weeks and vitamin D doses were changed according to target ranges of phosphate (3.5 - 6.0 mg/dL), calcium (albuminadjusted calcium: 8.4 - 10.0 mg/dL), and intact parathyroid hormone (60 - 180 pg/mL). Achievement rates of the target ranges of the parameters were estimated. RESULTS: Baseline calcium levels in the OCT group were significantly higher than in the ACD group. Changes in achievement rates of target ranges of intact PTH and calcium during the study did not differ significantly between the vitamin D drugs. Changes in calcium levels in the OCT and ACD groups were similar during the study. Achievement rates of the target range of phosphate in both groups were also similar until 8 weeks, although the rate in the OCT group declined at 10 weeks. CONCLUSIONS: The efficacy and safety of OCT for the treatment of mild SHPT are similar to those of ACD in hemodialysis patients.

Association between vitamin D receptor activator and the risk of infection-related hospitalizations among incident hemodialysis patients: a nested case-control study.

BACKGROUND: Patients suffering from chronic kidney disease are at greater risk of developing infection than the normal population, and infections are the second cause of mortality after cardiovascular complications in this population. Some reports suggest that the intake of active vitamin D might be beneficial to prevent infections. Therefore, we aimed to determine if the oral intake of vitamin D receptor activator (VDRA) is associated with a lower risk of infection-related hospitalization (IRH) among incident chronic hemodialysis patients. METHODS: We conducted a nested case-control study in a cohort of 4933 patients initiating chronic hemodialysis between 1 January 2001 and 31 December 2007 in Quebec, Canada, using administrative databases. We identified cases of hospital admission indicating an infection as main diagnosis on the hospital's discharge sheet. Up to 10 controls were randomly selected for each case. Association between oral VDRA use and risk of IRH was estimated using conditional logistic regression. RESULTS: We identified 1136 cases of IRH and 10396 controls during the study period. The intake of VDRA was not associated with the risk of being hospitalized due to an infection (odds ratio [OR], 1.07; 95% confidence interval [CI], 0.95-1.20). Using the prior 6-month cumulative dose of VDRA, we also found that a cumulative VDRA dose of less than 45 mcg (OR, 1.05; 95%CI, 0.92-1.19) or greater than 45 mcg (OR, 1.15; 95%CI, 0.96-1.36) was not associated with the IRH risk. CONCLUSIONS: The oral intake of VDRA was not associated with the risk of IRH in incident hemodialysis patients.

Clinical uses of 1-alpha-hydroxycholecalciferol.

Alfacalcidol is a widely used vitamin D compound, especially in clinical nephrology because it does not require enzymatic activation by the kidneys. For that reason it has been used for decades to treat abnormalities in bone and mineral balance that arise in chronic kidney disease. In this review an overview is provided of available experimental and clinical data that form the basis of its widespread use. Supported by studies on cell lines and animal models, clinical studies have firmly established beneficial effects of alfacalcidol on chronic-kidney disease (CKD-) related bone disease and secondary hyperparathyroidism. Its effects on muscle structure and function are not unambiguous. Neither experimental nor clinical data suggest beneficial effects of alfacalcidol on indicators of cardiovascular disease, including cardiovascular calcification, left ventricular mass function or hypertension. Suggestions of improved mortality in dialysis patients treated with alfacalcidol are based on observational cohort analyses. Integrating all available data leads the conclusion that alfacalcidol is a justifiable compound to prescribe to CKD patients with established bone disease or hyperparathyroidism. Monitoring of calcium and phosphorus levels after its initiation is required and dose adaptations should be made accordingly.

Intravenous alfacalcidol once versus twice or thrice weekly in hemodialysis patients.

Secondary hyperparathyroidism remains a serious problem in hemodialysis patients. The use of vitamin D analogs still constitutes a basis for its treatment. This study was carried out to evaluate the efficacy of intravenous administration of alfacalcidol once versus twice or thrice weekly in hemodialysis patients with secondary hyperparathyroidism. Twenty-nine end-stage renal disease patients maintained on hemodialysis for more than one year were included in this prospective study after signing the consent. These patients with secondary hyperparathyroidism had been on intravenous alfacalcidol twice or thrice per week and were followed up to 4 months (stage 1). Then they were shifted to intravenous alfacalcidol once weekly starting with the last total weekly intravenous dose for another 4 months (stage 2). The dose of alfacalcidol was adjusted according to intact parathyroid hormone, serum calcium and phosphorus levels, and calcium-phosphorus product. Intact parathyroid hormone, calcium, phosphorus, calcium-phosphorus product were measured monthly. Parathyroid ultrasound was done as a baseline and then repeated at the end of stage 1 and stage 2. The intact parathyroid hormone was reduced from 49.72 ± 2.72 pmol/L (mean ± standard error of the mean [SEM] during stage 1 to 42.13 ± 2.15 pmol/L during stage 2 (P = 0.005). Dose of alfacalcidol was reduced from 18.80 ± 1.15 µg/month (mean ± SEM) in stage 1 to 15.18 ± 1.27 µg/month in stage 2 (P = 0.008), and consequently the cost of alfacalcidol was reduced from 21.05 ± 1.25 US$/month (mean ± SEM) during stage 1 to 16.87 ± 1.40 US$/month during stage 2 (P = 0.008). Although the phosphorus level increased from 1.56 ± 0.36 mmol/L (mean ± SD) in stage 1 to 1.70 ± 0.46 mmol/ L in stage 2 (P = 0.003), and calcium-phosphorus product increased from 3.48 ± 0.82 mmol(2)/L(2) (mean ± SD) in stage 1 to 3.76 ± 1.00 mmol(2) /L(2) in stage 2 (P = 0.017), they remained in the target levels recommended by the Kidney Disease Outcomes Quality Initiative guidelines. No serious effects were observed during stage 1 and stage 2, respectively. Intravenous alfacalcidol once weekly is effective, safe and less costly in suppressing intact parathyroid hormone compared to twice or thrice weekly administration in chronic hemodialysis patients.

Early bioprosthetic valve calcification with alfacalcidol supplementation.

We report a case of early bioprosthetic valve calcification in a 76 year-old woman who had received supplementation with alfacalcidol, an analogue of vitamin D, for 3 years after her initial valve replacement. She underwent aortic valve replacement at the age of 71 and subsequently complained of shortness of breath. Ultrasonic cardiography revealed severe aortic stenosis and we performed a second aortic valve replacement with a bioprosthesis. Histopathologic and x-ray examination showed calcification on the explanted valve. She had not presented with any known risk for early bioprosthetic calcification, suggesting that vitamin D supplementation may accelerate calcification of bioprosthetic valves.