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Objective: To quantitatively assess all dosage forms of three active vitamin D and its analogs, namely, calcitriol, alfacalcidol, and eldecalcitol, to provide a basis for the selection of active vitamin D and its analogs in hospitals. Methods: In this study, three active vitamin D and its analogs were evaluated by quantitative scoring in five dimensions, including pharmaceutical properties (28 points), efficacy (27 points), safety (25 points), economy (10 points), and other attributes (10 points). Results: The final scores of quantitative assessment for the selection of alfacalcidol soft capsules, calcitriol soft capsules I, calcitriol soft capsules II, alfacalcidol tablets, alfacalcidol capsules, alfacalcidol oral drops, calcitriol injection, and eldecalcitol soft capsules were 73.17, 72.06, 71.52, 71.29, 69.62, 68.86, 65.60, 64.05 points. Conclusion: Based on the scoring results, alfacalcidol soft capsules, calcitriol soft capsules I, calcitriol soft capsules II, alfacalcidol tablets can be entered into the medication list of medical institutions as strongly recommended drugs. This study offers guidance on selecting and using active vitamin D and its analogs in hospitals, with consideration for the patient's needs.
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Hidroxicolecalciferóis , Osteoporose , Vitamina D , Humanos , Osteoporose/tratamento farmacológico , Vitamina D/administração & dosagem , Vitamina D/análogos & derivados , Hidroxicolecalciferóis/administração & dosagem , Hidroxicolecalciferóis/uso terapêutico , Avaliação da Tecnologia Biomédica , Conservadores da Densidade Óssea/administração & dosagem , China , Calcitriol/análogos & derivados , Calcitriol/administração & dosagem , CápsulasRESUMO
BACKGROUND: Debate continues as to the optimum hemodialysis (HD) dialysate calcium concentration. Although current guidelines advocate 1.25-1.5 mmol/L, some investigators have suggested these may cause calcium gains. As such we investigated whether using dialysate calcium of 1.25 mmol/L risked calcium gains, and whether there were differences between hemodiafiltration and high flux HD. METHODS: We continuously collect an aliquot of effluent dialysate during dialysis sessions, and calculated dialysis calcium mass balance by the difference between the amount of calcium delivered as fresh dialysate and that lost in effluent dialysate. RESULTS: We studied 106 stable outpatients, 64% male, mean age 64.4 ± 16.2 years, median dialysis vintage 32 (22-60) months. Most sessions (69%) used a 1.0 mmol/L calcium dialysate, with a median sessional loss of 13.7 (11.5-17.1) mmol, whereas using 1.25 mmol/L the median loss was 7.4 (4.9-10.1) mmol, but with 6.9% had a positive balance (p = 0.031 vs dialysate calcium 1.0 mmol/L). Most patients (85.8%) were treated by hemodiafiltration, but there was no difference in sessional losses (11.7 (8.4-15.8) vs 13.5 (8.1-16.8)) with high flux HD. Dialysis sessional calcium balance was associated with the use of lower dialysate calcium concentration (ß -19.5, 95% confidence limits (95%CL) -27.7 to -11.3, p < 0.001), and sessional duration (ß 0.07 (95% CL) 0.03-012, p = 0.002). CONCLUSION: Ideally, the choice of dialysate calcium should be individualized, but clinicians should be aware, that even when using a dialysate calcium of 1.25 mmol/L, some patients are at risk of a calcium gain during hemodiafiltration and high-flux hemodialysis.
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Cálcio , Soluções para Diálise , Hemodiafiltração , Diálise Renal , Humanos , Masculino , Pessoa de Meia-Idade , Hemodiafiltração/métodos , Feminino , Cálcio/análise , Idoso , Diálise Renal/métodos , Diálise Renal/efeitos adversos , Soluções para Diálise/química , Idoso de 80 Anos ou mais , Falência Renal Crônica/terapia , Soluções para Hemodiálise/químicaRESUMO
OBJECTIVE: To investigate the effectiveness of Alfacalcidol combined with Calcitonin in the treatment of osteoporosis and its influence on the degree of pain, bone metabolism indexes, bone mineral density and inflammatory factor levels. METHODS: In this retrospective study, 110 patients with osteoporosis treated in The Second Affiliated Hospital of Shandong First Medical University from January 2019 to June 2021 were selected as the study subjects. According to different treatment methods, these patients were divided into an observation group and a control group with 55 cases in each group. Patients from the control group were treated with the alfacalcidol capsules alone, while those from the observation group were treated with the alfacalcidol capsules combined with intramuscular calcitonin injection. Patients in both groups were treated for 6 months continuously. The treatment effect, visual analogue scale (VAS) score and Oswestry disability index (ODI), bone mineral density (BMD), serum markers levels such as calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase-5b (TRACP-5b), insulin-like growth factor (IGF-1), type I procollagen amino terminal propeptide (PINP) and ß-collagen special sequence (ß-Crosslaps), the levels of inflammatory factor including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), quality Life Questionnaire Core 30 (QLQ-C30) scores and incidences of adverse reactions were evaluated and compared between the two groups. RESULTS: The effective rate of patients in the observation group was 90.91%, which was significantly higher than 74.54% in the control group (P<0.05). There was no significant difference in the term of VAS score, ODI score, serum markers levels, bone mineral density, inflammatory levels, QLQ-C30 before treatment between the two groups. Compared with the control group, the post-treatment VAS score, ODI score, the levels of IL-6, TNF-α, TRACP-5b, PINP and ß-Crosslaps in the observation group were obviously lower, while the post-treatment QLQ-C30, bone mineral density, Ca, P, ALP, IGF-1 levels were significantly higher (all P<0.05). No statistical differences were found in the incidences of adverse reactions between the two groups (P>0.05). CONCLUSION: The combination of Alfacalcidol combined with Calcitonin is effective in the treatment of osteoporosis patients, which can effectively improve the levels of bone metabolism indexes and bone mineral density, alleviate the symptoms, enhance the life quality and reduce the levels of inflammation. Therefore, it is worth promoting.
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BACKGROUND: Vitamin D supplementation for infectious diseases has been discussed, but its role in COVID-19 is unclear. Therefore, this study examined the clinical outcomes of COVID-19 pneumonia patients who received vitamin D supplementation. METHODS: This prospective, open-label, randomized controlled trial was conducted in a university hospital between July 2020 and March 2022. The inclusion criteria were patients aged ≥ 18 years with COVID-19 pneumonia patients. The patients were randomized into two groups: an intervention group receiving vitamin D supplementation (alfacalcidol, two mcg orally daily) until discharge and a control group. The clinical outcomes were pneumonia treatment duration, length of hospital stay, and change in pneumonia severity index between enrollment and discharge. Subgroup analysis was conducted for supplemental oxygen use, high-dose corticosteroid administration, evidence of lymphopenia, C-reactive protein concentration, and total serum vitamin D concentration. Adverse events were monitored. RESULTS: Two hundred ninety-four patients were recruited (147 per group). The two groups did not differ in pneumonia treatment duration to discharge (p = 0.788) or length of hospital stay (p = 0.614). The reduction in the pneumonia severity index between enrollment and discharge was more significant in the intervention group (p = 0.007); a significant decrease was also observed among patients who had C-reactive protein > 30 mg/L (p < 0.001). No adverse reactions were recorded. CONCLUSIONS: Adding active vitamin D to standard treatment may benefit COVID-19 pneumonia patients who require supplemental oxygen or high-dose corticosteroid therapy or who have high C-reactive protein concentrations (> 30 mg/L) upon treatment initiation. TRIAL REGISTRATION: Thai Clinical Trials Registry TCTR20210906005 (retrospectively registered, 6 September 2021).
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COVID-19 , Humanos , SARS-CoV-2 , Estudos Prospectivos , Proteína C-Reativa , Vitamina D/uso terapêutico , Suplementos Nutricionais , Corticosteroides/uso terapêutico , OxigênioRESUMO
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.
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Calcitriol , Endocrinologia , Humanos , Calcitriol/efeitos adversos , Hidroxicolecalciferóis/efeitos adversos , Resultado do TratamentoRESUMO
Only a few studies evaluating the metabolism of vitamin D in patients with hypoparathyroidism (HypoPT) have been performed thus far, and, in particular, they mainly investigated the process of vitamin D activation (specifically, 1α-hydroxylation). This study, therefore, aimed to evaluate the extended spectrum of vitamin D metabolites in patients with HypoPT compared to healthy individuals. We examined 38 adult patients with chronic HypoPT in comparison to 38 healthy adults. The assessment included biochemical parameters (total calcium, albumin, phosphorus, creatinine, and magnesium), parathyroid hormone (PTH), and vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3, and 24,25(OH)2D3) in serum. Our data show that an adequate level of 25(OH)D3 (median 35.3 (29.6; 42.0) ng/mL) is achieved with standard doses of cholecalciferol (median 2000 (2000; 2500) IU per day) in HypoPT patients. They also presented with supraphysiological levels of 1,25(OH)2D3 (median 71 (47; 96) vs. 40 (34; 59) pg/mL, p < 0.001) and the increased production of inactive metabolite (median 24,25(OH)2D3 3.8 (3.0; 5.1) vs. 1.9 (1.3; 2.7) ng/mL, p < 0.001; median 25(OH)D3/24,25(OH)2D3 ratio 8.9 (7.6; 11.1) vs. 13.5 (11.1; 17.0), p < 0.001) as compared to the control group. This might be a consequence of the therapy received (treatment with activated vitamin D) and the pathophysiology of the disease (lack of PTH). The abnormality of vitamin D metabolism does not seem to interfere with the achievement of hypoparathyroidism compensation.
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The objective was to test the hypothesis that supplementation of diets for gestating sows with 25-hydroxycholecalciferol (25-OH-D3) or 1-hydroxycholecalciferol (1-OH-D3) affects serum biomarkers for bone and increases Ca and P balance and the apparent total tract digestibility (ATTD) of gross energy (GE), and the concentrations of digestible energy (DE) and metabolizable energy (ME) in diets without or with microbial phytase. Sixty multiparous sows were allotted to 1 of 6 diets. Diets were formulated using a 3â ×â 2 factorial with 3 inclusions of supplemental vitamin D metabolite (no metabolite, 25-OH-D3, or 1-OH-D3) and 2 inclusion levels of microbial phytase (0 or 1,000 units). Sows were housed individually in metabolism crates and feces and urine were collected quantitatively. Results indicated that there was no difference in the ATTD of dry matter (DM) and GE and concentration of DE among the 3 diets containing microbial phytase, but the ATTD of DM and GE and concentration of DE was greater (Pâ <â 0.05) in diets containing 1-OH-D3 compared with the diet without a vitamin D metabolite if phytase was not used (interaction; Pâ <â 0.05). In diets without microbial phytase, ME was greater in diets containing either one of the 2 vitamin D metabolites than in the diet without a vitamin D metabolite, but among diets with microbial phytase, the ME of the 1-OH-D3 diet was less than of the 25-OH-D3 diet (interaction; Pâ <â 0.05). No effect of microbial phytase on concentrations of DE and ME was observed. There was no interaction between supplementation of microbial phytase and vitamin D metabolites for Ca and P balances, and regardless of metabolite supplementation, use of microbial phytase increased (Pâ <â 0.05) the ATTD and retention of Ca and P. Regardless of dietary phytase, the ATTD and retention of Ca and P increased (Pâ <â 0.05) for sows fed a diet containing one of the vitamin D metabolites compared with sows fed the diet without a vitamin D metabolite. Serum biomarkers for bone resorption or bone tissue synthesis were not affected by experimental diets. In conclusion, the ATTD of DM and GE, concentrations of DE and ME, and Ca and P balance in phytase-free diets fed to sows in late gestation were increased by supplementation with 1-OH-D3 or 25-OH-D3, but no differences between the 2 vitamin D metabolites were observed. Supplementation of diets with microbial phytase increased Ca and P balance, but did not affect DE and ME of diets.
The role of vitamin D is to increase absorption of calcium and phosphorus in the gastrointestinal tract and maintain serum concentrations of calcium, but dietary vitamin D needs to be converted to an active form by 2-hydroxylation steps that take place in the liver and the kidneys. The conversion efficiency to active vitamin D may be increased if pre-hydroxylated metabolites rather than vitamin D are provided, which also increases calcium and phosphorus utilization. In a previous experiment it was also demonstrated that a vitamin D metabolite increases energy absorption in gestating sows. It is possible that use of a vitamin D metabolite and phytase have additive effects and the hypothesis, therefore, was that supplementation of a vitamin D metabolite increases calcium and phosphorus balance and energy digestibility in diets fed to gestating sows without or with microbial phytase. Results indicated that in diets without phytase, the 2 vitamin D metabolites increased energy concentration in diets by increasing apparent energy digestibility. There was no interaction between supplementation of phytase and vitamin D metabolites for calcium and phosphorus balances. Use of phytase and vitamin D metabolites increased calcium and phosphorus digestibility and retention.
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6-Fitase , Fósforo na Dieta , Gravidez , Animais , Feminino , 6-Fitase/farmacologia , Cálcio/metabolismo , Calcifediol/farmacologia , Fósforo/metabolismo , Fósforo na Dieta/metabolismo , Digestão , Ração Animal/análise , Trato Gastrointestinal/metabolismo , Cálcio da Dieta/metabolismo , Dieta/veterinária , Biomarcadores/metabolismo , Osso e Ossos/metabolismoRESUMO
PTH resistance is characterized by elevated parathyroid hormone (PTH) levels, hypocalcemia, hyperphosphatemia and it is classically associated with GNAS locus genetic or epigenetic defects. Inactivating PTH/PTHrP signaling disorders (iPPSD) define overlapping phenotypes based on their molecular etiology. iPPSD1 is associated with PTH1R variants and variable phenotypes including ossification anomalies and primary failure of tooth eruption but no endocrine disorder. Here we report on a 10-month-old child born from consanguineous parents, who presented with mild neurodevelopmental delay, seizures, enlarged fontanelles, round face, and bilateral clinodactyly. Hand x-rays showed diffuse delayed bone age, osteopenia, short metacarpal bones and cone-shaped distal phalanges. A diagnosis of PTH resistance was made on the basis of severe hypocalcemia, hyperphosphatemia, elevated PTH and normal vitamin D levels on blood sample. The patient was treated with calcium carbonate and alfacalcidol leading to rapid bio-clinical improvement. Follow-up revealed multiple agenesis of primary teeth and delayed teeth eruption, as well as Arnold-Chiari type 1 malformation requiring a ventriculoperitoneal shunt placement. GNAS gene analysis showed no pathogenic variation, but a likely pathogenic homozygous substitution c.723C>G p.(Asp241Glu) in PTH1R gene was found by trio-based whole exome sequencing. We studied the deleterious impact of the variant on the protein conformation with bioinformatics tools. In conclusion, our study reports for the first time PTH resistance in a child with a biallelic PTH1R mutation, extending thereby the clinical spectrum of iPPSD1 phenotypes.
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Hiperfosfatemia , Hipocalcemia , Pseudo-Hipoparatireoidismo , Humanos , Hipocalcemia/complicações , Hormônio Paratireóideo/metabolismo , Proteína Relacionada ao Hormônio Paratireóideo , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/genéticaRESUMO
BACKGROUND: This study evaluates the effects of active (1α-hydroxylated) vitamin D (AVD) therapy on hypercalcaemia in patients with non-dialysis chronic kidney disease (ND-CKD) and secondary hyperparathyroidism (SHPT). METHODS: A systematic search of the PubMed, Embase and Cochrane Library databases (up to 14 May 2020) was performed to identify randomized, placebo-controlled trials of single-agent, oral AVD therapies in adults with ND-CKD and SHPT. Only studies with ≥30 participants per arm and ≥6 weeks in duration were eligible. The outcome of interest was the number of subjects with an episode of hypercalcaemia. A meta-analysis of eligible studies was conducted using Comprehensive Meta-Analysis software (version 3.0). RESULTS: Six studies (five evaluating paricalcitol, one evaluating alfacalcidol) involving 799 patients were identified. Treatment durations ranged from 16 weeks to 2 years. The weekly doses of paricalcitol administered were 7 (three studies) and 14 µg (two studies); the weekly dose of alfacalcidol was 1.75-7.0 µg. Across all studies, rates of hypercalcaemia were 1.1-43.3% with AVD versus 0-3.4% with placebo. Meta-analysis of the six studies showed that AVD was associated with a 6.6-fold greater probability of hypercalcaemia versus placebo (odds ratio: 6.63, 95% confidence interval: 2.37, 18.55; P < 0.001). Two separate sensitivity analyses (one excluded a study identified as having a high risk of bias; the second excluded two studies that accounted for a large proportion of observed hypercalcaemia events) indicated the primary meta-analysis findings were robust. CONCLUSIONS: Compared with placebo, AVD significantly increased the risk of hypercalcaemia among ND-CKD patients with SHPT.
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OBJECTIVES: To study the effects of alfacalcidol on serum 25-(OH)D3 level, cellular immune function, and inflammatory factors in children with Henoch-Schönlein purpura (HSP). METHODS: A total of 200 children with HSP were prospectively enrolled from June 2018 to June 2020. According to the random number table method, they were divided into an observation group and a control group (n=100 each). The control group was treated with vitamin C, rutin tablets, dipyridamole, cimetidine, calcium supplements, and glucocorticoids. In addition to the treatment for the control group, the observation group received alfacalcidol capsules (0.25 µg/d) orally before bed for 4 weeks. The two groups were compared in terms of the level of 25-(OH)D3, the percentages of T lymphocyte subsets (CD3+, CD4+, and CD8+) and NK cells, and the levels of inflammatory factors, interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-21 (IL-21), and tumor necrosis factor-α (TNF-α), before treatment and after 4 weeks of treatment. The children were followed up for 6 months to determine the recurrence rate and the incidence of renal damage. RESULTS: After treatment, the observation group showed a significantly higher serum 25-(OH)D3 level, significantly higher percentages of CD3+T cells, CD4+T cells, and NK cells, and significantly lower levels of IL-6, IL-17, IL-21, and TNF-α compared with the control group (P<0.05). After 6 months of follow-up, the recurrence rate and the incidence of renal damage in the observation group were significantly lower than those in the control group (P<0.05). CONCLUSIONS: Alfacalcidol can increase the serum 25-(OH)D3 level, improve cellular immune function, decrease inflammatory factor levels, and reduce recurrence and renal damage in children with HSP.
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Vasculite por IgA , Criança , Humanos , Hidroxicolecalciferóis , Vasculite por IgA/tratamento farmacológico , Interleucina-6 , Estudos ProspectivosRESUMO
Objective: This single center cross-sectional study aims to investigate the association between secondary hyperparathyroidism and body composition in pediatric patients with moderate (stage 3) and advanced (stage 4-5) chronic kidney disease (CKD). Methods: 61 patients (median age: 13.4 years) were included. Body composition indices, including lean tissue index (LTI) and fat tissue index (FTI), were measured using multi-frequency bio-impedance spectroscopy. Muscle wasting was defined as LTI adjusted to height-age (HA) z-score < -1.65 SD and high adiposity as FTI z-score > 1.65 SD. Serum mineral metabolism parameters, including serum intact parathormone (iPTH), calcium, phosphorus and 25-hydroxyvitamin D, as well as serum leptin were measured in each patient. In advanced CKD patients, the mean values of serum mineral laboratory parameters of the 6 months prior to body composition assessment were recorded, and alfacalcidol index, defined as weekly alfacalcidol dose (mcg/week) per pg/ml of iPTH × 1,000, was calculated. Results: In moderate CKD (31 patients), high iPTH (>90 ng/ml) was observed in 10 (32.3%) patients and was associated with higher FTI z-score (p = 0.022). Moreover, serum iPTH was negatively correlated to LTI HA z-score (rs = -0.486, p = 0.006), and positively correlated to serum leptin levels (rs = 0.369, p = 0.041). The positive correlation between FTI z-score and iPTH (rs = 0.393, p = 0.039) lost significance after adjustment for serum leptin. iPTH was positively associated with high adiposity (12 patients, 38.7%) after adjustment for the other mineral metabolism parameters (OR 1.023, 95% CI 1.002-1.045, p = 0.028). In advanced CKD (30 patients), no significant correlation was observed between iPTH and body composition indices and serum leptin levels. Eleven (36.7%) patients with muscle wasting presented lower alfacalcidol index (p = 0.017). Alfacalcidol index ≤ 24 was strongly associated with muscle wasting after adjustment for CKD stage and other mineral metabolism parameters (OR 7.226, 95% CI 1.150-45.384, p = 0.035). Conclusion: Secondary hyperparathyroidism is associated with high adiposity in moderate but not in advanced CKD, with leptin acting as a potential contributive factor. In advanced CKD, targeting higher alfacalcidol weekly dose per each unit of serum PTH seems beneficial for preventing muscle wasting.
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INTRODUCTION: In our clinical experience, need for doses of active vitamin D and calcium supplements changes during the period following a diagnosis of postsurgical hypoparathyroidism (HypoPT), but only sparse data are available. In the present study, we aimed to investigate the magnitude of changes in need for activated vitamin D (alfacalcidol) and calcium supplements during initiation of therapy as well as time to be expected until a stable phase was achieved. Furthermore, we determined the frequency of (unexpected) episodes of hypo- and hypercalcaemia after reaching a steady state for alfacalcidol and calcium. METHODS: Retrospective study of twenty-four patients with chronic postsurgical HypoPT (>6 months) diagnosed from 2016 to 2018. Data were extracted from medical records on doses of alfacalcidol and calcium as well as ionized plasma calcium levels (P-Ca2+) from time of diagnosis and until 86 weeks after surgery. RESULTS: Patients were treated with alfacalcidol and calcium in order to maintain a stable concentration of P-Ca2+. Our data demonstrated a great variation in treatment needs until 11 weeks after surgery, where the mean doses of alfacalcidol stabilize, while calcium doses stabilized a bit earlier. After the stable phase had emerged, 21 out of 24 patients continued to have one or more episodes of spontaneous hypo- or hypercalcaemia. CONCLUSIONS: Patients with chronic HypoPT attain a steady state for alfacalcidol 11 weeks after the diagnosis. Continuous monitoring of P-Ca2+ is of continued importance after reaching steady state due to a high frequency of spontaneous hypo- or hypercalcaemia.
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Hipoparatireoidismo , Cálcio da Dieta/uso terapêutico , Humanos , Hipoparatireoidismo/tratamento farmacológico , Hipoparatireoidismo/etiologia , Estudos Retrospectivos , Vitamina D/uso terapêutico , Vitaminas/uso terapêuticoRESUMO
OBJECTIVES: To compare the effect of eldecalcitol and alfacalcidol on skeletal microstructure by high-resolution peripheral QCT (HR-pQCT). METHODS: This was a substudy of a randomized, double-blind, active comparator trial. Five female osteoporotic patients with 1-year 0.75 µg/day eldecalcitol and 5 with 1-year 1.0 µg/day alfacalcidol completed HR-pQCT scans before and after treatment were enrolled. RESULTS: Total vBMD [1.67 ± 1.06% (mean ± SD), P = 0.043 versus baseline] and trabecular vBMD (2.91 ± 1.72%, P = 0.043) at the radius increased in eldecalcitol group, while total, trabecular, and cortical vBMD tended to decrease in alfacalcidol group, with a significant reduction in cortical vBMD at the tibia (0.88 ± 0.62%, P = 0.043). Cortical area (1.82 ± 1.92%, P = 0.043) at the radius and thickness (0.87 ± 1.12%, P = 0.043) at the tibia increased in eldecalcitol group, while these parameters decreased with alfacalcidol at the tibia (1.77 ± 1.72%, P = 0.043 for cortical area; 1.40 ± 2.14%, P = 0.042 for cortical thickness). Trabecular thickness at the radius (1.97 ± 1.93%, P = 0.042) and number at the tibia (3.09 ± 3.04%, P = 0.043) increased by eldecalcitol but did not increase by alfacalcidol. Trabecular separation decreased by eldecalcitol (2.22 ± 2.43%, P = 0.043) but tended to increase by alfacalcidol at the tibia. CONCLUSIONS: Eldecalcitol has the greater potential to improve cortical and trabecular microstructure at the peripheral bone than alfacalcidol which needs further more studies.
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The use of doxorubicin (DOX) to treat various tumors is limited by its cardiotoxicity. This study aimed to investigate and compare the cardioprotective effects of nicotinamide (NAM) and alfacalcidol (1α(OH)D3), against DOX-induced cardiotoxicity. Sprague Dawley male rats received DOX (5 mg/kg, i.p.) once/week for four consecutive weeks. Treated groups received either NAM (600 mg/kg, p.o.) for 28 consecutive days or 1α(OH)D3 (0.5 ug/kg, i.p.) once/week for four consecutive weeks. DOX elicited marked cardiac tissue injury manifested by elevated serum cardiotoxicity indices, conduction and histopathological abnormalities. Both NAM and 1α(OH)D3 successfully reversed all these changes. From the mechanistic point of view, DOX provoked intense cytosolic and mitochondrial calcium (Ca2+) overload hence switching on calpain1 (CPN1) and mitochondrial-mediated apoptotic cascades as confirmed by upregulating Bax and caspase-3 while downregulating Bcl-2 expression. DOX also disrupted cardiac bioenergetics as evidenced by adenosine triphosphate (ATP) depletion and a declined ATP/ADP ratio. Moreover, DOX upregulated the Ca2+ sensor; calmodulin kinase II gamma (CaMKII-δ) which further contributed to cardiac damage. Interestingly, co-treatment with either NAM or 1α(OH)D3 reversed all DOX associated abnormalities by preserving Ca2+ homeostasis, replenishing ATP stores and obstructing apoptotic events. Additionally, DOX prompted nuclear factor kappa B (NF-κB) dependent inflammatory responses and subsequently upregulated interleukin-6 (IL-6) expression. Co-treatment with NAM or 1α(OH)D3 effectively obstructed these inflammatory signals. Remarkably, NAM showed superior beneficial cardioprotective properties over 1α(OH)D3. Both NAM and 1α(OH)D3 efficiently attenuated DOX-cardiomyopathy mainly via preserving Ca2+ homeostasis and diminishing apoptotic and inflammatory pathways. NAM definitely exhibited effective cardioprotective capabilities over 1α(OH)D3.
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Cálcio/metabolismo , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/etiologia , Doxorrubicina/efeitos adversos , Homeostase/efeitos dos fármacos , Complexo Vitamínico B/farmacologia , Vitamina D/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/metabolismo , Cardiotoxicidade/metabolismo , Regulação para Baixo/efeitos dos fármacos , Coração/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
Combination therapy of active vitamin D3 with some bisphosphonates (BPs) has been reported to be clinically beneficial. However, combination therapy of eldecalcitol (ELD) with BP has to date not been validated as to whether it is beneficial in the clinical setting. Preclinical studies suggested that simultaneous treatment with ELD and some BPs is more effective than monotherapy. However, the relative potency of various BPs, when used in combination with ELD, is completely unknown. In this study, we examined and compared the effects of risedronate (RIS), alendronate (ALN), and minodronate (MIN) alone or in combination with ELD on bone mass, microarchitecture, strength, and material properties in ovariectomized Sprague-Dawley rats aged 13 weeks. RIS, ALN, MIN, and ELD were administered five times weekly for 16 weeks. Micro-computed tomography analysis, compression test, and Fourier transform infrared (FTIR) imaging analysis were performed 16 weeks after treatment initiation. Trabecular and cortical bone mineral density (BMD) in the fourth lumbar vertebra (L4) significantly increased in the RIS + ELD, ALN + ELD, and MIN + ELD groups compared with the vehicle group. Moreover, the bone microarchitecture of L4 in all the BP + ELD groups also significantly improved. On mechanical testing of L4, the maximum load was significantly increased in the RIS + ELD and ALN + ELD groups. FTIR analysis revealed that the mineral-to-collagen ratio of trabecular bone in L3 of all the BP + ELD groups was significantly increased compared with the vehicle group. By contrast, the carbonate-to-phosphate ratio, a parameter of mineral immaturity, was significantly decreased in the RIS + ELD and ALN + ELD groups. BP + ELD improved the BMD and structural properties of the bone to a similar extent. RIS + ELD and ALN + ELD also improved bone strength. Furthermore, treatment with BP + ELD improved the bone material. These results suggest that the combination therapy of BP and ELD is beneficial and warrants further clinical trials.
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OBJECTIVE: Hypercalciuria, impaired kidney function and renal calcifications are common in chronic hypoparathyroidism (HypoPT). We aimed to study associations between indices of known importance to the kidney in HypoPT by hypothesizing adverse effects of hypercalciuria on renal outcomes. DESIGN: We used cross-sectional design. PATIENTS: We identified all patients followed for chronic HypoPT at our department and who had been examined by a 24-h urine collection for measurement of renal calcium excretion (24 h U-Ca). MEASUREMENTS: By chart review, we identified additional biochemistry measured in close connection with the collection of urine, as well as demographic, treatments and anthropometrics. RESULTS: The 166 included patients (79.5% females) had a high prevalence of hypercalciuria (65.7%). In multiple adjusted analyses, hypercalciuria was in an independent manner inversely associated with (residual) levels of plasma PTH and positively associated with levels of 1,25-dihydroxyvitamin D and ionized calcium as well as 24 h U-phosphate, gender, and etiology (surgical vs. non-surgical). Overall, this model explained 54% (p < .001) of the variation in the presence of hypercalciuria. Chronic kidney disease stage three or above was present in 18.3% of the patients, and 42.6% of the 54 patients examined by renal imaging had renal calcifications. However, neither renal function nor renal calcifications were associated with 24 h U-Ca. CONCLUSIONS: Hypercalciuria, impaired renal function and renal calcifications are common in hypoparathyroidism. Hypercalciuria is to a large extent explained by indices of known physiological importance to 24 h U-Ca. However, in the present study, a high renal calcium excretion did not explain renal impairment or kidney calcifications.
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Hipercalciúria , Hipoparatireoidismo , Cálcio , Cálcio da Dieta , Estudos Transversais , Feminino , Humanos , Hipercalciúria/complicações , Hipoparatireoidismo/complicações , Masculino , Hormônio ParatireóideoRESUMO
CONTEXT: Alfacalcidol and calcitriol are commonly used for managing hypoparathyroidism. Their relative merits have not been systematically assessed. OBJECTIVE: We compared the effect of alfacalcidol and calcitriol on phosphatemic control, hypercalciuria, and associated factors in idiopathic-hypoparathyroidism (IH). DESIGN AND SETTING: Open-label randomized controlled trial, tertiary care center. SUBJECTS AND METHODS: IH patients with optimal calcemic control on alfacalcidol were continued on the same (nâ =â 20) or switched to calcitriol (nâ =â 25) at half of the ongoing alfacalcidol dose. The dose was adjusted during follow-up to maintain serum total calcium between 8.0 and 9.5 mg/dL. Serum calcium, phosphorus, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, 24-h urine calcium-to-creatinine ratio, and fractional excretion of phosphorus (FEPh) were measured at baseline and 6 months. Plasma intact-FGF23 was measured at final follow-up. RESULT: Patients receiving alfacalcidol and calcitriol had comparable serum calcium at 6 months (8.7â ±â 0.4 vs 8.9â ±â 0.4 mg/dL, Pâ =â 0.13). Their median [interquartile range (IQR)] dose at 6 months was 2.0 (1.0-2.5) and 0.75 (0.5-1.0) µg/d, respectively. Serum 1,25(OH)2D levels were physiological in both (35.3â ±â 11.6 and 32.3â ±â 16.9 pg/mL). Serum phosphate and calcium excretion were comparable in 2 arms. A majority had hyperphosphatemia (75% vs 76%), hypercalciuria (75% vs 72%), and elevated FGF23 (116â ±â 68 and 113â ±â 57 pg/mL). Age showed significant independent association with plasma FGF23 (ßâ =â 1.9, Pâ =â 0.001). Average FEPh was low despite high FGF23. CONCLUSION: At optimal calcium control, both alfacalcidol and calcitriol lead to comparable but high serum phosphate levels, hypercalciuria, physiological circulating 1,25(OH)2D, and elevated FGF23. Further studies are required to systematically investigate other treatment options.
Assuntos
Calcitriol/uso terapêutico , Hormônios e Agentes Reguladores de Cálcio/uso terapêutico , Hidroxicolecalciferóis/uso terapêutico , Hipoparatireoidismo/tratamento farmacológico , Adulto , Cálcio/sangue , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Hipercalciúria/induzido quimicamente , Hiperfosfatemia/induzido quimicamente , Hipoparatireoidismo/sangue , Masculino , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangueRESUMO
BACKGROUND: The ability of extrarenal tissues to convert 25(OH)D (calcidiol) into 1,25(OH)2D (calcitriol) and dependence of the conversion on substrate levels provide the rationale for supplementing vitamin D in dialysis patients who usually have severe depletion of both: 25(OH)D and 1,25(OH)2D. The primary aim of the study was to compare effects of small doses of cholecalciferol (12,000 IU/week) with frequently used in Europe, small doses of alfacalcidol (1.5 µg/week) or placebo, given for 12 weeks, on serum 1,25(OH)2D in hemodialysis patients with 25(OH)D deficiency. Secondary outcomes were changes in serum calcium, phosphate, 25(OH)D, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23) and sclerostin during the treatment. METHODS: This was a prospective, randomized, partly double-blind (cholecalciferol vs. placebo) study. Out of 522 patients dialyzed in 5 centers in the Mazovian Province, 93 gave informed consent and met the inclusion criteria: any vitamin D metabolites and calcimimetics naïve; no history of liver or intestinal disease; serum 25(OH)D <20 ng/ml, iPTH <1,000 ->110 pg/ml, calcium <10.2, and phosphate <6.8 mg/dl. The subjects were stratified by serum iPTH, then randomized into 3 groups according to the treatment. RESULTS: To our knowledge, this is the first study comparing head-to-head these drugs in the hemodialysis population. There were no significant differences between the groups at baseline. 81 patients completed the study. Cholecalciferol normalized serum 25(OH)D, with a mean rise from 12.9 ± 6.7 to 31.3 ± 10.1 ng/ml (p < 0.0001). This was accompanied by a marked increase of 1,25(OH)2D from 13.8 ± 9.3 to 25.1 ± 14.2 pmol/l (p < 0.0001). A rise in serum 1,25(OH)2D was also observed in alfacalcidol treated patients, however much smaller (from 13.5 ± 10.1 to 18.5 ± 11.0 pmol/l; p = 0.02). Neither cholecalciferol nor alfacalcidol treatment resulted in significant changes in serum PTH and the remaining parameters. CONCLUSIONS: In most patients, treatment with cholecalciferol in a 12,000 IU/week dose permits safe correction of 25(OH)D deficiency and is more effective than 1.5 µg/week dose of alfacalcidol in rising serum 1,25(OH)2D. This, together with a lack of influence on circulating iPTH the usefulness of such small alfacalcidol doses in hemodialysis patients is debatable.
RESUMO
A reduced supply of micronutrient vitamin D leads to a more severe course of coronavirus infection (COVID-19). Vitamin D deficiency is combined with a decrease in innate antiviral immunity and excess of inflammation. Vitamin D supplementation stimulates the synthesis of antibacterial peptides and is important for weakening the cytokine storm, reducing excessive acute and chronic inflammation, and also for compensating for chronic comorbid pathologies. Active forms of vitamin D (alfacalcidol, etc.) are of particular importance for compensating for vitamin D deficiency in elderly patients, endocrine-immune dysfunction, sarcopenia, chronic renal failure (in which the metabolism of vitamin D in the kidneys is disturbed).
Assuntos
COVID-19 , Deficiência de Vitamina D , Humanos , Idoso , Vitamina D/metabolismo , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Inflamação/tratamento farmacológico , Vitaminas/farmacologia , Vitaminas/uso terapêutico , Micronutrientes , Sistema Imunitário/metabolismo , Antivirais , AntibacterianosRESUMO
BACKGROUND: The rationale for the prescription of vitamin D analogues in patients with chronic kidney disease (CKD) is still a matter of debate. We aimed to compare native vs. active forms of vitamin D on pre-dialysis children with CKD and evaluate effects on calcium (Ca), phosphorus (P), and parathyroid hormone (PTH). METHODS: Thirty children with pre-dialysis CKD were enrolled in a prospective cross-over study. Patients were randomly classified into two groups. Group A received native cholecalciferol while group B received alfacalcidol for 3 months. After 1 month (washout period), patients were switched to receive the opposite form for another 3 months. Serum Ca, P, alkaline phosphatase (ALP), PTH, and 25(OH)D3 were measured at study start (BL-1), end of first period (FU-1), before second period (BL-2), and after second period (FU-2). RESULTS: There was significant increase in levels of 25(OH)D3 after administration of either native or active vitamin D in the first period in both groups (p < 0.001 and < 0.001, respectively) and also in the second period for both groups (p = 0.02 and < 0.001, respectively). There was no significant difference between both groups regarding changes in serum Ca (1st period; p = 0.770 and 2nd period; p = 0.412), serum P (1st period; p = 0.835, 2nd period; p = 0.052), and serum PTH (1st period; p = 0.250, 2nd period; p = 0.539). CONCLUSION: Alfacalcidol and native vitamin D3 were equally effective in decreasing PTH levels and increasing serum 25(OH)D3 in pre-dialysis CKD patients. There was no significant difference between the two forms regarding changes in serum Ca or P. Graphical abstract.