Fracturas vertebrales múltiples postsuspensión de denosumab: revisión del tema a partir de dos casos clínicos / Discontinuation of denosumab and multiple vertebral fractures: report of two cases and review of the literature

Los tratamientos para osteoporosis se indican por tiempo variable dependiendo del tipo de droga, anabólica o anticatabólica, y de la gravedad de la enfermedad. Denosumab es un anticuerpo monoclonal totalmente humano que inhibe a RANK-L evitando de esa manera la interacción entre RANKL-RANK, con la consiguiente inhibición de la formación de los osteoclastos, su activación y sobrevida. Disminuye la resorción ósea cortical y trabecular. Su administración subcutánea de 60 mg cada 6 meses al cabo de 3 años ha demostrado reducción de la resorción ósea, incremento de la densidad mineral ósea y disminución de las fracturas vertebrales, no vertebrales y de cadera. Está indicado para el tratamiento de la osteoporosis con alto riesgo de fractura. Su mecanismo de acción es reversible. Se han descripto pérdida de la DMO y elevación de los marcadores de remodelado óseo postsuspensión. Una situación clínica grave son las fracturas vertebrales múltiples postsuspensión. Este evento es infrecuente y se lo atribuye a un rebote del remodelado óseo, postulándose se postula una predisposición especial, probablemente relacionada con microRNA. Se escriben dos mujeres con osteoporosis que presentaron este cuadro. Las fracturas ocurrieron entre 7 y 10 meses posteriores a la última dosis de denosumab. Registraron elevación de C-telopéptidos y disminución de la DMO conjuntamente con las fracturas vertebrales agudas en cascada. (AU)

The duration of osteoporosis treatments depends on the drug type, anabolic or anticatabolic, and the severity of the disease. Denosumab is a fully human monoclonal antibody that inactivates RANK-L, inhibiting the RANKL-RANK interaction . This inhibits osteoclast formation, activation, and survival. It also reduces cortical and trabecular bone resorption. Subcutaneous administration of 60 mg every 6 months for 3 years has reduced bone resorption, increased bone mineral density (BMD) and decreased vertebral, non-vertebral and hip fractures. It is indicated for the treatment of osteoporosis with high risk of fracture. Denosumab mechanism of action is reversible. After discontinuation, loss of BMD and elevation of bone turnover markers have been observed. In addition, multiple vertebral fractures after the suspension of the drug have been reported. These rebound-associated vertebral fractures are rare. A special genetic predisposition related to miRNA has been proposed. Two women with this clinical presentation are described. Fractures occurred between 7 and 10 months respectively after the last dose of denosumab. They presented with an increase in circulating C-telopeptid levels and a decrease inBMD with acute multiple vertebral fractures. (AU)

Estudio comparativo de la absorción neta de calcio de dos formulaciones distintas de carbonato de calcio en mujeres posmenopáusicas / Comparative study of net calcium absorption of two different pharma¬ceutical formulations of calcium carbonate in posmenopausal women

La suplementación con calcio reduciría, sola o asociada a otra medicación para osteoporosis, la pérdida de masa ósea y el riesgo de fracturas. Sin embargo, su tasa de adherencia es baja debido a la poca tolerancia. Objetivo: comparar la tasa de absorción neta de calcio entre dos formulaciones distintas de carbonato de calcio (500 mg): comprimidos vs. mousse. Material y métodos: 11 pruebas fueron realizadas en mujeres posmenopáusicas de 58,9±3 años. El diseño fue exploratorio abierto, aleatorizado, prospectivo cruzado de fase 4. Intervención: las participantes fueron aleatorizadas en dos grupos para recibir las dos formulaciones previa suplementación con vitamina D3. La tasa de absorción neta de calcio fue estudiada por la prueba de inhibición de hormona paratiroidea (PTH). Se obtuvieron muestras de sangre: basal y en la 1a, 2a y 3a hora posadministración del calcio asignado, y de orina de 2 horas basal y al final de la prueba. Determinaciones bioquímicas: calcio, fósforo, albúmina, 25-hidroxivitamina D y hormona paratiroidea intacta y calciuria. Análisis estadístico: método de los trapecios para calcular el área bajo la curva (AUC) de la concentración de calcio en el tiempo (R Development Core Team (2008). http://www.Rp-project.org) y Anova con dos términos de error para evaluar el efecto secuencia, período y formulación. Resultados: la mayor inhibición de PTH se observó a dos horas de la toma de ambas formulaciones (comprimidos -39,2% vs. mousse -38,0%; p=ns), con similar AUC0-3 h (comprimidos 3,35; IC 95%: 3,32; 3,37 vs. mousse 3,36; IC 95%: 3,33; 3,38). Cuando analizamos tolerancia y preferencias no se observaron diferencias estadísticamente significativas entre ambas formulaciones. Conclusión: el carbonato de calcio en mousse mostró similar tasa de absorción intestinal, preferencia y tolerancia gastrointestinal que en comprimido. (AU)

Calcium supplementation, administered alone or in combination with a specific medication for osteoporosis, would reduce bone mass loss and fracture risk in postmenopausal women. However, the adherence rate to calcium supplements is low, mainly due to low tolerance. Objective: comparisson of net calcium absorption rate between two different pharmaceutical formulations of calcium carbonate (PFCa) in postmenopausal women. Materials and Methods: 11 tests were performed in postmenopausal women aged 58.9±3 yrs. Design: Comparative, randomized, prospective, open-label exploratory crossover study of calcium mousse versus calcium pills. Intervention: Participants were randomized in 2 groups to receive the 2 different PFCa (500mg): pills vs. mousse, with previous vitamin D3 supplementation. The parathyroid hormone (PTH) inhibition test and the area-under-thecurve (AUC) of calcium were analyzed. Blood samples were taken at baseline and 1, 2 and 3 hrs after intake of the assigned PFCa. Urine samples (2hs) were obtained at -baseline, after 2hs of PFCa intake and at the end of the test. Biochemical Determinations: Serum: calcium, phosphorus, albumin, 25-hydroxyvitamin D, and intact PTH. In urine: calcium. Statistical Analysis: The trapezoid rule was applied to assess AUC in time (R Development Core Team (2008). http://www.Rp-project.org). An ANOVA model with 2 error terms was used to assess the effect of sequence, period, and formulation. Results: The highest inhibition PTH rates were observed after 2 hrs of PFCa (pills -39.2% vs. mousse -38.0%; p=ns). The AUC0-3hrs for both PFCa was similar (pills 3.35; 95%CI: 3.32; 3.37 vs. mousse 3.36; 95%CI: 3.33; 3.38). No statistically significant differences were observed when we analyze tolerance and predilection. Conclusion: The calcium carbonate in mousse showed an adequate rate of intestinal absorption, similarly predilection and gastrointestinal tolerance than the pill presentation. (AU)

Are patients with lichen planus really prone to urolithiasis? Lichen planus and urolithiasis

ABSTRACT Purpose to investigate whether patients with lichen planus (LP) are really prone to urolithiasis or not. Patients and Methods We performed a prospective analysis of 40 patients diagnosed with lichen planus (LP) (group I), and 40 volunteers did not have LP before (group II). Participants were all checked for urolithiasis by radiological investigations. Blood samples were analyzed for biochemistry parameters including calcium and uric acid. 24-h urine samples were analyzed to investigate oxalate, citrate calcium, uric acid, magnesium, sodium and creatinine. Results Men/women ratio and mean age were similar between group I and II (p>0.05). A presence or history of urolithiasis was detected in 8 (20%) and 2 (%5) patients in group I and II, respectively (p<0.05). Hypocitraturia was the most common anomaly with 35% (n:14) in group I. The rate of hypocitraturia in group II was 12.5% (n:5) and the difference was statistically significantly different (p=0.036). In group I, hyperuricosuria and hyperoxaluria followed with rates of 27.5% (n:11) and 25% (n:10), respectively. The rate of hyperuricosuria and hyperoxaluria were both 5% (n:2) in group II and the differences were significant (p<0.05). Hyperuricemia was another important finding in the patients with LP. It was detected in 13 (32.5%) patients in group I and in 1 (2.5%) participant in group II (p=0.001). Conclusion According to our results, metabolic disorders of urolithiasis were highly detected in the patients with LP. However, similar to the etiology of LP, the exact reasons for these metabolic abnormalities in LP remain a mystery.

Milk-alkali syndrome secondary to the intake of calcium supplements / 영남의대학술지

Milk-alkali syndrome (MAS), a triad of hypercalcemia, metabolic alkalosis, and renal failure, is associated with ingestion of large amounts of calcium and absorbable alkali. MAS is the third most common cause of hypercalcemia in hospital, after primary hyperparathyroidism and malignant neoplasm. MAS is not often reported in the Korean literature. We describe MAS secondary to intake of calcium citrate for the treatment of osteoporosis with thoracic spine compression fracture. A 70-year-old man presented to our hospital with a 1-week history of general weakness and lethargy. He was found with acute kidney injury (serum creatinine, 4.6 mg/dL), hypercalcemia (total calcium, 14.8 mg/dL), and alkalosis. Laboratory evaluation excluded both hyperparathyroidism and malignancy. Mental status and serum calcium level was normalized within a week after proper hydration and intravenous administration of furosemide. However, he developed aspiration pneumonia, pseudomembranous colitis, and sepsis with multi-organ failure. Despite intensive treatment including inotropics, mechanical ventilation, and renal replacement therapy, he expired with no signs of renal recovery on the 28th hospital day.

SECONDARY HYPERPARATHYROIDISM AFTER BARIATRIC SURGERY: TREATMENT IS WITH CALCIUM CARBONATE OR CALCIUM CITRATE? / HIPERPARATIREOIDISMO SECUNDÁRIO APÓS CIRURGIA BARIÁTRICA: TRATAR COM CARBONATO OU CITRATO DE CÁLCIO?

Background:Bariatric surgery, especially Roux-en-Y gastric bypass, can cause serious nutritional complications arising from poor absorption of essential nutrients. Secondary hyperparathyroidism is one such complications that leads to increased parathyroid hormone levels due to a decrease in calcium and vitamin D, which may compromise bone health.Aim: To compare calcium carbonate and calcium citrate in the treatment of secondary hyperparathyroidism.Method: Patients were selected on the basis of their abnormal biochemical test and treatment was randomly done with citrate or calcium carbonate.Results: After 60 days of supplementation, biochemical tests were repeated, showing improvement in both groups.Conclusion: Supplementation with calcium (citrate or carbonate) and vitamin D is recommended after surgery for prevention of secondary hyperparathyroidism.

Racional:A cirurgia bariátrica, especialmente a gastroplastia em Y-de-Roux, pode causar complicações nutricionais importantes que derivam da má absorção de nutrientes essenciais. O hiperparatireoidismo secundário é uma delas que cursa com o aumento do hormônio da paratireoide e consequente diminuição de cálcio e vitamina D, o que pode comprometer a saúde óssea.Objetivo: Comparar o tratamento do hiperparatireoidismo secundário com o uso de carbonato e citrato de cálcio.Métodos: Os pacientes foram selecionados a partir de seus exames bioquímicos alterados e o tratamento foi sugerido aleatoriamente com citrato ou carbonato de cálcio.Resultados: Após 60 dias de suplementação foram reavaliados os exames bioquímicos e percebeu-se melhora em ambos os grupos, tanto com citrato como com carbonato de cálcio.Conclusão: Recomenda-se o uso de suplementação de cálcio (citrato ou carbonato) e vitamina D após a operação para prevenção do hiperparatireoidismo secundário.

In Vitro Enamel Remineralization by Low-Fluoride Toothpaste with Calcium Citrate and Sodium Trimetaphosphate

The objective of this study was to evaluate in vitro the effect of a low fluoride toothpaste (450 µgF/g, NaF) combined with calcium citrate (Cacit) and sodium trimetaphosphate (TMP) on enamel remineralization. Bovine enamel blocks had the enamel surface polished sequentially to determine the surface hardness. After production of artificial carious lesions, the blocks selected by their surface hardness were submitted to remineralization pH cycling and daily treatment with dentifrice suspensions (diluted in deionized water or artificial saliva): placebo, 275, 450, 550 and 1,100 µgF/g and commercial dentifrice (positive control, 1,100 µgF/g). Finally, the surface and cross-section hardness was determined for calculating the change of surface hardness (%SH) and mineral content (%∆Z). Fluoride in enamel was also determined. The data from %SH, %∆Z and fluoride were subjected to two-way analysis of variance followed by Student-Newman-Keuls's test (p<0.05). The mineral gain (%SH and %∆Z) was higher for toothpastes diluted in saliva (p<0.05), except for the 450 µgF/g dentifrice with Cacit/TMP (p>0.05). The 450 Cacit/TMP toothpaste and the positive control showed similar results (p>0.05) when diluted in water. A dose-response was observed between fluoride concentration in toothpastes and fluoride present in enamel, regardless of dilution. It was concluded that it is possible to enhance the remineralization capacity of low F concentration toothpaste by of organic (Cacit) and inorganic (TMP) compounds with affinity to hydroxyapatite.

O objetivo do presente trabalho foi avaliar in vitro o efeito de um dentifrício com reduzida concentração de fluoreto (450 µgF/g, NaF) associado ao citrato de cálcio (Cacit) e trimetafosfato de sódio (TMP) na remineralização do esmalte. Blocos de esmalte bovino tiveram sua superfície de esmalte polida seqüencialmente para determinação da dureza de superfície. Após o desenvolvimento de lesões artificiais de cárie, os blocos selecionados através da dureza de superfície foram submetidos a ciclagem de remineralização e tratamento diário com suspensões de dentifrícios (diluição em água deionizada ou saliva artificial): placebo, 275, 450, 550 e 1.100 µgF/g e com dentifrício comercial (controle positivo, 1.100 µgF/g). Ao término, determinou-se a dureza de superfície e em secção longitudinal, para cálculo da variação da dureza de superfície (%SH) e do conteúdo mineral (%∆Z). O fluoreto presente no esmalte também foi determinado. Os dados de %SH, %∆Z e fluoreto foram submetidos a análise de variância a dois critérios seguido pelo teste de Student-Newman-Keuls (p<0,05). O ganho mineral (%SH e %∆Z) foi maior para os dentifrícios diluídos em saliva (p<0,05), exceto para os dentifrícios 450 µg F/g com Cacit/TMP (p>0,05). Os dentifrícios 450 Cacit/TMP e controle positivo apresentaram resultados semelhantes (p>0,05) quando diluídos em água. Uma relação dose-resposta foi observada entre a concentração de fluoreto nos dentifrícios e o fluoreto presente no esmalte, independente da diluição. Concluiu-se que é possível melhorar a capacidade de remineralização de dentifrícios com reduzida concentração de fluoreto pela adição de compostos orgânico (Cacit) e inorgânico (TMP) com afinidade a hidroxiapatita.

Calcium citrate improves the epithelial-to-mesenchymal transition induced by acidosis in proximal tubular cells / Citrato de cálcio melhora a transição epitélio-mesenquimal induzida por acidose em células do túbulo proximal

INTRODUCTION: Epithelial-to-mesenchymal transition (EMT) is a key event in renal fibrosis. The aims of the study were to evaluate acidosis induced EMT, transforming-growth-factor (TGF) β1 role and citrate effect on it. METHODS: HK2 cells (ATCC 2290) were cultured in DMEM/HAM F12 medium, pH 7.4. At 80% confluence, after 24 hr under serum free conditions, cells were distributed in three groups (24 hours): A) Control: pH 7.4, B) Acidosis: pH 7.0 and C) Calcium citrate (0.2 mmol/L) + pH 7.0. Change (Δ) of intracellular calcium concentration, basal and after Angiotensin II (10-6M) exposition, were measured to evaluate cellular performance. EMT was evaluated by the expression of α-smooth muscle actin (α-SMA) and E-cadherin by immunocytochemistry and/or Western blot. TGF-β1 secretion was determined by ELISA in cell supernatant. RESULTS: At pH 7.0 HK2 cells significantly reduced E-cadherin and increased α-SMA expression (EMT). Supernatant TGF-β1 levels were higher than in control group. Calcium citrate decreased acidosis induced EMT and improved cells performance, without reduction of TGF-β production. CONCLUSIONS: Acidosis induces EMT and secretion of TGF-β1 in tubular proximal cells in culture and citrate improves cellular performance and ameliorates acidosis induced EMT.

INTRODUÇÃO: A transição epitélio-mesenquimal (TEM) é um evento chave na fibrose renal. Os objetivos do estudo foram avaliar se o citrato seria capaz de reverter a TEM induzida por acidose, e qual seria o papel do fator de crescimento transformador (TGF) β1 neste evento. MÉTODOS: Células de túbulo proximal (HK2) foram cultivadas em meio DMEM-F12, pH 7,4. Após confluência, as células foram distribuídas em três grupos A) controle: pH 7,4, B) Acidose: pH 7,0 e C) Acidose: pH 7,0 + citrato de cálcio (0,2 mmol/L). A variação na concentração de cálcio intracelular, antes e após a adição de angiotensina II (10-6M) foi medida para avaliar o desempenho celular. TEM foi avaliada pela expressão de α-actina de músculo liso (α-SMA) e E-caderina por imunocitoquímica e/ou de Western blot. A secreção de TGF-β1 foi determinada por ELISA no sobrenadante. RESULTADOS: Em pH 7,0, houve redução significante na expressão de E-caderina e aumento de α-SMA indicando a presença de TEM e a concentração de TGF-β1 foi maior do que no grupo controle. O citrato de cálcio melhorou TEM induzida pela acidose e a resposta das células à angiotensina II, sem redução do TGF-β. CONCLUSÕES: Acidose induz TEM e secreção de TGF-β1 em células tubulares proximais em cultura e o citrato melhora o desempenho celular e a TEM induzida por acidose.

Anticaries effect of dentifrices with calcium citrate and sodium trimetaphosphate

Because of the growing concerns regarding fluoride ingestion by young children and dental fluorosis, it is necessary to develop new dentifrices. OBJECTIVE: The aim of this study was to evaluate the effect of dentifrices with calcium citrate (Cacit) and sodium trimetaphosphate (TMP) on enamel demineralization. MATERIAL AND METHODS: Enamel blocks (n=70), previously selected through surface hardness analysis, were submitted to daily treatment with dentifrices diluted in artificial saliva and to a pH-cycling model. The fluoride concentration in dentifrices was 0, 250, 450, 550, 1,000 and 1,100 µg F/g. CrestTM was used as a positive control (1,100 mg F/g). Cacit (0.25 percent) and TMP (0.25 percent) were added to dentifrices with 450 and 1,000 µg F/g. Surface hardness was measured again and integrated loss of subsurface hardness and fluoride concentration in enamel were calculated. Parametric and correlation tests were used to determine difference (p<0.05) and dose-response relationship between treatments. RESULTS: The addition of Cacit and TMP did not provide a higher fluoride concentration in enamel, however it reduced (p<0.05) mineral loss when compared to other dentifrices; the dentifrice with Cacit and TMP and a low fluoride concentration presented similar results when compared to a dentifrice with 1,100 mg F/g (p>0.05). CONCLUSIONS: Dentifrices with 450 and 1,000 µg F/g, Cacit and TMP were as effective as a gold standard one.

Effect of calcium citrate on bone integration in a rabbit femur defect model

OBJECTIVE@#To explore effect of calcium citrate on bone integration in a rabbit femur defect model, and to compare the bone formation with different sizes by radiological and histological study.@*METHODS@#Twenty-four male Japanese white rabbits were randomly divided into three groups (Group A, B, C) in this study. Under anesthesia, defects of four sizes (1.2, 1.5, 2.0 and 2.5 mm) were created in each of the rabbits. Commercially pure calcium citrate powder was placed inside the medullary compartment of the femur (Experimental), while in the contralateral femur (Control) nothing was implanted. The defects were analyzed using radiography and histological analysis by using Imagepro-Plus 6.0 software after animal was sacrificed at 4th(Group A), 6th(Group B) and 8th(Group C) weeks postoperatively. Four samples were analyzed for each size of defect and each healing period.@*RESULTS@#The histological and the radiologic evaluation were performed after sacrification of all rabbits on postoperative 4th and 6th weeks, It showed significant difference between the experimental group and the control group when these defects were less than or equal to 2.0 mm. No statistical difference was observed when these defects were larger than 2.0 mm at all healing periods except at the 4th week.@*CONCLUSIONS@#Calcium citrate affects the early periods of bone defects healing mechanism in Japanese white rabbits positively, especially when the defect is not too large. We suggest further studies on calcium citrate to determine the effects of various dosages, administration ways and the experimental time on the bone defects.

Calcium citrate: a new biomaterial that can enhance bone formation in situ / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the effect of a new biomaterial combining calcium citrate and recombinant human bone morphogenetic protein-2 (rhBMP-2) on bone regeneration in a bone defect rabbit model.</p><p><b>METHODS</b>Totally 30 male New Zealand white rabbits were randomly and equally divided into calcium citrate-rhBMP-2 (CC-rhBMP-2) group and rhBMP-2 only group. Two 10 mm-long and 5 mm-deep bone defects were respectively created in the left and right femoral condyles of the rabbits. Subsequently 5 pellets of calcium citrate (10 mg) combined with rhBMP-2 (2 mg) or rhBMP-2 alone were implanted into the bone defects and compressed with cotton swab. Bone granules were obtained at 2, 4 and 6 weeks after procedure and received histological analysis. LSD t-test and a subsequent t-test were adopted for statistical analysis.</p><p><b>RESULTS</b>Histomorphometric analysis revealed newly formed bones, and calcium citrate has been absorbed in the treatment group. The percent of newly formed bone area in femoral condyle in control group and CC-rhBMP-2 group was respectively 31.73%+/-1.26% vs 48.21%+/-2.37% at 2 weeks; 43.40%+/-1.65% vs 57.32%+/-1.47% at 4 weeks, and 51.32%+/-7.80% vs 66.74%+/-4.05% at 6 weeks (P less than 0.05 for all). At 2 weeks, mature cancellous bone was observed to be already formed in the treatment group.</p><p><b>CONCLUSION</b>From this study, it can be concluded that calcium citrate combined with rhBMP-2 signifcantly enhances bone regeneration in bone defects. This synthetic gelatin matrix stimulates formation of new bone and bone marrow in the defect areas by releasing calcium ions.</p>

Tiempo de filtración del citrato de calcio y magnesio obtenido a partir de dolomita cubana / Filtration time for calcium cytrate and magnesium from the Cuban dolomite

El citrato de calcio y magnesio es una materia prima de calidad farmacéutica obtenida a partir de dolomitas cubanas, con la finalidad de ser empleada en la producción de formas terminadas para suplir calcio y magnesio en personas con deficiencias de estos minerales. Como parte de la optimización del proceso tecnológico de obtención, se estudió el tiempo de filtración con el objetivo de evaluar el comportamiento a escalas superiores. Para ello se realizó un estudio de desescalado para determinar las condiciones en la escala de banco, empleando como criterio de escalado mantener igual consumo de potencia por unidad de volumen. A través de la ecuación fundamental de la filtración, se determinó el tiempo de esta operación. El estudio de filtración dio como resultados que el valor de la resistencia del medio filtrante era Rm= 6,08 × 1010 m-1 y la resistencia de la torta a= 1,239 × 1010 m/kg-1 a una diferencia de presión constante (Dp= 9,99 × 104 kg/m·s2). Mientras que el tiempo medio de filtración fue de 494,6 s (8,24 ± 3,0 min). En conclusión, los resultados mostraron que el tiempo de filtración es adecuado para el proceso tecnológico estudiado, y el estudio de escalado demostró la viabilidad del proceso de filtración

Calcium and magnesium citrate is a raw material of pharmaceutical quality obtained from Cuban dolomites to be used in those people with deficiency in these two minerals. As part of the technological process optimization, the filtering time was studied to evaluate the possible behaviour at higher scales. To this end, one scale-down study was made to determine the conditions at bench scale by keeping the same power consumption per volume unit. The fundamental filtering equation allowed determining the time for this operation. The results of this study showed that the resistance value of the filtering material was Rm= 6.08 · 1010 m-1 and the resistance of the mass was a= 1,239 , 1010 m·kg-1 at constant pressure (Dp= 9,99 × 104 kg/m·s2). The filtration time was 494,6 s (8,24 ± 3,0 min). The results showed that the filtration time was correct for the studied technological process and the scale up study demonstrated the feasibility of the filtration process

Eficiencia del proceso de lavado en la obtención del citrato de calcio y magnesio a escala de banco / Effectiveness of washout process to obtain calcium and magnesium citrate at bench scale

Como parte de la optimización del proceso tecnológico para obtener citrato de calcio y magnesio a partir de dolomitas, se estudió a escala de banco la etapa de lavado para disminuir el contenido de àcido cítrico libre. Las variantes de lavado estudiadas permitieron disminuir el contenido de àcido cítrico libre por debajo del 3 por ciento, mientras que los valores de calcio y magnesio son similares a los del lote antes de realizar el proceso de lavado. Por otro lado, el estudio toxicológico en ratas, comprobó que los lotes a los cuales se les aplicó las diferentes variantes de lavado no provocaron irritabilidad gástrica a las dosis de 2 000 mg/kg de peso corporal, por lo que se puede afirmar que el proceso de lavado establecido es adecuado para garantizar la calidad de la materia prima.

As part of the technological process optomization to obtain calcium citrate and magnesium from dolomites, we studied at bench scale, the washout stage to decrease the free citric acid content. Washout variants allowed to decrease the free citric acid content under 3 percent, whereas the calcium and magnesium values are similar to those of batch before to carry out the wahout process. On the other hand, toxicity study in rats, proved that the batches where different washout variables were applied not provoke gastric irritability at doses of 2 000 mg/kg of body weight confirming that above mentioned established process is approproate to guarantee the raw material quality.

Secado del citrato de calcio y magnesio a escala de banco / Calcium magnesium citrate drying at bench scale

El citrato de calcio y magnesio es una materia prima obtenida a partir de dolomítas. Como parte de la optimización del proceso tecnológico, se estudió a escala de banco la etapa de secado para predecir su comportamiento a escalas superiores. Los resultados de este estudio mostraron que a partir de las 7:30 h de secado la muestra alcanza un contenido de humedad por debajo del 5 por ciento. Por otro lado, se observó que en las primeras 6 h la cantidad de agua evaporada representa más del 85 por ciento de la cantidad total presente en la muestra. Se concluye que el proceso de secado es adecuado para garantizar que el citrato de calcio y magnesio tenga un contenido de humedad por debajo de lo exigido para materias primas de calidad farmacéutica.

Calcium and magnesium citrate is a raw material obtained from dolomite. As part of the optimization of technological process, we studied it at bench scale, the dry stage to predict its behavior at higher scales. Results of this study showed that from 7:30 hours, sample drying reaches a humidity content lower 5 percent. Besides, we noted that during the first 6 hours, quantity of evaporation water represents more than 85 percent of total quantity present in sample. We conclude that drying process is appropriate to guarantees that calcium and magnesium citrate has humidity content lower than that required for raw products of pharmaceutical quality.

The Effect of Vitamin K2 in Addition to Risedronate on the Patients with Postmenopausal Osteoporosis

OBJECTIVE: To assess the effect of vitamin K2 in addition to risedronate on postmenopausal osteoporosis METHOD: We enrolled 21 postmenopausal osteoporosis women (age: 65.2+/-7.8 years). Ten subjects received risedronate (35 mg, weekly) and vitamin K2 (45 mg, daily) and eleven subjects only received risedronate. They all received calcium citrate 2,130 mg and vitamin D 600 IU daily. The duration of treatment was 7.7+/-1.4 months. Bone mineral density (BMD) of lumbar spine and both femurs, serum osteocalcin and urine deoxypyridinoline were examined at baseline and after treatment. RESULTS: After treatment, BMD, serum osteocalcin and urine deoxypyridinoline were improved in each group but there was no statistical difference between the groups. CONCLUSION: There was no evidence of the benefit of vitamin K2 in addition to risedronate in bone metabolism on postmenopausal osteoporosis.

Efecto del calcio dietético vs el citrato de calcio sobre marcadores bioquímicos convencionales en mujeres perimenopáusicas / Effect of dietary calcium vs. calcium citrate on conventional biochemical markers in perimenopausal women

OBJETIVO: Comparación del efecto del citrato de calcio y una dieta con calcio en los alimentos sobre marcadores bioquímicos convencionales. MATERIAL Y MÉTODOS: Se estudiaron 82 mujeres de 30 a 35 años de edad divididas al azar en tres grupos: grupo control: 23 mujeres sin modificación de sus hábitos alimenticios ni actividad física. Grupo con calcio dietético: 28 mujeres con un régimen de 1 000 mg de calcio más actividad física de 30 minutos tres veces por semana. Grupo con citrato de calcio: 31 mujeres suplementadas con citrato de calcio (600 mg), más 500 mg de calcio dietético, y actividad física de 30 minutos tres veces por semana durante siete meses. Se hizo densitometría ósea de calcáneo para clasificarlas en normal y osteopenia, se determinaron parámetros bioquímicos al inicio y final del estudio: fosfatasa alcalina, magnesio, calcio y fósforo séricos, y relación calcio/creatinina en orina. RESULTADOS: El 34 por ciento de las mujeres presentaron osteopenia; éstas tuvieron una reducción significativa en el calcio final en el grupo de citrato de calcio en comparación con el grupo de calcio dietético (p<0.05, 7.4 mg/dl vs 8.8 mg/dl). En la valoración final se observó hipermagnesemia significativa en el grupo de calcio dietético, en comparación con el grupo de citrato de calcio (p<0.05). El fósforo disminuyó en el grupo con calcio dietético (3.5 a 3.2 mg/dl) (p>0.05). La relación calcio/creatinina fue normal en todos los grupos. CONCLUSIONES: El grupo con calcio dietético presentó mayor formación ósea que el grupo con citrato de calcio; en ninguno de ellos se observó resorción ósea.

Urolithiasis in patients on chronic hemodialysis

Reports were conflicting with respects to the composition of calculi formed in patients who were kept on hemodialysis and also on the pathogenetic factors involved in their formation. This study was, therefore, conducted to investigate these debates. Patients and methods: renal calculi form 38 hemodialysis patients were subjected to morphological study with microscopic examination and constitutional analysis with infrared spectrophotometry. patients' calculi were mainly consisting of oxalo-protein calculi with > 30% calcium oxalate as a total stone content [18 patients, or 47%]. They could be a consequence to metabolic factors, such as high urinary oxalate and low urinary citrate concentration, and to iatrogenic factors, namely vitamin D3 and calcium salts supplementation. In 14 [37%] patients, calculi were made of sole proteins or in association with < 30% calcium oxalate, and were observed mainly in patients with primary glomerular disease. Aluminum-magnesium urate calculi, which may be related to aluminum overload were seen in the remaining 6 [16%] patients. metabolic and iatrogenic conditions come as the predominant factors incriminated in pathogenesis of most calculi formed by hemodialysis patients. The precise analysis of such calculi is therefore, higher recommended as it can offer useful information on pathogenesis, and hence a possible approach to their prophylaxis

Contribuiçäo do laboratório de análises clínicas no diagnóstico metabólico da litíase renal / The importance of laboratory tests in the metabolic evaluation of nephrolithiasis

Cerca de 5 porcento da populaçäo brasileira é portadora de litíase renal, o que corresponde a cerca de 7 milhöes de litiásicos brasileiros. É uma patologia que acomete indivíduos jovens, geralmente na terceira década de vida, nos seus anos mais produtivos, além de sua recorrência ser muito elevada. Apesar do avanço no tratamento da litíase renal nos últimos anos, através de técnicas näo invasivas, estes métodos só servem para retirar o cálculo, ou seja, eliminam a consequência da doença e näo a sua causa. Desta forma, todo paciente com urolitíase ou que já apresentou cálculo e, principalmente, aquele com história de múltiplos cálculos devem submeter-se a realizaçäo de um estudo metabólico. Com este objetivo, 73 indivíduos com litíase renal recorrente foram estudados. Destes, apenas 1 (1,4 porcento) näo apresentou alteraçäo em nenhum dos parâmetros analisados. Os principais distúrbios metabólicos encontrados foram hipercalciúria, hipernatriúria, hipocitratúria, hipomagnesúria e hiperuricosúria. Este tipo de estudo é importante e o laboratório de análises clínicas contribui na elucidaçäo dos mecanismos fisiopatogênicos responsáveis pela formaçäo de cálculos e na indicaçäo de uma terapêutica mais racional, adequada e eficaz

Influência de diferentes citratos na prevençäo da cárie dentária em ratos (Rattus norvegicus, var-albinus) / Influence of different citrates on the prevention of dental caries in rats (Rattus novergicus, var-albinus)

Este trabalho teve como objetivo verificar o efeito de diferentes citratos na incidência de cárie em ratos (Rattus norvegicus, var-albinus). Para tal, foram utilizados 96 ratos (48 machos e 48 fêmeas) com 21 dias de idade e distribuídos aleatoriamente em 6 grupos com 16 animais cada: G.I - dieta cariogênica (controle); G.II - dieta cariogênica + citrato de cálcio 1 por cento; G.III - dieta cariogênica + citrato de magnésio 0,9 por cento; G.IV - dieta cariogênica + citrato de potássio 0,65 por cento; G.V - dieta cariogênica + citrato de amônio bibásico, 0,45 por cento; G.VI - dieta cariogênica + ácido cítrico 0,38 por cento. A dieta cariogênica utilizada foi a 2000 a, proposta por REGOLATI; MUHLHEMANN 45. Os animais de todos os grupos, foram pesados inicialmente aos 21 dias de idade e depois semanalmente até atingirem 64 dias de idade após o que, foram sacrificados. Os segmentos ósseos maxilares e mandibulares foram removidos hemisseccionados e preparados para o exame das lesöes de cárie de sulco de molares segundo o método de KEYES 21. Os dados obtidos foram anotados em fichas apropriadas para posteriormente serem analisados estatisticamente, através de um teste näo paramétrico a um modelo de análise de variância a um critério de Kruskal-Wallis, permitindo desta maneira concluir que: - O íon citrato apresenta efeito anticariogênico. - O ácido cítrico, demonstrou um maior efeito na reduçäo da cárie dentária quando comparado aos sais de citrato, com diferenças estatisticamente significantes. - Os sais de citrato reduziram a incidência de cárie, a nível de significância estatística, porém, quando comparados entre si, näo demonstraram diferenças estatisticamente significantes. - Os diferentes tratamentos recebidos pelos ratos durante todo o período experimental näo alteraram o ganho de peso desses animais