A comparison between the combined effect of calcium carbonate with sucroferric oxyhydroxide and other phosphate binders: an in vitro and in vivo experimental study.

BACKGROUND: Approximately 30% of patients on dialysis received combination therapy for their phosphate binder prescription; however, few studies for combined effects of phosphate binders are reported. For the purpose of evaluating the efficacy of combination therapy, we compared the efficacy of sucroferric oxyhydroxide (PA21) combined with calcium carbonate with that of lanthanum carbonate hydrate, sevelamer hydrochloride, and ferric citrate hydrate combined with calcium carbonate. METHODS: For in vitro studies, calcium carbonate and the other phosphate binders alone or in combination were stirred in phosphate solution at pH 2-8 for 2 h. After centrifuging the suspension, the phosphorus level in the supernatant was determined. For in vivo studies, rats were orally administered calcium carbonate and the other phosphate binders (except for sevelamer hydrochloride) alone or in combination, followed by oral administration of phosphate solution adjusted to pH 2 or 7. Serum samples were collected from the rats at predetermined timepoints and the serum phosphorus levels were determined and analyzed using a two-way analysis of variance. RESULTS: In the in vitro study, the measured phosphate-binding capacity of combining sevelamer hydrochloride, PA21, and lanthanum carbonate hydrate with calcium carbonate was approximately equal to or greater than the theoretical values under most conditions. Furthermore, these combined effects were insensitive to pH in that order. The measured phosphate-binding capacity of ferric citrate hydrate combined with calcium carbonate was smaller than the theoretical values, and the combination did not exhibit efficacy under any of the tested conditions. In the in vivo study, the combined effect of PA21 and calcium carbonate at both pH values and that of lanthanum carbonate hydrate and calcium carbonate at pH 2 were additive. In contrast, the combined effect of lanthanum carbonate hydrate and calcium carbonate at pH 7 and that of ferric citrate hydrate and calcium carbonate at pH 2 were antagonistic. CONCLUSIONS: These results suggest that coadministration of PA21 and calcium carbonate showed good and relatively stable efficacy throughout the range of the gastrointestinal pH and that combining lanthanum carbonate hydrate and ferric citrate hydrate with calcium carbonate may not produce the expected efficacy under certain conditions.

Effects of chia (Salvia hispanica L.) on calcium bioavailability and inflammation in Wistar rats.

Chia is a good source of calcium, however it is not been previously reported its bioavailability associated with an inflammatory condition. Thus, the present study evaluated the effect of chia on calcium bioavailability, inflammation, and oxidative stress in Wistar rats fed a high-fat diet or standard diet for 35 days. Chia consumption resulted in lower calcium balance and calcium absorption and retention rates. In addition, the urinary calcium concentration was lower in groups that were fed chia. The bone resistance of animals feed chia was lower than that in rats fed the standard diet receiving calcium carbonate. Animals that were fed chia showed lower total, very low-density lipoprotein, and low-density lipoprotein cholesterol levels than animalsfed calcium carbonate. Animals fed standard diet showed higher superoxide dismutase plasma concentrations than animals in the high fat calcium carbonate group. PPAR-α protein levels were higher in animals fed chia whereas TNF-α and IL-10 were lower in these animals. NFκB mRNA expression and protein levels were lower in the groups that received chia compared with HFD + CC. Chia intake presented low calcium bioavailability regardless of the type of diet consumed and was able to improved inflammation and the lipid profile in young Wistar rat. Besides this, the consumption of this seed increased the activity of antioxidants enzymes.

Hypoparathyroidism: what is the best calcium carbonate supplementation intake form? / Hipoparatireoidismo: qual é a melhor forma de ingestão de suplemento de carbonato de cálcio?

Abstract Introduction: In hypoparathyroidism, calcium supplementation using calcium carbonate is necessary for the hypocalcemia control. The best calcium carbonate intake form is unknown, be it associated with feeding, juice or in fasting. Objective: The objective was to evaluate the calcium, phosphorus and calcium × phosphorus product serum levels of hypoparathyroidism women after total thyroidectomy, following calcium carbonate intake in three different forms. Methods: A crossover study was carried out with patients presenting definitive hypoparathyroidism, assessed in different situations (fasting, with water, orange juice, breakfast with a one-week washout). Through the review of clinical data records of tertiary hospital patients from 1994 to 2010, 12 adult women (18-50 years old) were identified and diagnosed with definitive post-thyroidectomy hypoparathyroidism. The laboratory results of calcium and phosphorus serum levels dosed before and every 30 min were assessed, for 5 h, after calcium carbonate intake (elementary calcium 500 mg). Results: The maximum peak average values for calcium, phosphorus and calcium × phosphorus product were 8.63 mg/dL (water), 8.77 mg/dL (orange juice) and 8.95 mg/dL (breakfast); 4.04 mg/dL (water), 4.03 mg/dL (orange juice) and 4.12 mg/dL (breakfast); 34.3 mg2/dL2 (water), 35.8 mg2/dL2 (orange juice) and 34.5 mg2/dL2 (breakfast), respectively, and the area under the curve 2433 mg/dL min (water), 2577 mg/dL min (orange juice) and 2506 mg/dL min (breakfast), 1203 mg/dL min (water), 1052 mg/dL min (orange juice) and 1128 mg/dL min (breakfast), respectively. There was no significant difference among the three different tests (p > 0.05). Conclusion: The calcium, phosphorus and calcium × phosphorus product serum levels evolved in a similar fashion in the three calcium carbonate intake forms.

Resumo Introdução: No hipoparatireoidismo, a suplementação de cálcio com carbonato de cálcio é necessária para o controle da hipocalcemia. A melhor forma de ingestão de carbonato de cálcio ainda é desconhecida, seja concomitante com alimentação, no suco ou em jejum. Objetivo: Avaliar os níveis séricos de cálcio, fósforo e produto cálcio-fósforo em mulheres pós-tireoidectomia por hipoparatireoidismo, após a ingestão de carbonato de cálcio em três formas diferentes. Método: Foi realizado um estudo cruzado em pacientes com hipoparatireoidismo definitivo, avaliados em diferentes situações (em jejum, com água, suco de laranja, café da manhã, após washout de uma semana). A revisão dos prontuários dos pacientes de um hospital terciário de 1994 a 2010 identificou 12 mulheres adultas (18-50 anos), diagnosticadas com hipoparatireoidismo definitivo pós-tireoidectomia. Os resultados laboratoriais dos níveis séricos de cálcio e fósforo foram mensurados antes e a cada 30 minutos durante 5 horas, após a ingestão de carbonato de cálcio (cálcio elementar 500 mg). Resultados: Os valores de pico máximo médio de cálcio, fósforo e produto cálcio-fósforo foram 8,63 mg/dL (água), 8,77 mg/dL (suco de laranja) e 8,95 mg/dL (café da manhã); 4,04 mg/dL (água), 4,03 mg/dL (suco de laranja) e 4,12 mg/dL (café da manhã); 34,3 mg2/dL2 (água), 35,8 mg2/dL2 (suco de laranja) e 34,5 mg2/dL2 (café da manhã), respectivamente, e a área sob a curva foi 2.433 mg/dL.min. (água), 2.577 mg/dL.min. (suco de laranja) e 2.506 mg/dL.min. (café da manhã), 1.203 mg/dL.min. (água), 1.052 mg/dL.min. (suco de laranja) e 1.128 mg/dL.min. (café da manhã), respectivamente. Não houve diferença significante entre os três diferentes testes (p > 0,05). Conclusão: Os níveis séricos de cálcio, fósforo e produto cálcio-fósforo evoluíram de forma semelhante nas três formas de ingestão de carbonato de cálcio.

Ex vivo detection of calcium phosphate and calcium carbonate in rat blood serum.

The total calcium (tCa) in blood serum comprises free Ca2+ ions (fCa), protein-bound calcium (prCa), and complexed calcium by small anions (cCa). The cCa fraction, in addition to fCa, has been indicated to have some physiological activity. However, there is little evidence for the structure of its constituents. Here we report an ex vivo detection of the cCa constituents by synchrotron X-ray absorption near-edge structure spectroscopy. We collected the data directly on rat blood serum and, by making use of the reference samples, derived a spectrum that exhibits the features of cCa constituents. Among the features are those of the complexes of calcium phosphate and calcium carbonate. The detected complexes in the cCa fraction are mainly Ca(η2-HPO4)(H2O)4 and Ca(η1-HCO3)(H2O)5+, in which HPO42- and HCO3- serve as bidentate and unidentate ligands, respectively. The remained H2O molecules on the coordination sphere of Ca2+ enable these complexes to behave partially like aquated Ca2+ ions in protein-binding. Besides, as the dominant part of prCa, albumin-bound calcium (albCa) exhibits a spectrum that closely resembles that of fCa, indicating weak interactions between the protein carboxyl groups and calcium. The weak-bound cCa and albCa, along with fCa and the relevant anions, compose a local chemical system that could play a role in maintaining the calcium level in blood.

Hypoparathyroidism: what is the best calcium carbonate supplementation intake form?

INTRODUCTION: In hypoparathyroidism, calcium supplementation using calcium carbonate is necessary for the hypocalcemia control. The best calcium carbonate intake form is unknown, be it associated with feeding, juice or in fasting. OBJECTIVE: The objective was to evaluate the calcium, phosphorus and calcium×phosphorus product serum levels of hypoparathyroidism women after total thyroidectomy, following calcium carbonate intake in three different forms. METHODS: A crossover study was carried out with patients presenting definitive hypoparathyroidism, assessed in different situations (fasting, with water, orange juice, breakfast with a one-week washout). Through the review of clinical data records of tertiary hospital patients from 1994 to 2010, 12 adult women (18-50 years old) were identified and diagnosed with definitive post-thyroidectomy hypoparathyroidism. The laboratory results of calcium and phosphorus serum levels dosed before and every 30min were assessed, for 5h, after calcium carbonate intake (elementary calcium 500mg). RESULTS: The maximum peak average values for calcium, phosphorus and calcium×phosphorus product were 8.63mg/dL (water), 8.77mg/dL (orange juice) and 8.95mg/dL (breakfast); 4.04mg/dL (water), 4.03mg/dL (orange juice) and 4.12mg/dL (breakfast); 34.3mg2/dL2 (water), 35.8mg2/dL2 (orange juice) and 34.5mg2/dL2 (breakfast), respectively, and the area under the curve 2433mg/dLmin (water), 2577mg/dLmin (orange juice) and 2506mg/dLmin (breakfast), 1203mg/dLmin (water), 1052mg/dLmin (orange juice) and 1128mg/dLmin (breakfast), respectively. There was no significant difference among the three different tests (p>0.05). CONCLUSION: The calcium, phosphorus and calcium×phosphorus product serum levels evolved in a similar fashion in the three calcium carbonate intake forms.

Vitamin D and Calcium Attenuate Bone Loss With Antiretroviral Therapy Initiation: A Randomized Trial.

BACKGROUND: Antiretroviral therapy initiation for HIV-1 infection is associated with 2% to 6% loss of bone mineral density (BMD). OBJECTIVE: To evaluate the effect of vitamin D3 plus calcium supplementation on bone loss associated with antiretroviral therapy initiation. DESIGN: 48-week prospective, randomized, double-blind, placebo-controlled study. (ClinicalTrials.gov: NCT01403051). SETTING: 39 AIDS Clinical Trials Group units. PATIENTS: Adults with antiretroviral therapy-naive HIV. MEASUREMENTS: BMD by dual-energy x-ray absorptiometry, 25-hydroxyvitamin D levels, and other laboratory assessments. RESULTS: 165 eligible patients were randomly assigned (79 received vitamin D3 plus calcium and 86 received placebo). The study groups were well-balanced at baseline: 90% were men, 33% were non-Hispanic black, and the median CD4 count was 0.341 × 109 cells/L. At 48 weeks, the percentage of decline in total hip BMD was smaller in the vitamin D3 plus calcium group than in the placebo group: Medians were -1.36% (interquartile range [IQR], -3.43% to 0.50%) and -3.22% (IQR, -5.56% to -0.88%), respectively (P = 0.004). Similar results were seen at the lumbar spine. At 48 weeks, 90% of patients achieved HIV-1 RNA levels less than 50 copies/mL. Levels of 25-hydroxyvitamin D3 increased with vitamin D3 plus calcium but not with placebo: Median change was 61.2 nmol/L (IQR, 36.4 to 94.3) versus 1.7 nmol/L (IQR, -13.2 to 10.7) (P < 0.001). Overall, 103 patients (62%) reported 1 or more adverse event, with similar distribution between groups; no cases of hypercalcemia and 1 case of nephrolithiasis were reported in the placebo group. LIMITATION: No international sites were included, and follow-up was only 48 weeks. CONCLUSION: Vitamin D3 plus calcium supplementation mitigates the BMD loss seen with initiation of efavirenz/emtricitabine/tenofovir disoproxil fumarate.

Restoration of parathyroid function after change of phosphate binder from calcium carbonate to lanthanum carbonate in hemodialysis patients with suppressed serum parathyroid hormone.

Control of phosphate is the most critical in the treatment of chronic kidney disease with mineral and bone disorder (CKD-MBD). Because calcium-containing phosphate binder to CKD patients is known to induce adynamic bone disease with ectopic calcification by increasing calcium load, we examined the effect of lanthanum carbonate (LaC), a non-calcium containing phosphate binder, to restore bone turnover in 27 hemodialysis patients with suppressed parathyroid function (serum intact parathyroid hormone [iPTH] ≦ 150 pg/mL). At the initiation of LaC administration, the dose of calcium-containing phosphate binder calcium carbonate (CaC) was withdrawn or reduced based on serum phosphate. After initiation of LaC administration, serum calcium and phosphate decreased significantly by 4 weeks, whereas whole PTH and iPTH increased. A significant and positive correlation between decreases of serum calcium, but not phosphate, with increases of whole PTH and iPTH, suggested that the decline in serum calcium with reduction of calcium load by LaC might increase parathyroid function. Serum bone resorption markers, such as serum tartrate-resistant acid phosphatase 5b, and N-telopeptide of type I collagen increased significantly by 4 weeks after LaC administration, which was followed by increases of serum bone formation markers including serum bone alkaline phosphatase, intact procollagen N-propeptide, and osteocalcin. Therefore, it was suggested that LaC attenuated CaC-induced suppression of parathyroid function and bone turnover by decreasing calcium load. In conclusion, replacement of CaC with LaC, either partially or totally, could increase parathyroid function and resultant bone turnover in hemodialysis patients with serum iPTH ≦ 150 pg/mL.

Acute and 3-month effects of microcrystalline hydroxyapatite, calcium citrate and calcium carbonate on serum calcium and markers of bone turnover: a randomised controlled trial in postmenopausal women.

Ca supplements are used for bone health; however, they have been associated with increased cardiovascular risk, which may relate to their acute effects on serum Ca concentrations. Microcrystalline hydroxyapatite (MCH) could affect serum Ca concentrations less than conventional Ca supplements, but its effects on bone turnover are unclear. In the present study, we compared the acute and 3-month effects of MCH with conventional Ca supplements on concentrations of serum Ca, phosphate, parathyroid hormone and bone turnover markers. We randomised 100 women (mean age 71 years) to 1 g/d of Ca as citrate or carbonate (citrate-carbonate), one of two MCH preparations, or a placebo. Blood was sampled for 8 h after the first dose, and after 3 months of daily supplementation. To determine whether the acute effects changed over time, eight participants assigned to the citrate dose repeated 8 h of blood sampling at 3 months. There were no differences between the citrate and carbonate groups, or between the two MCH groups, so their results were pooled. The citrate-carbonate dose increased ionised and total Ca concentrations for up to 8 h, and this was not diminished after 3 months. MCH increased ionised Ca concentrations less than the citrate-carbonate dose; however, it raised the concentrations of phosphate and the Ca-phosphate product. The citrate-carbonate and MCH doses produced comparable decreases in bone resorption (measured as serum C-telopeptide (CTX)) over 8 h and bone turnover (CTX and procollagen type-I N-terminal propeptide) at 3 months. These findings suggest that Ca preparations, in general, produce repeated sustained increases in serum Ca concentrations after ingestion of each dose and that Ca supplements with smaller effects on serum Ca concentrations may have equivalent efficacy in suppressing bone turnover.

Calcium absorption response to cholecalciferol supplementation in hemodialysis.

BACKGROUND AND OBJECTIVES: Recent understanding of extrarenal production of calcitriol has led to the use of more vitamin D supplementation in CKD populations. This paper reports the effect of cholecalciferol supplementation on calcium absorption. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Paired calcium absorption tests were done before and after 12-13 weeks of 20,000 IU weekly cholecalciferol supplementation in 30 participants with stage 5 CKD on hemodialysis. The study was conducted from April to December of 2011. Calcium absorption was tested with a standardized meal containing 300 mg calcium carbonate intrinsically labeled with (45)Ca; 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured. RESULTS: 25-Hydroxyvitamin D rose from 14.2 ng/ml (11.5-18.5) at baseline to 49.3 ng/ml (42.3-58.1) at the end of the study (P<0.001). 1,25-Dihydroxyvitamin D rose from 15.1 (10.5-18.8) pg/ml at baseline to 20.5 (17.0-24.7) pg/ml at the end of the study (P<0.001). The median baseline calcium absorption was 12% (7%-17%) and 12% (7%-16%) at the end of study. CONCLUSIONS: Patients with stage 5 CKD on hemodialysis had very low calcium absorption values at baseline, and cholecalciferol supplementation that raised 25(OH)D levels to 50 ng/ml had no effect on calcium absorption.

Hemoglobin-based oxygen carrier microparticles: synthesis, properties, and in vitro and in vivo investigations.

Bovine hemoglobin microparticles (Hb-MPs) as suitable oxygen carriers are fabricated easily by three key steps: coprecipitation of Hb and CaCO(3) to make Hb-CaCO(3)-microparticles (Hb-CaCO(3)-MPs), cross-linking by glutaraldehyde (GA) to polymerize the Hb and dissolution of CaCO(3) template to obtain pure Hb-MPs. The Hb entrapment efficiency ranged from 8 to 50% corresponding to a hemoglobin quantity per Hb-MP of at least one-third of that in one erythrocyte. The Hb-MPs are spherical, with an average diameter of 3.2 µm and high oxygen affinity. The methemoglobin level was increased after preparation, but can be reduced to less than 7% with ascorbic acid. Phagocytosis assays showed low immunogenicity of Hb-MPs if the particles were cross-linked with low concentration of GA and treated with sodium borohydride. Magnetite-loaded Hb-MPs circulated up to 4 days after intravenous application.

Effect of short-term ornithine alpha-ketoglutarate pretreatment on intestinal ischemia-reperfusion in rats.

PURPOSE: To investigate the effects of preventive enteral administration of ornithine alpha-ketoglutarate (OKG) in an ischemia-reperfusion rat model. METHODS: Sixty rats were randomized into five groups (G1-G5, n = 12). Each group was divided into two subgroups (n = 6) and treated with calcium carbonate (CaCa) or OKG by gavage. Thirty minutes later, the animals were anesthetized with xylazine 15mg + ketamine 1mg ip and subjected to laparotomy. G1-G3 rats served as controls. Rats in groups G4 and G5 were subjected to ischemia for 30 minutes. Ischemia was achieved by clamping the small intestine and its mesentery, delimiting a segment of bowel 5 cm long and 5 cm apart from the ileocecal valve. In addition, G5 rats underwent reperfusion for 30 minutes. Blood samples were collected at the end of the laparotomy (G1), after 30 minutes (G2, G4) and 60 minutes (G3, G5) to determine concentrations of metabolites (pyruvate, lactate), creatine phosphokinase (CPK), thiobarbituric acid reactive substances (TBARS) and glutathione (GSH). RESULTS: There was a significant decrease in tissue pyruvate and lactate and plasma CPK levels in OKG-treated rats at the end of reperfusion period. GSH levels did not change significantly in ischemia and reperfusion groups. However, TBARS levels increased significantly (p<0.05) in tissue samples in OKG-treated rats subjected to ischemia for 30 minutes. CONCLUSION: Short-term pretreatment with OKG before induction of I/R decreases tissue damage, increases pyruvate utilization for energy production in the Krebs cycle and does not attenuate the oxidative stress in this animal model.

Effect of short-term ornithine alpha-ketoglutarate pretreatment on intestinal ischemia-reperfusion in rats / Efeitos do pré-tratamento em curto prazo com ornitina alfa-cetoglutarato na isquemia-reperfusão intestinal em ratos

PURPOSE: To investigate the effects of preventive enteral administration of ornithine alpha-ketoglutarate (OKG) in an ischemia-reperfusion rat model. METHODS: Sixty rats were randomized into five groups (G1-G5, n = 12). Each group was divided into two subgroups (n = 6) and treated with calcium carbonate (CaCa) or OKG by gavage. Thirty minutes later, the animals were anesthetized with xylazine 15mg + ketamine 1mg ip and subjected to laparotomy. G1-G3 rats served as controls. Rats in groups G4 and G5 were subjected to ischemia for 30 minutes. Ischemia was achieved by clamping the small intestine and its mesentery, delimiting a segment of bowel 5 cm long and 5 cm apart from the ileocecal valve. In addition, G5 rats underwent reperfusion for 30 minutes. Blood samples were collected at the end of the laparotomy (G1), after 30 minutes (G2, G4) and 60 minutes (G3, G5) to determine concentrations of metabolites (pyruvate, lactate), creatine phosphokinase (CPK), thiobarbituric acid reactive substances (TBARS) and glutathione (GSH). RESULTS: There was a significant decrease in tissue pyruvate and lactate and plasma CPK levels in OKG-treated rats at the end of reperfusion period. GSH levels did not change significantly in ischemia and reperfusion groups. However, TBARS levels increased significantly (p<0.05) in tissue samples in OKG-treated rats subjected to ischemia for 30 minutes. CONCLUSION: Short-term pretreatment with OKG before induction of I/R decreases tissue damage, increases pyruvate utilization for energy production in the Krebs cycle and does not attenuate the oxidative stress in this animal model.

OBJETIVO: Investigar os efeitos da administração enteral preventiva de ornitina alfa-cetoglutarato (OKG) em modelo de isquemia-reperfusão no rato. MÉTODOS: Sessenta ratos foram randomizados em cinco grupos (G1-G5, n=12). Cada grupo foi redistribuído em dois subgrupos (n=6) e tratado com carbonato de cálcio (CaCa) ou OKG por gavagem. Trinta minutos mais tarde, os animais foram anestesiados com xilazina 1mg+cetamina 15mg i.p. e submetidos à laparotomia. Os ratos dos grupos G4-G5 foram submetidos à isquemia por 30 minutos. A isquemia foi obtida por pinçamento do intestino delgado, delimitando um segmento com 5 cm de comprimento e distando 5 cm da válvula ileocecal. O grupo G5 foi submetido à reperfusão por 30 minutos. Amostras de sangue foram coletadas no final da laparotomia (G1), após 30 minutos (G2, G4) e 60 minutos (G3, G5) para determinação das concentrações de metabolitos (piruvato, lactato), creatinofosfoquinase (CPK), substâncias reativas ao ácido tiobarbitúrico (TBARS) e glutationa (GSH). RESULTADOS: Observou-se redução significante (p<0,05) das concentrações de piruvato e lactato, teciduais e CPK plasmático em ratos tratados com OKG, no final do período de reperfusão. Não houve alteração significante nos níveis plasmáticos e teciduais de GSH. Entretanto os níveis de TBARS aumentaram significativamente (p<0,05) em amostras de tecido de ratos tratados com OKG submetido à isquemia por 30 minutos. CONCLUSÃO: o pré-tratamento em curto prazo com OKG antes da indução da I/R diminui a lesão tecidual, aumenta a utilização de piruvato para produção de energia no ciclo de Krebs, mas não atenua o estresse oxidativo neste modelo animal.

Hormone replacement after thyroid and parathyroid surgery.

BACKGROUND: Hypothyroidism and hypocalcemia are common after thyroid and parathyroid surgery. In this article, the authors provide clinically-oriented recommendations to help surgeons, general practitioners, internists, and endocrinologists give their affected patients adequate hormone replacement therapy. METHODS: Selective evaluation of original articles and reviews that were retrieved by a PubMed search over the years 1980 to 2010, as well as of the recommendations of medical societies including the Endocrine Society (USA), the German Society for Endocrinology (Deutsche Gesellschaft für Endokrinologie), and the American and European Thyroid Associations. RESULTS: Important issues in L-thyroxine replacement therapy include: the selection of the hormone preparation (T4 or T4/T3), combination with iodine (yes/no), the definition of therapeutic TSH ranges (particularly after surgery for thyroid cancer), the extent of remaining thyroid tissue after goiter surgery and its significance, underlying diseases, and drug interactions. The major issues in the treatment of postoperative hypoparathyroidism are: the selection of suitable calcium and vitamin D preparations, the definition of therapeutic goals, the treatment of hypercalciuria and hyperphosphatemia, and the option of recombinant parathormone therapy. CONCLUSION: Effective treatment requires an appropriate choice of medication and an understanding of its pharmacokinetics as well as of the possible effects of the patient's underlying disease, comorbidities, and other medications on its absorption and metabolism.

Acute physiological responses of the freshwater snail Elimia flava (Mollusca: Pleuroceridae) to environmental pH and calcium.

The individual and interactive effects of environmental pH (7 [control], 6, 5, and 4) and calcium (0, 5, and 50 mg/L) were studied on hemolymph ions (pH, Ca(2+), total CO(2), Na(+), K(+)) and osmolality in the freshwater snail, Elimia flava, over a 72-h exposure. All hemolymph factors strongly differed with environmental pH. Snails exposed to pH 4 were inactive and experienced more dramatic ionic disturbances than snails at pH 5, 6, and 7, including reduced hemolymph pH, depressed Na(+) concentrations, and increased Ca(2+) and total CO(2) concentrations. There was an initial but transient increase in hemolymph K(+) over the 72 h exposure period. Environmental calcium ameliorated effects of acidification on hemolymph pH and Na(+), reducing the degree of depression in both variables irrespective of environmental pH or exposure time. In a separate experiment, effects of acidification on snail respiration were examined in which VO(2) was measured over 24 h in snails exposed to pH 7 and 4. Exposure to pH 4 caused a 64% reduction in oxygen uptake at 2 h and a maximum reduction (81%) at 11 h. Our results suggest that snails exposed to pH 4 cease interacting with the surrounding medium and use internal stores of CaCO(3) to buffer hemolymph acidification, whereas snails at pH 5 and higher appear to use environmental calcium as a buffer source. These results suggest an important role of environmental calcium in ameliorating the impacts of short-term, sublethal acidification.

Bone mineral density and bone markers in patients with a recent low-energy fracture: effect of 1 y of treatment with calcium and vitamin D.

BACKGROUND: Low-energy fractures of the hip, forearm, shoulder, and spine are known consequences of osteoporosis. OBJECTIVE: We evaluated the effect of 1 y of treatment with calcium and vitamin D on bone mineral density (BMD) and bone markers in patients with a recent low-energy fracture. DESIGN: In a double-blinded design, patients with fracture of the hip (lower-extremity fracture, or LEF) or upper extremity (UEF) were randomly assigned to receive 3000 mg calcium carbonate + 1400 IU cholecalciferol or placebo (200 IU cholecalciferol). BMD of the hip (HBMD) and lumbar spine (LBMD) were evaluated by dual-energy X-ray absorptiometry, and physical performance was assessed by the timed Up & Go test. Serum concentrations of 25-hydroxycholecalciferol, parathyroid hormone (PTH), telepeptide of type I collagen (ICTP), osteocalcin, and N-terminal propeptide of collagen type I were measured. RESULTS: A total of 122 patients were included (84% women; x +/- SD age: 70 +/- 11 y); 68% completed the study. In an intention-to-treat analysis, LBMD increased in the intervention group and decreased in the placebo group, and the difference between the groups was significant after 12 mo: 0.931 +/- 0.211 compared with 0.848 +/- 0.194 (P<0.05). No significant change was shown for HBMD. The effect of treatment was more pronounced in patients aged <70 y. The intervention decreased bone turnover. PTH was significantly lower in the intervention group (P<0.01) for the LEF patients. ICTP and change in LBMD were significantly related to physical performance. CONCLUSIONS: A 1-y intervention with calcium and vitamin D reduced bone turnover, significantly increased BMD in patients younger than 70 y, and decreased bone loss in older patients. The effect of treatment was related to physical performance.

Milk-alkali syndrome in pre-eclamptic pregnancy: report of a patient and evaluation of albumin-corrected calcium in pre-eclamptic pregnancies.

BACKGROUND: First reported in 1923 due to excessive ingestion of milk and bicarbonate for peptic ulcer disease, milk-alkali syndrome nearly disappeared by the 1980s. More recently, however, this syndrome has become a more common cause of hypercalcemia. This increase is likely due to the increased use of calcium carbonate for the prevention and treatment of osteoporosis. Pregnancy likely places women at risk for milk-alkali syndrome due to increased intestinal absorption of calcium. Recommendations for increased oral calcium intake during pregnancy along with frequent use of calcium carbonate for GI symptoms during late pregnancy increase this risk. METHODS: We performed a retrospective chart review of pregnant women with pre-eclampsia, ages 18-35 years, who were admitted for delivery to the University of Oklahoma Health Sciences Center. Serum calcium levels were reviewed and compared with those of an age- and sex-matched control group consisting of 100 non-pregnant women admitted to the same facility. RESULTS: Twenty-nine of the 100 pregnant patients (29%) had an albumin-corrected calcium above normal compared to only six patients (6%) in the control group (P = 18.32, p < 0.0001). The highest corrected serum calcium in the pregnant group was 12.3 mg/dl compared to 10.7 mg/dl in the control group. SUMMARY: Milk-alkali syndrome is not an uncommon cause of hypercalcemia, and pregnancy may predispose women to milk-alkali syndrome as demonstrated by the patient reported. Albumin-corrected calcium is frequently high in women with pre-eclampsia but ionized calcium is not.

Calcium supplementation does not augment bone gain in young women consuming diets moderately low in calcium.

In earlier observational work, the dietary calcium:protein ratio was directly related to bone accrual in healthy postadolescent women. In this study, we sought to test the hypothesis that augmented calcium intake would increase postadolescent skeletal consolidation, using a double-blind, randomized, placebo-controlled design. We recruited 152 healthy young women (age 23.1 +/- 2.7 y, BMI 22.5 +/- 3.0 kg/m2); their usual diets, as assessed by 7-d food diaries, were low in calcium (605 +/- 181 mg/d; 15.1 +/- 4.5 mmol/d) and in the calcium:protein ratio (10.1 +/- 2.0 mg/g). The subjects were randomly assigned to supplemental calcium [500 mg calcium (12.5 mmol) as the carbonate, 3 times/d, with meals] or placebo capsules identical in appearance; all participants also took a daily multivitamin, and they were followed for up to 36 mo with bone densitometry (dual energy X-ray absorptiometry; DXA) at 6-mo intervals. A total of 121 subjects remained in the study for at least 12 mo (median time in the study, 35 mo), with a mean compliance level (observed/expected tablet consumption) of 87.7%. DXA data for these 121 subjects indicated modest but significant mean rates of increase (i.e., 0.24 to 1.10%/y) in bone mineral content (BMC; total body, total hip, and lumbar spine) and in lumbar spine bone mineral density (BMD) but no change in total hip BMD. None of these rates of change differed by group, i.e., calcium supplementation did not have any measurable effect on bone mass accrual. By midstudy, the calcium content of the subjects' usual diets for both groups had risen by approximately 15%. The combined effect of improved intakes of dietary calcium and the small amount of calcium added by the multivitamin tablets resulted in a mean calcium intake for the control group > 800 mg (20 mmol)/d, possibly at or near the threshold beyond which additional calcium has no further effect on bone accrual.

Acute waterborne cadmium uptake in rainbow trout is reduced by dietary calcium carbonate.

The effects of elevated dietary calcium (as CaCO3) and acute waterborne Cd exposure (50 microg/l) on whole body uptake, tissue uptake, and internal distribution of newly accumulated Cd, Ca2+, and Na+ in juvenile rainbow trout were examined. Fish were fed with three diets (mg Ca2+/g food): 20 (control), 30 and 60 for 7 days before fluxes were measured with radiotracers. The highest dietary Ca2+ elevation reduced waterborne whole body Ca2+ uptake, but did not protect against inhibition of waterborne Ca2+ uptake by waterborne Cd. Both Ca2+-supplemented diets reduced newly accumulated Ca2+ in the gills in relation to the control treatment, but did not prevent the Cd-inhibiting effect against accumulation of new Ca2+ in most compartments. Fish fed with Ca2+-supplemented diets showed markedly lower rates of whole body uptake and internalization (in some tissues) of waterborne Cd, illustrating that, while dietary Ca2+ supplementation did not protect against the impact of waterborne Cd on waterborne Ca2+ uptake, it did protect against the uptake of Cd. Waterborne Cd had no effect on Na+ fluxes, total Cl-, and in most body compartments, newly accumulated Na+ and total Na+ were also not affected. Dietary supplementation with CaCO3 had the same protective effect as demonstrated by dietary supplementation with CaCl2 in an earlier study. Thus, the reduction of waterborne Cd uptake and internalization by dietary Ca2+ was specifically due to Ca2+ and not to the anion.