Lack of Awareness of Dietary Sources of Phosphorus Is a Clinical Concern.

Hyperphosphatemia is a serious complication in patients with chronic kidney disease (CKD), and is associated with more rapid progression as well as higher risk of mortality, and higher rate of cardiovascular disease accidents. CKD patients are usually advised to adopt a low phosphate diet in addition to phosphate-lowering medications, if necessary. However, there is a lack of awareness of the dietary sources of phosphate, especially hidden phosphate intake from phosphate additives in processed foods and carbonated beverages. Appropriate nutritional education could be an effective solution in reducing phosphate toxicity without introducing an additional pill burden or malnutrition.

Growth and development of skeletal anomalies in diploid and triploid Atlantic salmon (Salmo salar) fed phosphorus-rich diets with fish meal and hydrolyzed fish protein.

Diploid and triploid Atlantic salmon, Salmo salar were fed high-protein, phosphorus-rich diets (56-60% protein; ca 18g phosphorus kg-1 diet) whilst being reared at low temperature from start-feeding until parr-smolt transformation. Performances of salmon fed diets based on fish meal (STD) or a mix of fishmeal and hydrolysed fish proteins (HFM) as the major protein sources were compared in terms of mortality, diet digestibility, growth and skeletal deformities. Separate groups of diploids and triploids were reared in triplicate tanks (initially 3000 fish per tank; tank biomass ca. 620 g) from 0-2745 degree-days post-start feeding (ddPSF). Growth metrics (weight, length, condition factor) were recorded at ca. 4 week intervals, external signs of deformities to the operculum, jaws and spinal column were examined in parr sampled at 1390 ddPSF, and external signs of deformity and vertebral anomalies (by radiography) were examined in fish sampled at the end of the trial (2745 ddPSF). The triploid salmon generally had a lower mass per unit length, i.e. lower condition factor, throughout the trial, but this did not seem to reflect any consistent dietary or ploidy effects on either dietary digestibility or the growth of the fish. By the end of the trial fish in all treatment groups had achieved a weight of 50+ g, and had completed the parr-smolt transformation. The triploids had slightly, but significantly, fewer vertebrae (Triploids STD 58.74 ± 0.10; HFM 58.68 ± 0.05) than the diploids (Diploids STD 58.97 ± 0.14; HFM 58.89 ± 0.01), and the incidence of skeletal (vertebral) abnormalities was higher in triploids (Triploids STD 31 ± 0.90%; HFM 15 ± 1.44%) than in diploids (Diploids STD 4 ± 0.80%; HFM 4 ± 0.83%). The HFM diet gave a significant reduction in the numbers of triploid salmon with vertebral anomalies in comparison with the triploids fed the STD diet possibly as a result of differences in phosphorus bioavailability between the two diets. Overall, the incidence of skeletal deformities was lower than reported in previous studies (Diploids 20+%, Triploids 40+%), possibly as a result of the combination of rearing at low-temperature and phosphorus-rich diets being used in the present study.

Conhecimento de hiperfosfatemia e quelante de fósforo em hemodialíticos / Knowledge about hyperphosphatemia and phosphate binder at hemodialysis

Introdução: O controle do fósforo sérico é um desafio no tratamento de pacientes em hemodiálise. A orientação dietética e o uso adequado de quelantes são a base do tratamento e seu sucesso depende essencialmente da habilidade do paciente em entender e aderir ao plano dietético e ao uso dos quelantes. Objetivo: Avaliar o conhecimento sobre hiperfosfatemia e uso de quelantes de fósforo de pacientes em hemodiálise. Método: Estudo transversal que avaliou 74 pacientes em hemodiálise, por meio de questionário preestabelecido sobre conhecimento da hiperfosfatemia, uso de quelantes, alimentos ricos em fósforo, e aspectos relacionados ao tratamento da hiperfosfatemia. Os parâmetros laboratoriais Kt/V, níveis séricos de paratormônio (PTH), fósforo (P), cálcio (Ca) e produto cálcio/fósforo (CaxP) foram identificados. Os dados foram apresentados como porcentagens ou média e desvio padrão. Para avaliação dos fatores associados à hiperfosfatemia, utilizou-se a regressão de Poisson, adotando nível de significância adotado de 5%. Resultados: Cerca de 40,3% dos pacientes faziam uso de quelantes de fósforo, 36,6% apresentavam níveis séricos de PTH elevados, 36% de hiperfosfatemia e 28% estavam com o produto Ca x P inadequado. A maioria conhecia os efeitos da hiperfosfatemia (52%) e sua relação causal com a alimentação (82,2%), sendo capazes de identificar os alimentos ricos em fósforo (60%). O uso de quelantes junto às refeições foi apontado por 88% dos pacientes. O insucesso no tratamento da hiperfosfatemia foi atribuído ao consumo de dieta rica em fósforo por 70,9% dos pacientes. Conclusão: A maioria dos pacientes possuía conhecimento sobre a hiperfosfatemia, contudo, apresentou baixa adesão às recomendações dietéticas.(AU)

Introduction: The control of serum phosphorus is a challenge in the treatment of hemodialysis patients. Dietary guidance and the proper use of chelating agents are the mainstay of treatment, its success depends primarily on the patient's ability to understand and adhere to the dietary plan and the use of chelators. Objective: To assess the knowledge of hyperphosphatemia and use of phosphate binders in hemodialysis patients treated. Methods: A cross-sectional study evaluated 74 patients in hemodialysis, through preestablished questionnaire on knowledge of hyperphosphatemia, use of binders, phosphorus-rich foods, and aspects related to the treatment of hyperphosphatemia. The laboratory parameters Kt / V, serum levels of parathyroid hormone (PTH), phosphorus (P), calcium (Ca) and product calcium / phosphorus (Ca x P) were identified. The data were presented as percentages or means and standard deviations. To evaluate the factors associated with hyperphosphatemia were used Poisson regression, with a level of significance of 5%. Results: About 40.3% of patientes made use of phosphorus binders, 36.6% had elevated serum PTH, 36% of hyperphosphatemia and 28% had inadequate Ca x P product. Most knew the effects of hyperphosphatemia (52%) and their causal relationship with food (82.2%), being able to identify foods rich in phosphorus (60%). The use of binders with meals was reported by 88% of patients. The failure in the treatment of hyperphosphatemia has been attributed to the consumption of a diet rich in phosphorus by 70.9% of patients. Conclusion: Most patients had knowledge of hyperphosphatemia, however showed poor adherence to dietary recommendations.(AU)

Dmp1 Null Mice Develop a Unique Osteoarthritis-like Phenotype.

Patients with hypophosphatemia rickets (including DMP1 mutations) develop severe osteoarthritis (OA), although the mechanism is largely unknown. In this study, we first identified the expression of DMP1 in hypertrophic chondrocytes using immunohistochemistry (IHC) and X-gal analysis of Dmp1-knockout-lacZ-knockin heterozygous mice. Next, we characterized the OA-like phenotype in Dmp1 null mice from 7-week-old to one-year-old using multiple techniques, including X-ray, micro-CT, H&E staining, Goldner staining, scanning electronic microscopy, IHC assays, etc. We found a classical OA-like phenotype in Dmp1 null mice such as articular cartilage degradation, osteophyte formation, and subchondral osteosclerosis. These Dmp1 null mice also developed unique pathological changes, including a biphasic change in their articular cartilage from the initial expansion of hypertrophic chondrocytes at the age of 1-month to a quick diminished articular cartilage layer at the age of 3-months. Further, these null mice displayed severe enlarged knees and poorly formed bone with an expanded osteoid area. To address whether DMP1 plays a direct role in the articular cartilage, we deleted Dmp1 specifically in hypertrophic chondrocytes by crossing the Dmp1-loxP mice with Col X Cre mice. Interestingly, these conditional knockout mice didn't display notable defects in either the articular cartilage or the growth plate. Because of the hypophosphatemia remained in the entire life span of the Dmp1 null mice, we also investigated whether a high phosphate diet would improve the OA-like phenotype. A 8-week treatment of a high phosphate diet significantly rescued the OA-like defect in Dmp1 null mice, supporting the critical role of phosphate homeostasis in maintaining the healthy joint morphology and function. Taken together, this study demonstrates a unique OA-like phenotype in Dmp1 null mice, but a lack of the direct impact of DMP1 on chondrogenesis. Instead, the regulation of phosphate homeostasis by DMP1 via the axis of "FGF23-renal phosphorus reabsorption" is vital for maintaining a healthy joint.

Neuromuscular signs associated with acute hypophosphatemia in a dog.

The purpose of this report was to describe the successful recognition and management of neuromuscular dysfunction secondary to severe, acute hypophosphatemia in an adult dog with a 2 day history of vomiting, anorexia, and abdominal pain. Radiographs were suggestive of a foreign body obstruction, and surgery was recommended. Resection and anastomosis of the distal duodenum and proximal jejunum was performed. The dog recovered uneventfully, but approximately 36 hr postoperatively, he was found to have significant weakness and muscle tremors that were accompanied by hyperthermia. The only significant abnormality on a serum biochemical profile was a phosphorous level of 0.26 mmol/L. Within 6 hr of initiating phosphorous supplementation, the patient fully recovered and had no residual signs of neuromuscular dysfunction. Signs of neurologic dysfunction secondary to hypophosphatemia are commonly recognized in human patients. Reports of patients with severe muscle weakness, some of which necessitate ventilation due to weakening of muscles of respiration, are common throughout the literature. Less commonly, tremors are noted. This is the first known report of neuromuscular signs recognized and rapidly corrected in a dog. Although it is likely to be uncommon, hypophosphatemia should be recognized as a differential diagnosis in patients with tremors and/or muscle weakness.

Metabolic bone disease of prematurity: report of four cases.

Osteopenia of prematurity has become a common problem recently because of improved survival rates of infants with very low birth weight (VLBW). The incidence of neonatal osteopenia is inversely correlated with gestational age and birth weight. Herein, we present four cases of preterm osteopenia that were referred to the pediatric endocrinology outpatient clinic with diverse clinical and laboratory findings and we discuss the clinical course of these infants with regard to bone disease after discharge from the neonatal intensive care unit (NICU). This report highlights the importance of enteral calcium, phosphorus and vitamin D support at adequate doses following discharge from NICU for preterm infants with VLBW who are at risk of metabolic bone disease.

Dietary phosphorus exacerbates bone loss induced by cadmium in ovariectomized rats.

OBJECTIVE: Postmenopausal bone loss can be exacerbated by environmental contaminants, including the heavy metal cadmium (Cd). We hypothesized that incorporating phosphorus (P) into the diet would lead to the chelation of Cd into P, preventing its absorption and subsequent bone loss. METHODS: To test this hypothesis, we used ovariectomized rats as a model of postmenopausal osteoporosis to examine the deleterious effects of Cd on bone with and without added P. Fifty 3-month-old ovariectomized Sprague-Dawley rats were assigned to five treatment groups (n = 10 per group) for 3 months as follows: (1) control; (2) 50 ppm Cd; (3) 50 ppm Cd plus 1.2% P; (4) 200 ppm Cd; and (5) 200 ppm Cd plus 1.2% P. RESULTS: Cd plus P caused a significant loss of whole body (P = 0.0001 and P < 0.001) and femoral (P = 0.0005 and P < 0.001) bone mineral density (BMD) and bone mineral content, respectively, and a loss of fourth lumbar vertebra BMD and bone mineral content (P < 0.0001 and P < 0.001, respectively). Nonetheless, 200 ppm Cd plus 1.2% P had the most deleterious effects on whole body and femoral BMD. For femoral neck microstructural properties, 50 ppm Cd plus 1.2% P caused an increase in trabecular separation, whereas 200 ppm Cd plus 1.2% P caused a decrease in bone volume-to-total volume ratio, a decrease in trabecular number, and an increase in trabecular separation and structural model index. CONCLUSIONS: Our findings indicate that Cd exposure, along with high intake of P, may be a public health hazard with respect to bone health.

Hyperphosphatemia and phosphate binders: effectiveness and safety.

In patients with kidney dysfunction hyperphosphatemia is more evident as renal failure progresses. It is related to increased FGF-23 levels, secondary hyperparathyroidism, and accelerated progressive vascular calcification. In CKD patients advanced coronary artery calcification is strongly associated with future cardiovascular events, cardiovascular death, and all-cause mortality. Apart from the above, phosphate per se is suspected as a causal risk factor for CKD progression. Keeping serum phosphorus within the target values are linked to improvement in life expectancy. A low phosphate diet, an efficient dialysis removal of phosphate load, and the administration of phosphate binders are the main recommended steps to control hyperphosphatemia. Calcium-based phosphate binders can lead to a positive calcium balance, hypercalcaemia, parathyroid gland suppression, adynamic bone disease, and coronary artery and aortic calcification. On the other hand Sevelamer hydrochloride and Lanthanum carbonate has been shown to be effective, safe and useful therapeutic tools for hyperphosphatemia. When prescribe pharmacological agents, one must take into account the large increase in health-care expenditure and the choice of phosphate binder should be individualized.

Association of a reduction in central obesity and phosphorus intake with changes in urinary albumin excretion: the PREMIER study.

BACKGROUND: Excess adiposity and dietary factors may be important determinants of urinary albumin excretion (UAE). STUDY DESIGN: Observational analysis of PREMIER, a randomized trial designed to lower blood pressure using behavioral interventions (counseling on weight loss, healthy diet, and exercise). SETTING & PARTICIPANTS: 481 participants with normal kidney function who provided adequate 24-hour urine collections at baseline and 6 months. PREDICTORS: Change in waist circumference; 24-hour urine sodium, potassium, and phosphorus excretion; and protein intake estimated from urea nitrogen. OUTCOMES & MEASUREMENTS: The primary outcome was change in log-transformed 24-hour UAE over 6 months. RESULTS: After 6 months, the proportion of individuals with UAE ≥10 mg/d decreased from 18.7% to 12.7% (P < 0.001). Changes in mean waist circumference (-4.2 ± 6.6 [SD] cm), 24-hour excretion of sodium (-28.2 ± 71.7 mmol/d), potassium (+8.4 ± 27.8 mmol/d), phosphorus (-27.7 ± 314.1 mg/d), and protein intake (-1.7 ± 19.4 g/d) were observed. After adjustment for relevant covariates, the following variables were associated significantly with reduction in ln(UAE) in separate models: decrease in waist circumference (P = 0.001), decrease in 24-hour urine phosphorus excretion (P < 0.001), and decrease in protein intake (P = 0.01). In a multivariable model including these 3 predictors, decreases in waist circumference (P = 0.002) and 24-hour urine phosphorus excretion (P = 0.03), but not change in protein intake (P = 0.5), remained associated significantly with reduction in ln(UAE). These associations remained significant even after adjustment for changes in blood pressure and insulin resistance. Baseline UAE and metabolic syndrome modified the relationship of waist circumference with ln(UAE); specifically, individuals with higher UAE and baseline metabolic syndrome experienced greater reductions in ln(UAE) from decreases in waist circumference. LIMITATIONS: Observational study with potential for confounding. CONCLUSIONS: In adults with normal kidney function, decreases in waist circumference and 24-hour urine phosphorus excretion are associated with reductions in UAE. These findings support the rationale for clinical trials to determine whether reducing dietary phosphorus intake or waist circumference could prevent chronic kidney disease or slow its progression.

Studies on "stiffness of extremities disease" in the yak (Bos mutus).

Wild yak (Bos mutus) are affected by a disorder known colloquially as "stiffness of extremities disease," characterized by emaciation, lameness, stiffness in the gait, enlargement of the costochondral junctions, and abnormal curvature in the long bones. Results from preliminary epidemiologic and clinical observations suggested that this was a local, nutritional and metabolic disease associated with some mineral deficiency. Our objective was to determine the possible relationship between this disease and phosphorus (P) deficiency. We found that P concentrations in forage samples from affected areas were significantly lower than were those from unaffected areas, and the mean calcium:P ratio in the affected forage was 14:1. Phosphorus concentrations of blood, bone, teeth, and hair from affected yak were also significantly lower than were those from reference yak. Serum P levels of affected animals were much lower than were those of reference yak, whereas serum alkaline phosphatase levels were significantly higher than were those from reference yak. The P deficiency disease could be cured with supplement of disodium hydrogen phosphate (Na(2)HPO(4)). We conclude that the disease is mainly caused by P deficiency in forage.

VDR deficiency affects alveolar bone and cementum apposition in mice.

OBJECTIVE: To compare the mineralisation density (MD), morphology and histology of alveolar bone and cementum amongst VDR +/+, VDR -/-, and VDR -/- groups supplemented with a diet TD 96348, containing 20% lactose, 2.0% calcium and 1.25% phosphorous. METHODS: Four groups of mice (6 mice/group) were identified by genotyping: VDR +/+ mice (VDR wild type), VDR -/- mice (VDR deficient), VDR -/- offsprings derived from VDR -/- parents receiving a supplemental diet (early rescued), and VDR -/- mice fed with a supplemental diet beginning at age one month (late rescued). All mice were sacrificed at age 70.5 days. Micro-CT was used to compare MD and morphology of alveolar bone and cementum. H-E and Toluidine blue staining was used to examine the ultrastructure of the alveolar bone and cementum at matched locations. RESULTS: In VDR -/- group, alveolar bone and cementum failed to mineralise normally. Early rescue increased MD of alveolar bone in VDR -/- mice with excessive alveolar bone formation, but which not observed in late rescue group. MD and morphology of cementum-dentine complex in both early and late rescue groups were comparable with VDR +/+ group when feeding with high-calcium rescue diet. CONCLUSIONS: VDR affects alveolar bone mineralisation and formation systemically and locally. However, cementum apposition and mineralisation is mainly regulated by calcium concentrations in serum.

Physiopathology of dental rickets in vitamin D receptor-ablated mice.

1α25(OH)(2)vitaminD(3) and its nuclear receptor, VDR, are essential for normal tooth development. However, the relative contributions of the direct vs. indirect effects of vitamin D action on odontogenesis are unclear. The aim of this study was to discriminate among the specific roles of 1α25(OH)(2) vitaminD(3), calcemia/phosphatemia, and the maternal environment in mouse VDR null mutants. Microradiographic, histological, and molecular analyses were conducted on adult mice under hypocalcemic/hypophosphatemic vs. normocalcemic/normophosphatemic conditions, and pups of first- (VDR-/- born to VDR+/- dams) vs. second-generation (VDR-/- born to VDR-/- dams) mice. In VDR-/- mice, crown morphogenesis was affected exclusively in second-generation pups. In first-generation adult VDR-/- mice, both enamel and dentin were affected, and pathologic features of root resorption in both apical and cervical regions were observed. Nutritional calcium and phosphate normalization completely rescued the root resorption and partially rescued the dentin and enamel phenotypes (altered cell differentiation and matrix protein expression). Analysis of these data illustrates the co-existence of different pathways of vitamin D action in tooth differentiation and biomineralization. These targeted and cumulative effects would generate the diverse and wide spectrum of dental rickets phenotypes.

Dietary magnesium supplementation suppresses bone resorption via inhibition of parathyroid hormone secretion in rats fed a high-phosphorus diet.

This study examined the effects of dietary magnesium (Mg) supplementation on bone turnover and serum parathyroid hormone (PTH) levels in rats fed a high-phosphorus (P) diet. Male rats were randomized by weight into three groups, and fed a control diet (control), a high-P diet (HP) or a high-P and high-Mg diet (HPHMg) for 14 days. Serum osteocalcin levels were significantly higher in the HP and HPHMg groups than in the control group. Serum CTx levels were significantly higher in the HP and HPHMg groups than in the control group, while the levels in the HPHMg group were significantly lower than in the HP group. Serum PTH levels were significantly higher in the HP group than in the control and HPHMg groups. Dietary Mg supplementation had a significant influence on serum PTH levels in the HP and HPHMg groups. These results suggest that dietary Mg supplementation suppresses the high bone resorption induced by a high-P diet via inhibition of PTH secretion. Moreover, our results suggest that dietary Mg supplementation may be beneficial for the prevention of bone loss with high-P diet administration.

Ironing out the phosphorus problem.

Control of serum phosphorus remains a vexing problem in chronic kidney disease. Although novel dialysis regimens may provide excellent phosphorus control, phosphate binders remain necessary for most dialysis patients. Block et al. present a phase I clinical trial examining the safety and efficacy of SBR759, a novel non-calcium, iron-based phosphate binder. Although the risks of iron accumulation and hypocalcemia must be addressed, this phosphate binder appears to be well tolerated and effective and offers a powder-based formulation.

Effects of reduced calcium and phosphorous diets supplemented with phytase on laying performance of hens.

The aim of this experiment was to examine the potential for reduced environmental impact by reducing dietary calcium and phosphorus content and phytase addition of laying hen diets. A randomized complete block design with a 2x2x2 factorial arrangement of 8 dietary treatments: 2 levels ofphytase (0 and 300 FTU kg(-1)) and 2 mineral levels (Ca: 34/18 and NPP: 3.2/2.2 g kg(-1), respectively). A total of 240 White Leghorn (WL) layers, 25 weeks of age were used. Considering birds in 12 cages as a replicate, 5 such replicates were randomly allotted to each dietary treatment. Individual body weight of the bird was recorded at the beginning and end of the experiment. Egg production on an individual basis was recorded daily and percentage hen day egg production was calculated. The cleaned eggshells were dried for 24 h, weighed and expressed as percentage of whole egg. One bird from each experimental unit were selected at random and killed by cervical dislocation at the end of the experiment and the left tibia was removed. Dried bone samples were ashed at 680 degrees C for 12 h for estimation of bone ash. The results of this experiment showed that reducing Ca and NPP (Non-Phytate Phosphorus) without phytase decreased BWG (Body Weight Gain), feed intake, FCE (Feed Conversion Efficiency), egg production, egg shell weight and tibia ash. However, phytase addition to low mineral diets completely corrected the adverse effects associated with low dietary Ca and NPP. It can therefore be concluded that reducing levels of Ca and NPP below current standards and phytase supplementation can reduce pollution potential from laying hen production without adversely affecting bird performance or welfare.

A novel mutation of the GLUT2 gene in a Turkish patient with Fanconi-Bickel syndrome.

Fanconi-Bickel syndrome is a rare inherited disorder of carbohydrate metabolism. The disease is characterized by the association of a massive hepatomegaly due to glycogen accumulation, severe hypophosphatemic rickets and marked growth retardation due to proximal renal tubular dysfunction. Fanconi-Bickel syndrome is a single gene disease and is caused by defects in the facilitative glucose transporter 2 (GLUT2) gene (SLC2A2) on chromosome 3q26.1-26.3, which encodes for the glucose transporter protein 2 expressed in hepatocytes, pancreatic beta-cells, enterocytes, and renal tubular cells. Several mutations in a gene encoding a glucose transporter have been reported in patients with Fanconi-Bickel syndrome. Here we report a Turkish child who had a novel mutation that has not been described before and we discuss the knowledge regarding genetic mutations in this rare disease.

Enteral calcium, phosphate and vitamin D requirements and bone mineralization in preterm infants.

UNLABELLED: With major advances in life-support measures, nutrition has become one of the most debated issues in the care of very low birth-weight (VLBW) infants. Current nutritional recommendations are based on healthy premature infants and designed to provide postnatal nutrient retention during the 'stable-growing' period equivalent to the intrauterine gain of a normal foetus. However, this reference is still a matter of discussion, especially in the field of the mineral requirements. After birth, there are dramatic physiological changes in bone metabolism resulting from various factors: disruption in maternal mineral supply, stimulation of calciotropic hormone secretion, change in hormonal environment and relative reduction in mechanical stress. These events stimulate the remodelling process leading to an increase in endosteal bone resorption and a decrease in bone density. In preterm infants, these adaptation processes modify the mineral requirement, since, by itself, the increased remodelling provides a part of the mineral requirement necessary for postnatal bone growth and turnover. The care of newly born premature infants should not necessarily aim to achieve intrauterine calcium accretion rates. CONCLUSION: Considering that a calcium retention level ranging from 60 to 90 mg/kg/day assures appropriate mineralization, and decreases the risk of fracture and diminishes the clinical symptoms of osteopenia, an intake of 100 to 160 mg/kg/day of highly bioavailable calcium salts, 60 to 90 mg/kg/day of phosphorus and 800 to 1000 IU of vitamin D per day is recommended.

Dietary-related skeletal changes in a Shetland sheepdog puppy.

A commercially available, renal failure diet was used to manage suspected renal failure in a 10-week-old Shetland sheepdog puppy. Rickets subsequently developed, possibly from low phosphorous intake and an increased calcium to phosphorus ratio. Decreased dietary calcium in addition to decreased phosphorus may have played a role in decreasing bone mineral density. Lethargy, decreased long bone growth, angular limb deformity, and osteopenia occurred, but these signs resolved within 3 months with nutritional management.