Osteomalacia as a result of phosphorus deficiency in beef cattle grazing subtropical native pastures in Uruguay.

We investigated 2 outbreaks of osteomalacia as a result of phosphorus (P) deficiency in herds of lactating beef cows grazing subtropical native pastures in Uruguay. Cows exhibited pica, difficulty to stand and walk, rib fractures, and body weight loss even with adequate forage availability. Osteopenia and severe osteomalacia were observed on gross and histologic examination. The concentrations of bicarbonate-extractable P in soil (4.0, 4.1 mg P/kg), total P in pasture (0.9, 1.1 g P/kg), inorganic P in serum (1.0, 0.71 mmol P/L), and P in bone (73 mg P/mL) were all low. Although injectable and mineral salt supplements provided additional P in both outbreaks, these supplementary amounts were insufficient to prevent P deficiency. The P ingested by the cows from the pasture and supplements would have provided 20-55% of their daily P requirements of ~21 g P/d. Osteomalacia occurred in cattle at the 2 ranches as a result of severe P deficiency in the soil and forage, and inadequate P supplementation. Following diagnosis, control of P deficiency in beef cattle requires estimation of the amount of pasture P ingested and provision of sufficient additional supplementary P to meet the animals' requirements.

Bone mineral density and serum levels of 25 OH vitamin D in chronic users of antiepileptic drugs.

The aim of this cross sectional study was to evaluate bone mineral density (BMD) and serum levels of 25-hydroxy vitamin D (25OHD) in a group of patients taking antiepileptic drugs (AED) for a seizure disorder. Between May-2001 and January-2003, we evaluated 58 patients (40 women/18 men), 34.4+/-6 years old living in Curitiba or in its metropolitan area, on antiepileptic therapy for 2 to 38 years (10 on monotherapy /48 on multiple drugs regime). The group was matched by age, gender, and bone mass index to 29 healthy subjects (20 women/ 9 men); 34.2+/-5.9 years old. Medical history and physical exam were performed on all subjects with particular information sought about fractures and risks factors for osteoporosis. Blood samples were collected for total serum calcium, albumin, phosphorus, creatinine, total alkaline phosphatase, and liver function tests. BMD of the lumbar spine, femur and forearm was determined by dual energy X-ray absorptiometry (DXA, Hologic QDR 1000). Between February and April-2003, other blood samples were collected to measure 25OHD, intact paratohormone (PTH) and calcium. Unemployment and smoking history were more frequent among patients than among controls (p<0.05). Fifteen patients had a fracture history, all of which occurred during a seizure. The BMD of the lumbar spine (0.975+/-0. 13 g/cm2 vs. 1.058+/-0.1 g/cm2; p<0.03) and of the total femur (0.930+/-0.1 g/cm2 vs. 0.988+/-0.12 g/cm2; p<0.02) was lower in patients than in controls. In 63.5% of patients and in 24.1 % of controls a T-score < -1.0 in at least one site was seen. The AED users had higher total alkaline phosphatase and lower 25OHD (p<0.02). No correlations between BMD and 25OHD were found. The use of phenytoin was correlated with a greater incidence of fractures (RR: 2.38). We conclude that patients on chronic use of AED have alterations in bone metabolism characterized in this study by lower BMD of the lumbar spine and total femur and lower serum concentrations of 25OHD.

Bone mineral density and serum levels of 25 OH vitamin D in chronic users of antiepileptic drugs

O objetivo deste estudo transversal foi avaliar a densidade mineral óssea (DMO) e os níveis de 25hidroxi vitamina D (25OHD) em um grupo de pacientes com epilepsia e usuários crônicos de drogas antiepilépticas (DAE). Entre maio-2001 e janeiro-2003 avaliamos 58 pacientes (40 mulheres/18 homens) residentes em Curitiba ou região metropolitana da cidade, com média de idade 34,4±6 anos e tempo de tratamento entre 2 e 38 anos (10 em monoterapia/48 em politerapia). O grupo de pacientes foi emparelhado por idade, sexo e índice de massa corpórea com 29 indivíduos aparentemente sadios (20 mulheres/9 homens; 34,2±5,9 anos). Pacientes e controles foram submetidos a anamnese e exame clínico, com ênfase na história de fraturas e fatores de risco para osteoporose. Nas visitas foram coletadas amostras de sangue para dosagens de cálcio, albumina, fósforo, creatinina, fosfatase alcalina, transaminases e gama GT. Foi avaliada também a DMO na coluna lombar, fêmur e antebraço (DEXA, Hologic QDRW1000®). Entre fevereiro e abril-2003, pacientes e controles foram chamados para nova coleta de sangue para dosagem da 25OHD e parato-hormônio (PTH) intact. Desemprego e tabagismo foram mais comuns nos pacientes do que nos controles (p<0,05). Quinze pacientes relataram fraturas durante as crises epilépticas. A DMO da coluna lombar (0,975±0,13 g/cm2 vs 1,058±0,1 g/cm2; p<0,03) e do fêmur total (0,930±0,1 g/cm2 vs 0,988±0,12 g/cm2; p<0,02) foi menor nos pacientes do que controles. Em 63,5% dos pacientes e em 24,1% dos controles foi registrado escore T < -1.0 desvio-padrão em pelo menos um dos sítios avaliados. Os usuários crônicos de DAE apresentaram níveis de fosfatase alcalina mais elevados (p<0,01) e níveis de 25OHD mais baixos (p<0,02 vs controles). Não houve correlação entre a DMO e os níveis de 25OHD. O uso de fenitoína correlacionou-se positivamente com maior incidência de fraturas (RR: 2,38). Concluímos que usuários crônicos de DAE apresentam importantes alterações do metabolismo mineral ósseo, demonstrada no presente estudo através de valores menores da DMO em coluna lombar e fêmur e níveis séricos diminuídos de 25OHD.

[Effect of strontium on bone metabolism in hemodialysis patients]. / Efecto del estroncio sobre el metabolismo óseo en pacientes en hemodiálisis.

The objective of this study was to assess the relationship between the bone strontium content and bone histomorphometric parameters in bone biopsies from patients with chronic renal failure undergoing hemodialysis. The study was carried out in 74 illiac crest bone biopsies from patients with renal osteodystrophy from different worldwide regions (Argentina, Portugal and Spain). They were underwent to histological and histomorphometric evaluation. The bone strontium/calcium ratio was measured by quadrupole inductively coupled plasma-mass spectrometry. The samples were classified into groups according to histological criteria: hyperparathyroidism (HP), mixed (MX), osteomalacia (OM) and adynamic bone disease (ABD). Serum PTH and alkaline phosphatase before biopsy were available in most of the patients. No correlation was found between the different histomorphometric parameters and the Sr/Ca ratio. The one way ANOVA test showed statistical differences in the Sr/Ca ratio of the different histological forms (HP: 0.58 +/- 0.39; MX: 1.16 +/- 0.74; OM: 1.10 +/- 0.46; ABD: 0.91 +/- 0.40 microgram Sr/mg Ca; p < 0.003). The post-Hoc analysis showed differences between HP and MX. The biopsies having greater or equal values than 1.4 micrograms Sr/mg Ca showed higher levels of bone formation histomorphometric parameters and serum alkaline phosphatase (395 +/- 519 vs 1,022 +/- 989 UI/L, p < 0.05). Although it has been found that the biopsies with higher bone strontium had higher levels of osteoid tissue (characteristic of osteomalacia), the hypothesis of strontium-induced osteomalacia could not be demonstrated.

Aluminum exposure in chronic renal failure in iberoamerica at the end of the 1990s: overview and perspectives.

Epidemic aluminum neurotoxicity has virtually disappeared in the dialysis population; however, sporadic toxic effects caused by contamination of water with aluminum are still reported. In this review, the current situation in Iberoamerica is analyzed. Exposure to aluminum through dialysate shows considerable geographical differences even within the same country, including seasonal variability. Sometimes the tap water showed very high aluminum content that does not permit the water treatment system to efficiently remove all the aluminum, forcing the use of water treatment systems with a double reverse-osmosis filter on line. The use of adequate water treatment systems and a correct control policy has improved the quality of the dialysate, minimizing the aluminum exposure. However, an additional problem in Iberoamerica is the difficulty to obtain aluminum-free concentrates for the preparation of the final dialysis solution. Aluminum still seems to be implicated in a great percentage of symptomatic low-bone remodeling lesions in South America compared with Europe, demonstrating that exposure to aluminum through dialysate is still a cause of concern in some areas of the world.

The role of experimental chronic renal failure and aluminium intoxication in cellular immune response.

BACKGROUND: A positive correlation between successful kidney transplantation, few rejection episodes, greater susceptibility to infection and morbidity in patients with high tissue levels of aluminium (Al) indicate that the metal may play a role in the immune response. The aim of this study was to determine if experimental aluminium intoxication could result in significant changes in lymphocyte activity in uraemic and nonuraemic rats. METHODS: Lewis rats were divided into four groups: normals (N), nephrectomized control (U), and Al-treated (N + Al) and nephrectomized Al-treated (U + Al), which received a cumulative dose of 30 mg Al over a 4-week period. Al quantification, histology, histochemical analysis and immunological assays were performed after Al intoxication. RESULTS: High tissue levels of Al and positive histochemical staining in bones were seen in Al-treated rats. Bone histology revealed osteomalacia in U + Al rats. No statistical differences were observed in mixed lymphocyte cultures from controls and Al-treated rats, whereas U and Al-treated rats showed a decrease in lymphoproliferative response to mitogen and natural killer cell cytotoxic activity. A decreased helper T lymphocyte: cytotoxic T lymphocyte cell ratio and a reduction in interleukin-2 production were observed only in the U + Al group. A reduced number of total T lymphocytes was detected in the spleens of all Al-treated rats. CONCLUSIONS: These findings suggest that aluminium toxicity may contribute to immunological impairment in chronic renal failure.

Removal of trace metals by continuous ambulatory peritoneal dialysis after desferrioxamine B chelation therapy.

We studied the removal of aluminum (Al), iron (Fe), copper (Cu), lead (Pb) and zinc (Zn) with continuous ambulatory peritoneal dialysis, before and after desferrioxamine B (DFO) administration (2 g intravenously) in two patients with chronic renal failure and Al-related osteopathy. Both patients had 4 peritoneal dialysis exchanges (2 liters each) per day. Blood concentrations of Al increased 413% (patient A) and 190% (patient B) after DFO. Patient B had a 15% increase in Fe; other metals remained unchanged. Dialysate efflux Al concentrations had peak post-DFO increments of 761% and 840% in patients 1 and 2, respectively. Peak post-DFO increments in Fe dialysate concentration were 342% and 89.5% in the respective patients. Dialysate/plasma (D/P) concentration ratios of Al increased from pre-DFO levels (mean +/- SEM) of 0.370 +/- 0.048 to 0.523 +/- 0.061 after DFO; similarly, Fe D/P ratios increased from 0.259 +/- 0.053 to 0.446 +/- 0.075 with DFO therapy. These results indicate an increase in the ultrafiltrable proportion of Al and Fe in plasma after DFO administration. During 3 days after DFO, patient 1 had a total removal of Al and Fe of 2.9 mg and 4.9 mg, respectively. Metal removal in patient 2 was 7.6 mg of Al and 2.7 mg of Fe. Peritoneal extraction of other trace metals was minor.

Role of aluminum hydroxide in raising serum aluminum levels in children undergoing continuous ambulatory peritoneal dialysis.

Serum aluminum concentrations were measured in 16 children undergoing continuous ambulatory peritoneal dialysis after 7.9 +/- 2.1 (mean +/- SE) and 16.6 +/- 2.3 months of therapy, when the estimated simultaneous oral Al intake from Al hydroxide gels was 98 +/- 20 and 104 +/- 32 mg/kg/day, respectively. Serum Al concentrations were 55.2 +/- 11.4 and 59.8 +/- 10.4 micrograms/L, respectively, compared to 8.2 +/- 1.1 micrograms/L in normal children (P less than 0.001). Serum Al levels correlated with oral Al intake (r = 0.86, P less than 0.001) and inversely with body weight (r = -0.68, P less than 0.01) and age (r = -0.67, P less than 0.01). The youngest patient with the highest serum Al concentrations (208 and 174 micrograms/L) and greatest Al intake (310 and 192 mg/kg/day) had bone biopsy features characteristic of aluminum-related bone disease. Thus, higher aluminum intake per kilogram body weight given to young children is likely to raise the serum Al levels and increase the risk of osteomalacia. Aluminum-containing antacids should be used with caution in infants and young children with renal failure.