Bone Aluminum Research Articles

Aluminum-induced osteogenesis in osteopenic rats with normal renal function.

Previous studies have shown a different effect of aluminum (Al) on bone metabolism in animals with chronic renal failure and conversely, positive osteogenic effects in animals with normal renal function. The aim of this study was to evaluate the effect of aluminum on bone metabolism in osteopenic rats. We studied male Wistar rats with severe osteopenia induced by adding NH4Cl (2%) to the drinking water over a 6-month period. The rats were divided into two groups and followed for 4 months. The Aluminum group (G1) received AlC13 intraperitoneally (10 mg/kg/5 days/week) (n = 8); the Control group (G2) did not receive any treatment after stopping the administration of NH4Cl (n = 5). In all animals we measured biochemical markers (serum Ca, P, Cr, Al, osteocalcin, hydroxyproline) as well as bone mineral density and bone histomorphometry (BV/TV, CTh, ObS/BS, OTh, and NOc/TV). Bone aluminum content, measured by atomic absorption spectrometry, was 101.6 +/- 13 microg/g in the Al overloaded group and 1.31 +/- 0.14 in controls. Bone mineral density, evaluated by dual X-ray absorptiometry (DXA) at the proximal extremity of the tibia was significantly higher in G1 (0.292 +/- 0.01 g/cm2 versus 0. 267 +/- 0.02 g/cm2). No significant differences were found between the biochemical markers. In the histomorphometric parameters we observed significant differences in G1 compared with G2: an increase in BV/TV (18.59 +/- 5.6 versus 7.69 +/- 3.08%) and in CTh (0.52 +/- 0.06 versus 0.36 +/- 0.07 mm) with a moderate increment of the osteoid thickness (14.05 +/- 4.72 versus 5.25 +/- 0.9 microm) (P < 0. 05). Changes in others parameters and the relationship between biochemical parameters of bone remodeling, Al, and histology were analyzed. These findings indicate that in rats with normal renal function, Al is able to induce bone formation even when osteopenia is present.

Longitudinal and lateral variations in the aluminum concentration of selected caprine, bovine, and human bone samples.

Longitudinal and lateral variations in Al concentration in several large animal (bovine and caprine) long bones (tibia and femur) and several human clavicle bones were examined using a sensitive analytical method based on electrothermal atomization atomic absorption spectrometry with Zeeman background correction. Bone segments were carefully removed using special tools free of significant Al contamination, freeze-dried, and digested overnight at room temperature in concentrated HNO3. Bone digestates were analyzed for Al using simple aqueous calibration standards with a Ca(NO3)2 modifier. Mean bone Al concentrations were relatively low (<1 microg/g, dry weight) in bovine and caprine long bones compared to literature values for human bone samples. Longitudinal variations of Al in the animal bones examined appeared relatively uniform compared to the human clavicle bones, where, in three of five cases, Al appeared enriched at the epiphyses (joints). The Al "enrichment" was symmetrical with respect to both left and right clavicle bones. Aluminum concentrations at the mid-shaft of the clavicle bone show less variation compared to whole bone studies, but considerable scatter is evident along the bone length. The mean bone aluminum concentration in the five human subjects varied from 1 to 6 microg/g dry weight.

Bone markers in the diagnosis of low turnover osteodystrophy in haemodialysis patients.

Renal osteodystrophy includes a number of low and high turnover bone histologic patterns which require a bone biopsy for their full identification. The role of intact PTH and several classical and more recent bone markers in the non-invasive diagnosis of renal bone disease in patients with CRF in HD requires further definition since available published data are limited. In addition to intact PTH, alkaline phosphatase (AP) and osteocalcin (BGP), bone alkaline phosphatase isoenzyme (BALP), tartrate resistant acid phosphatase (TRAP), C-terminal cross-linked peptide of collagen type 1 (ICTP) and deoxypyridinoline (DPD) were measured in the serum of 41 patients on haemodialysis, subjected at the same time to transiliac bone biopsy for histomorphometric, histodynamic and aluminium histochemical examination. Histodynamic evaluation following double tetracycline label, was carried out in 37 patients. The patients had no evidence of active cytolytic and cholestatic liver disease and a history of very limited aluminium exposure. The patients had differing degrees of hyper-parathyroidism, with intact PTH ranging from normal to very elevated levels. Serum values of the markers BGP, ICTP and DPD, normally excreted through the kidneys, were on average very high. The correlation coefficients of the humoral parameters vs dynamic variables, such as BFR/BS, were high. The highest values were: intact PTH 0.798, AP 0.900, BALP 0.891, ICTP 0.807. The patients, grouped in low turnover osteodystrophy (LTO; 9), mixed osteodystrophy (MO; 9) and prevalent hyperparathyroidism (HP; 23), showed significant difference in the levels of most humoral and static and dynamic parameters (ANOVA). Bone aluminium histochemistry was negative in all cases. Discrimination of LTO patients from the other groups by humoral parameters, at the highest value of accuracy, showed 100% sensitivity and 93.7% specificity with a cut-off of 12.9 ng/ml for BALP; 88.9% sensitivity and 93.7% specificity with a cut-off of 21.5 ng/ml for DPD, and 88.9% sensitivity and 90.6% specificity with a cut-off of 79.7 pg/ml for intact PTH. The other markers had lower values. A standardized z-score approach for evaluation of all humoral parameters was also carried out. Using all variables, a correct classification of MO/HP and of LTO was possible in 93.8 and 88.9% of the cases, respectively. Predictive power was 96.8 and 80%, respectively for MO/HP and LTO. When the only variables used were intact PTH and BALP, a correct classification of MO/HP and LTO was possible in 90.6% and 88.9%, respectively. Predictive value of MO/HP was 96.7% and for LTO 72.7%. Predictive values using PTH and AP were 96.3% and 57.2%, respectively. Intact PTH and several relatively new bone markers are of certain value in the non-invasive diagnosis of renal osteodystrophy. However some of the humoral markers carry the same quality of information and the use of intact PTH and BALP may be adequate in the discrimination of bone histologic patterns. In cases exempt from liver disease, PTH and AP may be used as a less costly alternative. Bone biopsy could be chiefly limited to cases with borderline humoral values and to all those with a suspected aluminium overload.

An Interesting Case of Osteomalacia Due to Antacid Use Associated With Stainable Bone Aluminum in a Patient With Normal Renal Function

Antacids containing aluminum and magnesium hydroxide are widely used nonprescription agents for treatment of gastritis and peptic ulcer disease. One of the side effects of these antacids is that they bind phosphate in the gut, resulting in its malabsorption. Short-term use, consistent with the directions on the manufacturer’s label, is safe and effective for most patients. Heavy chronic use, even when within label, can cause serious skeletal impairment. This report concerns the case of a 39-year-old pharmacist who self-medicated for peptic ulcer disease with high doses of a potent antacid containing aluminum and magnesium hydroxide. The patient consumed over 18 kg of elemental aluminum and 15 kg of elemental magnesium over 8 years of antacid use. This treatment resulted in the clinical syndrome of severe osteomalacia due to profound phosphate depletion. Bone biopsy revealed stainable aluminum deposits along 27.6% of the total bone surface, which is a unique observation in a patient with normal renal function. Treatment included withdrawing the antacid and supplementation with phosphate, calcium, and vitamin D. She experienced marked subjective and objective improvement with this regimen. This included a striking increase in her bone mineral density occurring over the 2-year follow-up period. This case documents that long-term antacid therapy, even when used by patients with normal renal function and within the manufacturer’s label recommendations, can lead to severe phosphate depletion, osteomalacia, and toxic accumulation of aluminum and magnesium. This clinical syndrome was readily treated by withdrawal of the antacid and with calcium and phosphate supplementation. Physicians recommending treatment with these compounds or learning of their patient’s self-medication with them should inform the patient of the potential serious side effects these agents can cause when used chronically at maximally recommended doses.

Response of young horses in training to varying concentrations of dietary calcium and phosphorus

Summary This experiment was conducted to determine if additional mineral supplementation during early training would increase mineral retention and improve the strength of bone as indicated by the mineral content of the third metacarpal. Twelve previously untrained Quarter Horse geldings were randomly divided into two groups, broke to ride, trained to gallop on the track and maintained in training for four 28-day periods. One group of four horses served as controls and was fed a ration averaging 28.3 g of Ca/day and 21.9 g P/day while in training. Eight other horses were fed a ration averaging 34.9 g Ca/day and 26.4 g P/day while in training. Feed, feces and urine were analyzed to determine mineral balance. Radiographs were taken of the left front leg to examine bone density as indicated by radiographic bone aluminum equivalence (RBAE). The high mineral treatment group retained more Ca than controls (P

Kinetics of aluminum disposition after ingestion of low to moderate pharmacological doses of aluminum.

We assessed the kinetics of aluminum uptake and elimination by tissues of Sprague–Dawley rats following a single gavage dose of 0, 0.25, 0.5, or 1 mmol Al/kg body weight (b.w.) in 1 ml of 16% citrate (equivalent to 0–650 mg Al to a 70-kg human). Serum, liver, kidney, and tibia aluminum concentrations were measured 15, 30, 60, 120, 270, and 360 min after dosing. Serum aluminum concentrations were proportional to dose in rats dosed with 0.25 or 0.5 mmol Al/kg b.w. but were not proportional to dose for rats dosed with 1 mmol Al/kg b.w. Elimination half-lives of serum aluminum were similar for all treatments (102–119 min) which suggests that the non-linear aluminum kinetics in serum reflected a difference in absorption of the highest dose. Although fasted rats dosed with 0.25 or 1 mmol Al/kg b.w. with citrate absorbed aluminum with similar efficiency (4.2% of dose), the length of the absorptive period was prolonged in the rats given the highest does. Total absorbed aluminum mass in rats dosed with 0.25 and 0.5 mmol vs. 1 mmol Al/kg b.w. reached a plateau at 120 vs. 270 min after dosing, respectively. The kinetics of aluminum in liver, bone, and kidney were generally dose-independent. Elimination half-lives of liver aluminum were similar for all aluminum treatments (267–465 min); elimination half-lives could not be estimated in bone and kidney because of turnover exceeded the 6 h collection period.

Relative roles of intestinal absorption and dialysis-fluid-related exposure in the accumulation of aluminium in haemodialysis patients.

A recent retrospective study has clearly demonstrated a reduction of cases with positive bone aluminium (Al) staining in the Italian dialysis population, which in general has had a low prevalence of bone Al toxicity. In the present study we tried to better address the relative role played, in our study population, by enteral and parenteral exposure to Al in reducing bone accumulation. We retrospectively examined the data of 105 DFO tests and bone Al determinations performed in dialysis patients from 1984 to 1995. Enternal exposure was analysed by accurate anamnestic records, while parenteral exposure was evaluated by the determination of Al content in dialysis fluids. Bone Al content was assayed chemically and histochemically, while serum Al was assayed spectrophotometrically. Data pertinent to the patients were allotted into three period groups: 1984-1987; 1988-1991; 1992-1995. As for Al concentrations in dialysis fluids, the interval 1980-1983 (immediately before the start of our study), which could clearly have influenced bone Al content, was also considered. Basal serum Al showed some fluctuations (42.7 +/- 34.1; 24.8 +/- 21.9 and 38.9 +/- 34.9 micrograms/l respectively in the three groups, ANOVA P < 0.01) but only values of the period 1988-1991 were significantly lower than those of the period 1984-1987 (P < 0.05). Increments after DFO did not differ in the three periods (136.5 +/- 105.7; vs 98.7 +/- 91.7 and 106.1 +/- 96.2 micrograms/l respectively, P = n.s.). Enteral exposure to drugs containing Al was comparable (4.1 +/- 2.9 vs 4.0 +/- 4.6 and 5.8 +/- 7.9 total kg ingested respectively; P = n.s.), but bone Al was dramatically reduced (from 60.7 +/- 43.0 to 29.0 +/- 24.4 and 31.9 +/- 29.9 mg/kg/dw respectively; P < 0.0001), along with the definite disappearance of Aluminon-positive cases and Al-related bone disease (ARBD) after 1991. Parenteral exposure through the dialysate dropped from a mean of 26 +/- 14 micrograms/l in the 4-year period prior the start of the study (1980-1983) to 9 +/- 6 micrograms/l in the period 1984-1987 and to 4.9 +/- 2.1 micrograms/l and 5.0 +/- 2.0 micrograms/l respectively thereafter (P < 0.0001). Despite the persistence of oral exposure to Al, responsible for the observed stability of serum Al levels, a definite reduction of bone Al content has been recorded in our dialysis population, and ARBD has disappeared. This result has to be referred essentially to the optimal control of Al content in dialysis fluids, which is confirmed as a major factor for Al intoxication.

Ultrasensitive analysis of the intestinal absorption and compartmentalization of aluminium in uraemic rats: a 26Al tracer study employing accelerator mass spectrometry.

Developments in accelerator mass spectrometry (AMS) now permit the determination of femtogram amounts of 26Al in blood and in various tissues with good precision and free of external contamination. In the present study we used trace quantities of 26Al to investigate the intestinal absorption and compartmentalization of aluminium in rats with renal failure (Nx, 5/6 nephrectomy) and in pair-fed controls (C). Single oral doses of 20 ng 26Al were administered to six animals in each group and, subsequently, 24-h post-load 26Al was analysed in serum, urine, bone, liver, and spleen by means of AMS. Serum concentrations of 26Al were significantly lower in uraemic rats compared to controls, whereas urinary excretion was comparable (Nx, 7.11 +/- 5.78 pg/day vs C, 9.46 +/- 6.10 pg/day), suggesting a higher fraction of ultrafiltrable serum 26Al in uraemia. The target tissues of cellular transferrin-mediated 26Al uptake, liver and spleen, tended to show a larger degree of aluminium accumulation in controls (0.26 +/- 0.31 pg/g vs Nx, 0.14 +/- 0.10 pg/g and 0.37 +/- 0.27 pg/g vs Nx, 0.25 +/- 0.27 pg/g respectively). In contrast, in bone, a site of extracellular aluminium deposition, 26Al concentrations were more elevated in uraemia (1.22 +/- 0.59 pg/g vs C: 0.68 +/- 0.30 pg/g). Estimated total 26Al accumulation in all measured target tissues was significantly higher in uraemic rats (28.15 +/- 9.90 pg vs C: 17.03 +/- 7.03 pg) and total recovery of 26Al from tissue and urine was 26.58 +/- 6.74 pg in controls and 35.75 +/- 7.03 pg in uraemic animals, suggesting a fractional absorption of 0.133% and 0.175% respectively. Our data suggest that fractional absorption from a dietary level dose of 26Al is about 0.13%. Compartmentalization occurs in transferrin-dependent target tissues such as liver and spleen; however, in quantitative terms extracellular deposition in bone is more important. Uraemia has a significant effect on the intestinal absorption and compartmentalization of aluminium. It enhances fractional absorption and increases subsequent extracellular deposition of aluminium in bone. However, at the same time uraemia does not increase transferrin-dependent cellular accumulation of aluminium in liver and spleen.

Biochemical markers for non-invasive diagnosis of hyperparathyroid bone disease and adynamic bone in patients on haemodialysis.

The diagnostic and predictive value of serum intact parathyroid hormone (iPTH) and osteocalcin (bone Gla protein, BGP), alone or in combination, have been examined in only a small number of haemodialysis patients. We studied prospectively 114 patients (46 women, 68 men; mean age 52 +/- 12 years) on regular haemodialysis for a mean of 55 (6-185) months. All patients underwent labelled transiliac bone biopsy, and serum levels of iPTH, BGP and alkaline phosphatase were determined. Seventy-one patients (62%) showed histological findings of hyperparathyroid bone disease, 24 (21%) mixed bone disease, six (5.5%) osteomalacia and 13 (11.5%) adynamic bone. Bone aluminium deposition over more than 25% of the trabecular bone interface was found in 66 patients (58%). Serum iPTH and BGP correlated with the majority of histomorphometric indices of bone formation, mineralization and resorption (r > 0.5, P < 0.01). iPTH levels > or = 200 pg/ml and BGP > or = 50 ng/ml were found to be indicative of hyperparathyroid bone disease, whilst iPTH levels < 65 pg/ml and BGP < 20 ng/ml were indicative of adynamic bone. However, the positive predictive value of these indices was limited (less than 80%), although their negative predictive value, especially when used in combination, was good (more than 90%) and the exclusion of hyperparathyroid bone disease and adynamic bone was possible. The diagnostic and predictive value of these bone markers were improved when patients with bone aluminium deposition were excluded. Diagnosis of hyperparathyroid bone disease and adynamic bone is difficult on the basis of iPTH and BGP, especially when bone aluminium deposition is prevalent. However, using these bone markers, preferably in combination, the exclusion of these lesions is feasible.

Effects of dietary aluminum on chicks Gallus gallus domesticus with different dietary intake of calcium and phosphorus.

Birds that feed in acidified areas may be exposed to an increased intake of aluminum, while their intake of calcium and phosphorus may simultaneously be low. In particular, juvenile birds foraging in acidified areas may suffer from increased effects of aluminum due to high demands of calcium. Day old chicks were fed six different diets where aluminum was combined with normal and low concentrations of dietary calcium and phosphorus for 14 days. The normal calcium-available phosphorus (Ca-P) level was 1.05%-0.45%, and the low dietary Ca-P level was 0.49%-0.21%. Aluminum was given in dietary levels of 0%, 0.13%, and 0.31%. Aluminum had no effects on growth, mortality, or hematocrit, but induced hypocalcemia. Bones accumulated more aluminum than kidneys. A high dietary concentration of aluminum (0.31%) increased the accumulation of aluminum twofold in bones and threefold in kidneys when the dietary concentration of calcium and phosphorus was halved. Opposed to the predictions, bone mineralisation was stimulated by an intermediate increase in dietary aluminum (0.13%) at both levels of dietary calcium and phosphorus. Bone stiffness was also stimulated at this dietary aluminum concentration, but only at the diet low in calcium and phosphorus. A high dietary aluminum concentration did not have any effect on bone stiffness or calcium concentration. Bone stiffness correlated positively with the calcium concentration in bone, and negatively with the aluminum concentration in bone. The effect of dietary aluminum on bone stiffness is probably caused by an alteration in bone mineralization, rather than by the presence of aluminum in bones.

Frequency of adynamic bone disease and aluminium storage in Italian uraemic patients—retrospective analysis of 1429 iliac crest biopsies

Frequency of adynamic bone disease and aluminium storage in Italian uraemic patients—retrospective analysis of 1429 iliac crest biopsies

Lack of an effect of sodium zeolite A on rat tibia histomorphometry

Cell culture studies suggest that the aluminum silicate polymer sodium Zeolite A (SZA) increases bone cell proliferation and extracellular matrix production. This study in rats investigated the short-term (2 weeks) and long-term (18 weeks) in vivo effects of SZA on growth rate (weight gain) and tibia histomorphometry. In separate short-term experiments, female (experiment 1) or male (experiment 2) Sprague-Dawley rats grown and maintained on normal calcium diets were gavaged daily during a 2 week treatment period with 30 mg/kg, 100 mg/kg, or 500 mg of SZA/kg of rat body weight. In the long-term study (experiment 3) ovariectomized (OVX) rats were fed a low calcium diet containing 0, 1.80, and 9.00 g of SZA/kg of diet (0, 125, and 617 mg/kg of body weight, respectively). Short- and long-term treatment of growing rats with SZA resulted in a dose-dependent increase in bone aluminum. In the first experiment, growing intact female rats showed no significant SZA dose-dependent response in growth rate (weight gain) or histomorphometry of cortical bone in the tibial diaphysis or cancellous bone in the secondary spongiosa of the tibial metaphysis. In the second experiment, growing male rats, with right hind limbs immobilized by unilateral sciatic neurotomy, showed no SZA dose-dependent response in growth rate. The longitudinal growth of cancellous bone in the tibia of the denervated limb and the intact contralateral limb were not influenced by sciatic neurectomy and/or by treatment with SZA. Histomorphometry demonstrated that cortical bone mass and formation was reduced in the sciatic-sectioned limb when compared with the contralateral intact limb of vehicle-treated rats, as evidenced by significant reductions in static measurements of cortical bone area (-8.5%) and cross-sectional area (-4.8%) and in calculations of the periosteal formation rate (-33.8%) and mineral apposition rate (-31.6%), and the endocortical formation rate (-35.5%) and mineral apposition rate (-37.9%). The cancellous bone mass of denervated limbs of vehicle-treated rats was also deficient, as evidenced by decreased cancellous bone area (-39.1%) and perimeter (-31.9%). The bone mineral apposition rate was decreased (-26.7%) indicating reduced osteoblast activity. Treatment with SZA did not influence these indices in the tibiae of either sciatic-sectioned limbs or contralateral intact limbs. In the long-term experiment, OVX resulted in a dramatic 88% decrease in cancellous bone volume which was prevented by treatment with 17 beta-estradiol and not influenced by treatment with Zeolite A. The increases in osteoblast and osteoclast number following OVX were not influenced by SZA. The results indicate that SZA treatment has no anabolic effect on cortical and cancellous bone formation and mass in normal growing female rats and that this compound does not protect against osteopenia due to reduced load bearing in the growing male rat or gonadal hormone deficiency in adult female rats.

Rapid and reliable method for the determination of aluminium in bone by electrothermal atomic absorption spectrometry

A reliable method for the determination of aluminium in bone by electrothermal atomic absorption spectrometry (ETAAS) is described. Bone samples were digested in concentrated HNO3 using a closed-vessel microwave digestion system. Accurate and precise results were obtained by calibration against aqueous Al standards prepared in solutions containing 1% v/v HNO3 and 1.0 g l-1 Ca, as Ca(NO3)2, as modifier. No modifier was needed for the bone digestate. A method detection limit (3 sigma) of 0.023 microgram g-1 for bone was obtained. The between-day precision for bone digestate was about 7% at a mean concentration of 10 micrograms l-1. The method was validated against the NIST standard reference materials SRM 1486 Bone Meal and SRM 1577b Bovine Liver. To help confirm the concept of the Al in bone method, essentially the same method, with some minor modifications, was used for the determination of Al in serum and dialysis fluid. The method performance was monitored by participation in two international interlaboratory comparison programmes for serum and dialysis fluid Al available from Canada (CHUL, Québec) and the UK (Robens Institute). The performance over a 10 month period was excellent for both serum and dialysis fluid proficiency test samples distributed by these programmes.

Use of the low-dose desferrioxamine test to diagnose and differentiate between patients with aluminium-related bone disease, increased risk for aluminium toxicity, or aluminium overload

Aiming at a safe method in the diagnosis of aluminium-related bone disease (ARBD)/aluminium overload the low-dose desferrioxamine (DFO) test was developed. In a multicentre study histological and histochemical data and aluminium bulk analysis of bone biopsies of 77 dialysis patients were correlated with the results of both the 5 mg/kg and 10 mg/kg DFO tests. ARBD was considered to be present when > 15% of the bone surface was positively stained for aluminium and the bone formation rate was below 220 microns 2/mm2/day. Patients in which the Aluminon staining was positive (> 0%) were considered at an increased risk for aluminium toxicity independent of the type of renal osteodystrophy. Patients were considered aluminium overloaded when the bone aluminium content was > 15 micrograms/g wet weight and/or the Aluminon staining was positive (> 0%). Using the proposed criteria 15 patients were found to have ARBD; 13 of them presenting with a serum iPTH below 150 ng/l. In conjunction with an iPTH measurement the DFO test had a more than acceptable sensitivity and specificity in the diagnosis of ARBD. The test was considered positive when a post-DFO serum aluminium increment (delta sA1) above 50 micrograms/l (5 mg/kg) or 70 micrograms/l (10 mg/kg) together with a serum iPTH below 150 ng/l was found. Using these cut-off levels the 5 and 10 mg/kg tests in the diagnosis of ARBD had a sensitivity of 87% and a specificity of 95% and 92% respectively whereas the predictive value for a positive test for the population under study was 80% (5 mg/kg). Not a single patient with a serum iPTH > 650 ng/l had a positive staining (> 0%) even when the bone aluminium level was elevated (> 15 micrograms/g wet weight). In the detection of patients at risk for aluminium toxicity delta sA1 thresholds of 50 micrograms/l (5 mg/kg) and 70 micrograms/l (10 mg/kg) in combination with a serum iPTH < 650 ng/l had a sensitivity of 92% and specificity of 86% and 84% respectively. In the clinical setting of aluminium overload, threshold delta sA1 levels of 50 micrograms/l (5 mg/kg) and 70 micrograms/l (10 mg/kg) had a sensitivity of 91% and a specificity of 95% and 90% respectively. The low-dose DFO test is a reliable test for the detection of aluminium overload; however, it is not specific enough to differentiate between ARBD, increased risk of aluminium toxicity, and aluminium overload unless it is used in combination with a serum iPTH measurement. In conjunction with a serum iPTH measurement it is an important tool in the differential diagnosis and may avoid the necessity of a bone biopsy in the majority of patients. Data obtained in the present study have allowed us to update the strategies for monitoring, diagnosis and patient follow-up proposed at the Consensus Conference on Diagnosis and Treatment of Aluminium Overload in End-Stage Renal Failure; Paris, 1992.

Bone disease in predialysis, hemodialysis, and CAPD patients: Evidence of a better bone response to PTH

The spectrum of bone disease in predialysis and dialysis patients has changed during the last decade. The incidence of aplastic bone disease has increased and this can not be attributed to bone aluminum deposition; moreover, low bone cellular activity is present despite a moderate elevation in PTH levels. This study compares PTH levels and types of bone disease in both predialysis and dialysis patients from the same geographical area. We prospectively studied 119 unselected end-stage renal disease patients: 38 were immediately predialysis (PreD), 49 on hemodialysis (HD), and 32 on CAPD. A bone biopsy was performed in all patients. Aplastic bone disease with < 5% bone surface aluminum was a common finding (48%, 32%, and 48%, in PreD, HD, and CAPD, respectively). In all groups, an intact PTH level below 120 pg/ml was highly predictive of low bone turnover. Conversely, a PTH level above 450 pg/ml was always associated with histologic features of hyperparathyroid bone disease. Among the bone histomorphometric parameters, osteoblast surface showed the best correlation with intact PTH in each group, and the slope of the regression line for this correlation was significantly steeper in HD and CAPD than PreD patients. Thus, the range of PTH (95% confidence limit bands) needed to obtain a normal osteoblast surface of 1.5% was greater in preD than in HD and CAPD patients (300 to 500 vs. 75 to 260 pg/ml, respectively). In all groups some degree of marrow fibrosis was observed when PTH levels were greater than 250 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone aluminium content in Alzheimer's disease.

The possible association between aluminium and Alzheimer's disease is still contentious. If aluminium neurotoxicity is implicated in the pathophysiology of Alzheimer's disease, it may result either from excessive aluminium exposure or increased brain aluminium uptake. In a pilot study to test the former hypothesis, trabecular bone aluminium content, which reflects long-term aluminium exposure, was evaluated in 7 patients with a clinical diagnosis of senile dementia of the Alzheimer type (SDAT; mean age 80.8 +/- 3.35 years) and 19 non-demented age-matched controls (mean age 79.6 +/- 6.09 years). Trabecular bone was obtained from post-traumatic femoral neck fracture specimens taken from patients during femoral head prosthesis surgery. Bone aluminium content was expressed quantitatively by atomic absorption spectrometry and qualitatively by the acid solochrome azurine histological staining technique. Quantitative analysis showed a lower aluminium content in the SDAT (11.9 +/- 4.04 micrograms/g dry bone) versus the non-demented group (18.2 +/- 7.37 micrograms/g), which was significant at the 95% but not at the 99% confidence limit. Aluminium deposition from qualitative histological analysis was not detectable in either group. These results do not support a hypothesis of excessive aluminium absorption and tissue accumulation in Alzheimer's disease.

Aluminum retention by aged rats fed aluminum and treated with desferrioxamine

Our primary purpose was to assess the impact of chronic exposure to dietary aluminum on aging rats. Male rats were fed diets containing 0.4 or 36.8 μmol Al/g diet for 8 months until 23 months of age. The aging rats fed supplemental aluminum accumulated more aluminum in sera, tibias, and kidneys than control rats, but accumulated similar concentrations of aluminum in bone as young rats fed aluminum for short periods of time in previous studies. Although the rats had increased bone turnover (as indicated by urinary hydroxyproline excretion) after 22 months of age, the amount of bone turnover was not sufficient to explain the urinary excretion of aluminum by the aged rats.

Electrothermal atomic absorption spectrometric determination of Al, Cu, Fe, Pb, V and Zn in clinical samples and in certified environmental reference materials

This work presents the electrothermal atomic absorption spectrometric (ETAAS) determination of aluminum (Al), copper (Cu), iron (Fe), lead (Pb), vanadium (V) and zinc (Zn) in whole blood, blood components, bone and urine specimens from hemodialyzed azotemic patients and healthy subjects, and in certified environmental reference materials. Prior to the ETAAS analysis, test portions of the samples were diluted at different ratios in appropriate solvents: (i) whole blood, blood plasma, blood serum and red blood cells, in 0.1% v/v Triton X-100; (ii) urine, in 0.1% v/v Triton X-100 + 0.01 mol l −1 nitric acid; and (iii) mineralized samples (e.g., bone, pond sediment, vehicle exhaust particulates and sargasso), in 0.01 mol l −1 nitric acid. For Al, Cu, Fe and Zn, the diluent solutions also acted as the analyte isoformation solutions. For Pb and V, the analyte isoformation solutions were 0.5 mg l −1 of palladium + 2% m/v of citric acid and 0.1 mg l −1 of palladium + 2% m/v of citric acid in 0.01 mol l −1 nitric acid-0.1% v/v Triton X-100, for the former and for the latter, respectively. These analytical isoformers were not combined directly with the specimens in order to eliminate any precipitate formation, particularly with whole blood and its components. The detection limits (3σ, μg l −1), were 0.5 (Al), 0.3 (Cu), 0.5 (Fe), 0.1 (Pb), 0.4 (V) and 0.1 (Zn). Accuracy was evaluated by using whole blood, human serum, freeze-dried urine, pond sediment, vehicle exhaust particulates and sargasso reference materials. For all metals present in real samples, precision was better than 3.0% R.S.D. The proposed methods were used to establish the metal concentrations found in the clinical samples under consideration. The methods were free from interferences, reliable and reproducible.

Aluminum concentrations in tissues of rats: effect of soft drink packaging

Aluminum is a commonly occurring trace element for which no nutritional requirements have been set. Some non-conclusive evidence exists suggesting a need of aluminum for growth, reproduction or health of man and animals. There is concern that exposure or consumption of aluminum may be toxic to humans and animals. The objective of the current study was to compare tissue levels of aluminum of rats fed soft drinks packaged in aluminum cans, glass bottles or distilled water. Thirty male weanling rats (Sprague-Dawley) were divided into three treatment groups of 10 rats each. All rats were fed rodent chow ad libitum throughout the study. Three different fluids, i.e. distilled water, diet soft drinks from aluminum cans and diet soft drinks from glass bottles, were fed for a period of 3 weeks. Aluminum contents of tissues were measured by atomic absorption spectrophotometry. Canned soft drink fed rats had significantly higher blood, liver and bone aluminum concentration than rats that were given glass bottled soft drink. There was a 69% higher bone aluminum concentration and 16% lower femur weight in rats fed aluminum canned soft drinks when compared with rats fed with distilled water.

Adynamic bone disease with negative aluminium staining in predialysis patients: prevalence and evolution after maintenance dialysis.

Aplastic bone disease (ABD) is a common form of renal osteodystrophy and is characterized by a defect in bone matrix formation and mineralization without an increase in osteoid thickness. The prevalence and pathogenesis of ABD in predialysis patients is largely unknown. We prospectively studied 92 unselected predialysis patients with a creatinine clearance < 10 ml/min/1.73 m2 and a mean age of 45 +/- 2 years (61 M, 31 F). None of the study patients had received any form of vitamin D therapy, and CaCO3 was the primary phosphate binder. Aplastic bone disease was observed in 30 (32%) patients. Stainable bone aluminium surface was < 3% in all ABD patients. Patients with ABD were older (52 +/- 3 versus 42 +/- 2 years; P < 0.01) and had reduced serum intact PTH compared to non-ABD patients (199 +/- 25 versus 561 +/- 87 pg/ml; P < 0.001). Patients with diabetes mellitus showed lower PTH values (179 +/- 31 versus 432 +/- 62 pg/ml; P < 0.001) and a lower incidence of advanced hyperparathyroidism bone lesions (16% versus 46%; P < 0.05) than non-diabetic patients. However, diabetes was not clearly associated with low bone turnover disease (56% in diabetics versus 41% in non-diabetics; P = 0.1). A second bone biopsy was obtained in eleven ABD patients after a period of 16.6 +/- 2.2 months on maintenance dialysis with a dialysate calcium of 7 mg/dl. Bone histology was unchanged in 10 patients, and one evolved to mild hyperparathyroidism. Trabecular bone volume did not change (22.7 +/- 1.7 versus 20.7 +/- 1.7%), and the stainable bone aluminium surface remained < 3%.(ABSTRACT TRUNCATED AT 250 WORDS)