Note: This article was originally published with an incorrect version of the Acknowledgments, which appeared on p. 218 of the print version. The correct version of the Acknowledgments appeared on pp. 1–2. The corrected article is available below.

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Human Health Risk Assessment for Aluminium, Aluminium Oxide, and Aluminium Hydroxide

Background. Adynamic bone disease was recently described to be increasingly prevalent in the dialysis population. At present the diagnosis of this type of renal osteodystrophy can only be made by bone histomorphometry. We assessed the value of different biochemical serum markers in the diagnosis of adynamic bone disease. Methods. In 103 haemodialysis patients a bone biopsy was performed after double tetracycline labelling, and the serum levels of intact PTH, osteocalcin, and the bone isoenzyme of alkaline phosphatase were determined. Bone alkaline phosphatase was measured by an optimized agarose gel electrophoretic method, recently shown to have a high accuracy, precision and reproducibility, also in the lower range. Results. In 38 (37%) of the patients the diagnosis of adynamic bone disease was histologically established. Constructing receiver operator curves optimal cut-off levels for the diagnosis of adynamic bone disease were determined, being ≤27 U/litre for the bone isoenzyme of alkaline phosphatase, ≤14 μg/litre for osteocalcin and ≤150 pg/ml for intact PTH. Concentrations of bone alkaline phosphatase or intact PTH below these cut-off levels, were shown to be the best performing tests in the detection of adynamic bone disease as indicated by a sensitivity of 78.1 and 80.6% and a specificity of 86.4 and 76.2% respectively. Applying Bayes' theorema, it was calculated that in the current haemodialysis population in which a prevalence of adynamic bone disease up to 35% has been described, the positive predictive values for the proposed cut-off values are 75% for bone alkaline phosphatase, 65% for intact PTH and 55% for osteocalcin. Moreover, in this population, levels of bone alkaline phosphatase and intact PTH below the optimal cut-off excluded hyperparathyroid bone disease. Conclusion. In view of the relative easy and accurate methodology for bone alkaline phosphatase determination, the closer physiological link with osteoblast function and the lesser expense for its determination we suggest that this marker is a useful tool in the noninvasive diagnosis of the adynamic type of bone disease in the individual patient.

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Low serum levels of alkaline phosphatase of bone origin: a good marker of adynamic bone disease in haemodialysis patients

Human exposure to toxic metals: factors influencing interpretation of biomonitoring results.

Background: Little is known about trace metal alterations in the bones of dialysis patients or whether particular types of renal osteodystrophy are associated with either increased or decreased skeletal concentrations of trace elements. Because these patients are at risk for alterations of trace elements as well as for morbidity from skeletal disorders, we measured trace elements in bone of patients with end-stage renal disease.

Methods: We analyzed bone biopsies of 100 end-stage renal failure patients enrolled in a hemodialysis program. The trace metal contents of bone biopsies with histological features of either osteomalacia, adynamic bone disease, mixed lesion, normal histology, or hyperparathyroidism were compared with each other and with the trace metal contents of bone of subjects with normal renal function. Trace metals were measured by atomic absorption spectrometry.

Results: The concentrations of aluminum, chromium, and cadmium were increased in bone of end-stage renal failure patients. Comparing the trace metal/calcium ratio, significantly higher values were found for the bone chromium/calcium, aluminum/calcium, zinc/calcium, magnesium/calcium, and strontium/calcium ratios. Among types of renal osteodystrophy, increased bone aluminum, lead, and strontium concentrations and strontium/calcium and aluminum/calcium ratios were found in dialysis patients with osteomalacia vs the other types of renal osteodystrophy considered as one group. Moreover, the concentrations of several trace elements in bone were significantly correlated with each other. Bone aluminum was correlated with the time on dialysis, whereas bone iron, aluminum, magnesium, and strontium tended to be associated with patient age. Bone trace metal concentrations did not depend on vitamin D intake nor on the patients’ gender.

Conclusions: The concentration of several trace elements in bone of end-stage renal failure patients is disturbed, and some of the trace metals under study might share pathways of absorption, distribution, and accumulation. The clinical significance of the increased/decreased concentrations of several trace elements other than aluminum in bone of dialysis patients deserves further investigation.

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Aluminum, Iron, Lead, Cadmium, Copper, Zinc, Chromium, Magnesium, Strontium, and Calcium Content in Bone of End-Stage Renal Failure Patients

Atomic Absorption, Atomic Emission, and Flame Emission Spectrometry

Direct measurement of lead and cadmium in blood and urine by electrothermal atomic absorption spectrometry with deuterium background correction (D2-AAS) is prone to severe matrix and spectral interferences. We overcame these effects by coating the L'vov platform with ammonium molybdate, reducing the atomization time, introducing a post-atomization cooling step, carefully selecting ashing and atomization temperatures, and using an appropriate procedure for matrix modification. To determine Pb and Cd in blood and urine, we used matrix-matched calibration curves. With the proposed procedure for sample preparation, both Pb and Cd in whole blood can be determined in the same diluted sample. Results obtained by D2-AAS correlate closely with those by Zeeman-corrected AAS. Detection limits (mean blank + 3 SDblank) for Pb in urine and blood were 4 micrograms/L. For cadmium, the detection limits were 0.4 and 0.1 micrograms/L for urine and blood analysis, respectively. Between-run CVs were less than 5.0%.

Elimination of matrix and spectral interferences in the measurement of lead and cadmium in urine and blood by electrothermal atomic absorption spectrometry with deuterium background correction

A method was developed for the determination of gadolinium (Gd) in biological material using graphite furnace atomic absorption spectrometry (GFAAS). The element is first extracted into methyl isobutyl ketone and then reextracted into hydrochloric acid. Factors influencing the recovery of extraction such as pH, choice of chelating agents, and hydrochloric acid concentration have been investigated. The element is determined under STPF (stabilized temperature platform furnace) conditions with atomization from a tantalum boat. Under optimized furnace conditions, the use of the tantalum boat improved sensitivity substantially compared to the use of pyrolytically coated graphite tubes. Around 150 measurements could be performed with 1 boat. Memory effects, being a common problem in the GFAAS determination of lanthanoids, were no longer observed after insertion of the boat. The characteristic mass and detection limit (2SD; SD = standard deviation) of the Gd determination are 1000 and 2060 pg, respectively. The precision evaluated as the relative standard deviation (RSD) of six analyses was below 10% for tissue Gd concentrations ranging from 0.92 to 72.0 micrograms g-1. The recovery of added analyte ranged between 92.0% and 99.3%. The method was found to be suitable for studying the pharmacokinetics and biodistribution of Gd in rats.

Determination of gadolinium in biological materials using graphite furnace atomic absorption spectrometry with a tantalum boat after solvent extraction.

A simple, rapid and low-cost method for the routine determination of iron in urine and serum using graphite furnace atomic absorption spectrometry is described which may provide an alternative to the more widespread automated spectrophotometric methods. The urine and serum samples were simply diluted with water prior to analysis. Matrix modification was found to be redundant. The standard additions technique or the use of matrix matched standards (addition calibration) was found to be unnecessary and, therefore, the calibration was performed using aqueous standards. For serum analysis the degree of dilution could be reduced by using the less sensitive 302.0-nm resonance line, yielding more precise determinations, and for urine analysis, interferences were eliminated by means of a L'vov platform. The interferences that exist in the presence of nitric acid are also discussed. Finally, the presence of background absorption was investigated by means of Zeeman effect atomic absorption.

Direct determination of iron in urine and serum using graphite furnace atomic absorption spectrometry

We describe a direct-calibration method for determining aluminum in bone and soft tissues by graphite furnace atomic absorption spectrometry. Aluminum in bone was determined in uncoated tubes, whereas the analytical performance in soft tissue analysis was markedly improved by using pyrolytically coated tubes with a L'vov platform and added calcium. The analytical imprecision (CV) was less than or equal to 5.4% for aluminium concentrations between 12 and 98 micrograms/L, and analytical recoveries of added analyte varied between 94.5% and 103.0%. Detection limits (2 SD of determinations of the zero standard) were 7 and 6 pg for bone and soft tissues, respectively. Characteristic masses (amounts of Al yielding an absorbance signal of 0.0044 A) were 9 and 8 pg, respectively.

Lian Liang

Papers

Elimination of matrix and spectral interferences in the measurement of lead and cadmium in urine and blood by electrothermal atomic absorption spectrometry with deuterium background correction

Determination of gadolinium in biological materials using graphite furnace atomic absorption spectrometry with a tantalum boat after solvent extraction.

Direct determination of iron in urine and serum using graphite furnace atomic absorption spectrometry

Direct calibration for determining aluminum in bone and soft tissues by graphite furnace atomic absorption spectrometry.