Bone Aluminum Research Articles

Measurement of Equine Bone Mineral Content by Radiographic Absorptiometry Using CR and Ortho Systems

The purpose of this investigation was to establish the accuracy and precision of bone mineral content (BMC) measurements made by the total radiographic bone aluminum equivalence (RBAE) method in the evaluation of the horse skeleton. To study the accuracies and precisions of the total RBAE method, the analogue ortho system and the digital computed radiography (CR) system were used. For investigation of the correlation with the bone ash weight and total RBAE value, the clinically healthy left third metacarpal bone (McIII) of 30 post-mortem horses were used. In the evaluation of the accuracies and precisions of total RBAE method, three different values were measured using an aluminum stepwedge. A high positive correlation was noted between the bone ash weight of the measured region and the total RBAE value. The precisions of the total RBAE method were high when measurements with a low total RBAE value by the ortho system and a high total RBAE value by the CR system were excluded, use of the development-fixing solution was limited to within 3 days in the ortho system. The RBAE value changed when the X-ray irradiation angle was altered in the horizontal and vertical directions in both systems, thus an accurate dorsopalmar view is demanded. Based on these findings, the total RBAE method of McIII in horses using the ortho and CR systems had high precision, suggesting it is a reliable tool for the measurement of BMC in horses.

Improvement of adynamic bone disease after renal transplantation

Low bone remodeling and relatively low serum parathyroid hormone (PTH) levels characterize adynamic bone disease (ABD). The impact of renal transplantation (RT) on the course of ABD is unknown. We studied prospectively 13 patients with biopsy-proven ABD after RT. Bone histomorphometry and bone mineral density (BMD) measurements were performed in the 1st and 12th months after RT. Serum PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and osteocalcin were measured regularly throughout the study. Serum PTH levels were slightly elevated at transplantation, normalized at the end of the third month and remained stable thereafter. Bone biopsies performed in the first month after RT revealed low bone turnover in all patients, with positive bone aluminum staining in 5. In the 12th month, second biopsies were performed on 12 patients. Bone histomorphometric dynamic parameters improved in 9 and were completely normalized in 6, whereas no bone mineralization was detected in 3 of these 12 patients. At 12 months post-RT, no bone aluminum was detected in any patient. We also found a decrease in lumbar BMD and an increase in femoral BMD. Patients suffering from ABD, even those with a reduction in PTH levels, may present partial or complete recovery of bone turnover after successful renal transplantation. However, it is not possible to positively identify the mechanisms responsible for the improvement. Identifying these mechanisms should lead to a better understanding of the physiopathology of ABD and to the development of more effective treatments.

Release of elements from retrieved maxillofacial plates and screws

Vitallium appliances and surrounding tissues were investigated to evaluate the release and accumulation of elements. Four microplates, sixteen screws and surrounding tissues were removed from three patients presenting inflammation 4 to 6 years after surgery and were submitted to SEM and X-ray microprobe analysis. Histology was performed on paraffin or PMMA sections of tissues.A continuous release of elements from metallic appliances into soft tissues was observed. Cobalt, chromium, and nickel were detected in soft and boney tissues in close proximity to the appliance. Aluminium, as a component of screw coatings, accumulated in soft tissues, and a remarkable amount of aluminium was detected in the dense lamella of lamellar bone. The results suggest that coatings containing aluminium should be avoided and the time these appliances are allowed to remain in patients should be shortened. Further studies on element release and the fate of aluminium in bone are warranted.

The aluminum content of bone increases with age, but is not higher in hip fracture cases with and without dementia compared to controls

Aluminum is considered a potentially toxic metal, and aluminum poisoning may lead to three types of disorders: aluminum-induced bone disease, microcytic anemia and encephalopathy. This is well known in patients with chronic renal failure, but since healthy subjects with normal renal function retain 4% of the aluminum consumed, they are also at risk of long-term low-grade aluminum intoxication. Included in this study were a total of 172 patients (age range 16-98 years) with the aim of examining whether aluminum accumulates in bone with increasing age. Additionally, we aimed to investigate whether the aluminum content of bone differs between controls and hip fracture cases with and without dementia, in particular in those with Alzheimer's disease. During operations for all cases, bone biopsies were taken with an aluminum-free instrument from the trabecular bone. The samples were measured for their content of aluminum using an inductively coupled mass spectrometer. We found an exponential increase in aluminum content of bone with age. The average aluminum values, adjusted for age, were similar in men and women (P=0.46). No significant differences in sex- and age-adjusted mean aluminum values between the controls and the hip fracture cases with (P=0.72) and without (P=0.33) dementia could be detected. The average aluminum concentration among cases with Alzheimer's disease was also similar to the values of hip fracture patients with other types of dementia (P=0.47). Odds ratios of hip fracture for each quartile of aluminum content in bone were also estimated to detect non-linear effects, but we did not find any statistically significant association remaining after age and sex adjustment. Thus, our results indicate that we accumulate aluminum in bone over our life span, but this does not seem to be of major pathogenetic significance for the occurrence of hip fracture or dementia.

In vivo measurement of bone aluminium: Recent developments

A biomarker of aluminium accumulation in the human body can play a valuable role in determining health effects of chronic aluminium exposure, complementing other human and environmental monitoring data. In vivo neutron activation provides such a non-invasive biomarker. To date, the best in vivo neutron activation system used thermalised neutrons from a nuclear reactor at Brookhaven National Laboratory, which suffered only slightly from interference from other elements, primarily phosphorus, and from the disadvantage of restricted accessibility. At McMaster, we use a nuclear reaction on an accelerator to select neutron energy, which eliminates the interferences. Spectral decomposition analysis improved sensitivity. A new 4π detection system also enhanced sensitivity. Together these improvements yield a minimum detection limit of 0.24 mgAl in a hand, slightly better than at Brookhaven and equivalent to “normal” levels. Further improvements should result from a new irradiation cavity and from using a higher proton current on the accelerator to shorten irradiation times. The system is now ready for pilot human studies.

Short-duration exercise and confinement alters bone mineral content and shape in weanling horses

The hypothesis that short-duration exercise may ameliorate the decrease in bone mass observed with confinement was investigated with 18 quarter horses (nine colts and nine fillies) weaned at 4 mo of age and placed into box stalls. After a 5-wk adjustment period, individuals were grouped by age and weight, and then divided randomly into three treatment groups: 1) group housed; 2) confined with no exercise; and 3) confined with exercise. The confined and exercised groups were housed in 3.7 m x 3.7 m box stalls for the 56-d duration of the trial. The exercised group was sprinted 82 m/d, 5 d/wk, in a fenced grass alleyway. The weanlings were led down an alleyway, turned loose in a small pen, and then released and allowed to run back down the alley. The group horses were housed together in a 992-m2 drylot with free access to exercise. On d 0, 28, and 56, dorsopalmar and lateromedial radiographs of the left third metacarpal bone were taken to estimate changes in bone mineral content and cortical widths. Mean values of medial, lateral, and total radiographic bone aluminum equivalence increased over time (P < 0.05), whereas dorsal and palmar radiographic bone aluminum equivalence did not change significantly. Dorsal, medial, and total radiographic bone aluminum equivalence tended (P = 0.09) to differ by a treatment x day interaction, with values increasing over time only in the exercised group. Normalized medial and total radiographic bone aluminum equivalence tended (P < 0.1) to differ (P < 0.01) with treatment, with exercised horses having greater bone aluminum equivalence than confined horses. Dorsopalmar cortical width in exercised horses was greater than on d 56 (treatment x day; P = 0.07). The dorsopalmar medullary cavity decreased in exercised vs. group-housed horses (P = 0.027), whereas dorsal and medial cortical width tended to increase only in the exercised horses (treatment x day; P < 0.01). This study indicated that a short-duration exercise protocol might be effective in improving bone mass and therefore skeletal strength in horses.

Effects of Exercise on Bone Metabolism in Yearling Horses

Sixteen yearling Quarter Horses were used in a split-plot-designed experiment to determine the effects of exercise on bone metabolism. Horses were blocked by sex and BW and then randomly assigned to either the exercised (EX) or non-exercised (NEX) treatment. Diets were formulated to meet or exceed NRC requirements for yearlings in moderate growth. Diets were fed at 2.5% of BW and consisted of a pelleted concentrate, prairie grass hay, and alfalfa cubes in a 50:30:20 ratio, respectively. Radiographs of the third metacarpal (MCIII) were taken on d 0, 45, and 90 for determination of radiographic bone aluminum equivalence (RBAE). Blood was taken every 14 d throughout the trial to measure carboxy-terminal propeptide of type I procollagen (PICP) and carboxy-terminal telopeptide of type I collagen (ICTP) concentrations in serum. Although no differences between treatments were found in RBAE within days measured, a significant decrease in RBAE was observed between d 0 and 90 for the NEX horses. This decrease in bone optical density throughout the duration of the trial indicates that stalling and lack of exercise may result in a greater loss of bone mineral content (BMC) as compared with horses that were forced to exercise. Consequently, the EX horses may be better prepared for future mechanical stresses placed upon them.

Accumulation of aluminium in lamellar bone after implantation of titanium plates, Ti–6Al–4V screws, hydroxyapatite granules

Titanium plates, Ti6Al4V screws and surrounding tissues, and biopsies of hydroxyapatite (Osprovit ®) grafts of maxillary sinus lifting were investigated to evaluate the release and accumulation of ions. Optical microscopy, SEM and X-ray microanalysis were carried out to evaluate the plates and screws removed from patients presenting inflammation and biopsies. Ions release from metallic appliances or leaching from granules towards soft tissues was observed. An accumulation of aluminium but not titanium was found in soft tissues. A peculiar accumulation of aluminium in the dense lamella of newly formed bone was recorded. The results seem to indicate that biological perturbations may be related to aluminium release from the tested biomaterials. The aluminium content of these biomaterials, its diffusion and accumulation are discussed. Further studies on ion release from biomaterials and aluminium fate in skeletal tissues are suggested.

Prospective Evaluation of an In-Center Daily Hemodialysis Program

Short duration daily hemodialysis (DHD) emerges as a well-tolerated alternative to standard hemodialysis (SHD). In this prospective study 5 patients in SHD were recruited to participate in an in-center DHD program. The SHD consisted of 3 sessions of 4 h each per week. Nonproportional mixture machines without an ultrafiltration control device and low flow dialyzers were used. For DHD, dialysis equipment and procedures were kept the same. Dialysis sessions, however, began at 6 p.m. (from Monday to Saturday) and lasted 2 h. Data from the last 6 months on SHD of the same patients were compared with the ones from each semester on DHD. Bone biopsy was performed at start and at the end of the 2-year study period. Hypotensive episodes, hypertensive crisis, cramps and headaches became 7–10 times less frequent in daily dialysis. A significant fractional increase (∼12%) was seen in mean values for hematocrit. Predialysis urea levels as well as predialysis creatinine levels declined significantly. Also lower during the daily dialysis period were the mean values for both phosphorus and Ca×P product. Significant increases were found in serum bicarbonate, albumin and in dry weight. The frequency of mean blood pressure ≧110 mm Hg on arrival for dialysis was significantly lower in every semester on daily hemodialysis. A significant twofold improvement in quality of life scoring was observed. Finally, daily hemodialysis also seemed to be beneficial to low turnover bone disease and bone aluminum deposition. These beneficial effects occurred despite of an increase in the frequency of missing days. Results from the present study which prospectively addressed the role of in-center short daily hemodialysis in the management of ESRD are encouraging.

Renal Osteodystrophy in Predialysis and Hemodialysis Patients: Comparison of Histologic Patterns and Diagnostic Predictivity of Intact PTH

Background: Comparison of renal osteodystrophy in predialysis and hemodialysis has been rarely reported. Distinct patterns of renal osteodystrophy could be found in these conditions. In addition the use of parathyroid hormone (PTH) and other markers for noninvasive diagnosis may result in different predictive values in predialysis and hemodialysis patients. Methods: 79 consecutive patients with conservative chronic renal failure and 107 patients on hemodialysis were studied. All patients were subjected to bone biopsy for histological and histomorphometric evaluation. The patients had no exposure to aluminium before dialysis and relatively low exposure while on hemodialysis. Results: In the predialysis patients, bone biopsies showed 9 cases of adynamic bone disease (ABD) and 8 cases of osteomalacia (OM), 50 patients with mixed osteodystrophy and 2 cases of hyperparathyroidism. Among the hemodialysis patients 12 cases had ABD, 3 cases OM, 30 mixed osteodystrophy, and 61 patients hyperparathyroidism. In the predialysis patients with chronic renal failure, bone aluminium was on average 4.5 mg/kg dry weight, while in dialysis patients the average value was 35.4 mg/kg dry weight. Discriminant analysis of low turnover osteodystrophy (ABD and OM) by intact PTH showed higher accuracy in dialysis than in predialysis patients. Correlation studies of intact PTH versus bone formation rate, osteoblast surface/bone surface and osteoclast surface/bone surface showed significantly steeper slopes in dialysis than in predialysis patients, which indicates that bone resistance to PTH is more marked in predialysis patients. Conclusions: The prevalence of ABD and OM in the geographic area investigated is lower than in other reports. Aluminium exposure does not seem to be the cause of low turnover osteodystrophy in the present population. The predictive value of intact PTH in the noninvasive diagnosis of renal bone disease is higher in hemodialysis patients than in predialysis patients. Predialysis chronic renal failure, when compared to the dialysis stage, seems to be characterized by resistance of bone tissue to PTH.

The clinical impact of aluminium overload in renal failure.

Chronic aluminium exposure and toxicity related to aluminium absorption and contaminated dialysis fluid continue to be a problem for many patients with renal failure, particularly in South America and in some developing countries. The two most prevalent sources of aluminium in this population are water used to prepare dialysate and aluminium-containing phosphate binders. Of particular concern is the effect of aluminium at the level of the bone, the haematopoietic system and the brain. Here we focus mainly on the adverse effects of aluminium on bone, the preferred organ of aluminium accumulation in the body. Unfortunately, aluminium has a cumulative effect, thus even short-term exposure to aluminium in phosphate binders adds to the total load and may contribute to the risk of aluminium-related bone disease. Even a bone biopsy does not allow a precise determination of total bone aluminium content. We examine the mechanisms by which aluminium contributes to abnormal bone remodelling. Studies indicate that aluminium has a direct effect, inhibiting bone formation and resorption. There is also evidence for an indirect effect through the action of aluminium on parathyroid hormone synthesis and by its modulation of calcium activity. We discuss commonly used techniques for identifying aluminium load and review studies of chelation therapy as a method to lower aluminium load. It is apparent that aluminium overload has serious consequences for patients with chronic renal failure, yet this problem can be largely prevented by the use of aluminium-free phosphate binders. The deleterious effects on bone remodelling caused by chronic exposure to aluminium suggest that caution should be observed when using other metals as phosphate binders.

The effect of calcium and phosphorus supplementation on bone metabolism in young, mature, and aged horses during inactivity and subsequent aerobic training

An experiment was performed to determine the effects of Ca and P supplementation, inactivity, and subsequent aerobic exercise on bone metabolism in young, mature, and aged horses. Twelve stock-type geldings were blocked into three groups: 2 and 3, 7 to 11, and 15 to 21 years of age. Horses within age groups were evenly divided and randomly assigned to one of two dietary treatments; control (C) or Ca and P supplementation (T). Horses consuming C and T received about 133% and 275% of National Research Council (NRC) requirements for Ca and P, respectively. The trial consisted of eight 21-day periods. During periods I, II, and III, all horses were inactive and received no forced exercise. During periods IV, V, VI, VII, and VIII, all horses were placed on an ascending aerobic exercise regimen. Blood samples were taken at the beginning of period I and at 21-day intervals thereafter to determine serum concentrations of osteocalcin (OST) and type I carboxyterminal telopeptide (ICTP). Dorsal-palmar and lateral-medial radiographs were taken of the left third metacarpal at the beginning of period I and at 21-day intervals thereafter to monitor changes in bone densities, as indicated by radiographic bone aluminum equivalencies (RBAE). Mean serum OST was affected by age (P < .004) and the interaction of time and age (P < .006). Mean serum ICTP was affected by age (P < .001), time (P < .001), the interaction of time and age (P < .001); and the interaction of time and treatment (P < .05). There was an effect of treatment on overall mean medial (MRBAE; P < .04) and total (TRBAE; P < .04) RBAE. Overall mean dorsal RBAE (DRBAE; P < .001), palmar RBAE (PRBAE; P < .003), lateral RBAE (LRBAE; P < .001), MRBAE (P < .001), normalized MRBAE (P < .001), TRBAE (P < .05), and normalized TRBAE (P < .05) were affected by time. There was an effect of the interaction of time and age on overall mean DRBAE (P < .05), LRBAE (P < .002), MRBAE (P < .02), normalized MRBAE (P < .02), TRBAE (P < .005), and normalized TRBAE (P < .005). Overall mean DRBAE (P < .02) and PRBAE (P < .001) were affected by the interaction of time, treatment, and age. Biochemical and radiographic data from this experiment indicate that dietary Ca and P supplementation may affect bone remodeling in aerobically exercised horses of varying ages following a period of inactivity. Furthermore, the data indicate that bone in horses of varying ages responds differently to inactivity and exercise.

Effects of in-center daily hemodialysis upon mineral metabolism and bone disease in end-stage renal disease patients

Alternative hemodialysis schedules have been proposed to improve the quality of the dialysis. Nonetheless, their influence upon mineral and bone disorders is unknown. To report the impact of a daily hemodialysis schedule upon the lesions of renal osteodystrophy. Prospective non-controlled study. Public University Hospital. Five patients treated by daily hemodialysis for at least 24 months. Daily dialysis sessions were accomplished with non-proportional dialysis machines without an ultrafiltration control device, with blood flow of 300 ml/min, bicarbonate dialysate ([Ca]=3.5 mEq/L) at 500 ml/min, and low-flux membrane dialyzers. Sessions were started at 6:00 p.m. (except Sundays) and lasted 2 hours. Serum levels of Ca and P from the last 6 months on conventional hemodialysis for the same patients were used for comparison with each semester of daily hemodialysis. Bone biopsies and PTH levels were obtained at the end of the conventional hemodialysis period and then again after 2 years of daily hemodialysis. Mean serum calcium was significantly higher during the second and third semesters of daily dialysis [10.0 mg% (SD 0.6), and 10.0 mg% (SD 0.8), respectively] compared to standard dialysis [9.4 mg% (SD 0.8)], p < 0.05. Mean values for phosphorus were significantly lower during every semester of daily hemodialysis [6.3 mg% (SD 1.8), 5.8 mg% (SD 1.7), 6.0 mg% (SD 1.7), and 6.0 mg% (SD 1.8)] compared to standard dialysis [7.2 mg% (SD 2.7)], P < 0.05. Variations in mean Ca x P product followed the same pattern as for phosphorus [59.5 (SD 16.0), 57.1 (SD 16.3), 59.8 (SD 17.7), and 58.31 (SD 20.9) vs. 68.6 (SD 27.3), P < 0.05]. After 2 years on daily hemodialysis, 2 patients who had aplastic lesion were found to have mild bone disorder. In addition, one patient with mixed bone lesion and moderate bone aluminum accumulation had osteitis fibrosa with no aluminum. Intact PTH values at the beginning of study and after 2 years on daily hemodialysis did not differ [134 pg/ml (SD 66) vs. 109 pg/ml (SD 26), P = 0.60, respectively]. Patients treated using daily hemodialysis had better control of serum phosphorus and perhaps a lower risk of metastatic calcifications. Daily hemodialysis also seemed to be beneficial to low turnover bone disease and bone aluminum deposition.

Bone aluminum uptake in uremic rats receiving intraperitoneal iron.

To assess the effect of concomitant iron and aluminum loads on bone aluminum accumulation and on the response to the deferoxamine test in rats with the same aluminum surcharge, Wistar rats with chronic renal failure were divided into three groups: iron-overloaded rats (N = 6) (intraperitoneal iron); iron-depleted rats (N = 6) (blood withdrawal two to three times per week); control rats (N = 4) (no manipulation). All groups received intraperitoneal aluminum simultaneously. After 6 wk, a deferoxamine challenge test was performed. Thereafter, bone aluminum and iron were measured. The iron-overloaded rats showed higher bone iron content (iron overloaded: 147.7+/-55.4 microg/g; iron depleted: 7.9+/-1.0, and controls 13.3+/-9.9 microg/g, p < 0.010) and lower bone aluminum content (iron overloaded: 14.2+/-4.0 microg/g; iron depleted: 70.9+/-35.1 microg/g; controls: 72.7+/-28.3 microg/g p < 0.005). No differences were found between the iron-depleted and control rats. After the deferoxamine infusion, the iron-depleted rats tended to have higher serum aluminum increments (p = NS) and higher urinary aluminum excretion (p < 0.012, p < 0.020) than control rats despite similar amounts of aluminum in bone of the two groups. Aluminum bone accumulation was minor if iron and aluminum loads were given concomitantly. The iron depletion influenced the results of the deferoxamine challenge test in rats with similar bone aluminum burden.

Bone density in the juvenile racehorse treated with exogenous somatotropin (eST)

Thirty juvenile horses were paired by age within sex, and one horse from each pair was randomly assigned to either eST treatment or to a control group. The horses were “broke” to ride and trained in a regimen typical for young racehorses. Radiographs were taken on days 0, 32, 50, 64, 82, 96 and 128 of the study. Increase in total radiographic bone aluminum equivalence (RBAE) was significantly greater in eST treated horses than in the control group (P<.003). Increase in medial RBAE was also significantly greater due to eST treatment (P<.0001). Trends were apparent for increases due to eST treatment in dorsal RBAE (P=.07) and lateral RBAE (P=.07). Bone density was selectively increased in the dorsal, lateral and medial vs. the palmar cortex in the eST treated horses.

Monte Carlo design study for in vivo bone aluminum measurement using a low energy accelerator beam

The need for aluminum monitoring exists in occupational medicine, as well as for the clinical monitoring of patients with renal dysfunction. After the development of an appropriate neutron source card, Monte Carlo simulations were made to design moderator/reflector assembly consisting of a polyethylene moderator (2 cm) and graphite reflector (30 cm), surrounded by a boronated (5%) wax (20 cm) and lead (1 cm) shield. This design should allow for the bone aluminum measurement of healthy subjects, but prior to that detailed microdosimetry is necessary to address a noticed disagreement between theoretical and experimental dose data.

Ionogran in revision arthroplasty.

Glass ionomer cement (Ionocem) was developed for use in bone surgery and is reported to be notably biocompatible. Between 1991 and 1994 we performed revision operations for aseptic loosening of arthroplasties of the hip on 45 patients using this material in its granulate form (Ionogran) mixed with homologous bone as a bone substitute. Of these 45 patients, 42 were followed up for a mean of 42 months. Early reloosening of the acetabular component has occurred in ten after a mean of 30 months. Histological examination showed large deposits of aluminium in the adjacent connective tissue and bone. Osteoblastic function and bone mineralisation were clearly inhibited. The serum levels of aluminium were also increased. The toxic damage at the bone interface caused by high local levels of aluminium must be seen as an important factor in the high rate of early reloosening. Our findings cast doubt on the biocompatibility of this material and we do not recommend continuation of its further use in orthopaedic surgery.

Increased bone strontium levels in hemodialysis patients with osteomalacia

In this study, we report on the association between increased bone strontium levels and the presence of osteomalacia in end-stage renal failure patients treated by hemodialysis. We performed a histologic examination and determined the strontium content and strontium/calcium ratios in bone biopsies of 100 hemodialysis patients recruited from various centers all over the world. Aside from the bone strontium concentration, the bone aluminum content was assessed. The bone zinc concentration, a nonrelevant element for bone toxicity, was also measured. Bone strontium levels and bone strontium/calcium ratios were increased in subjects with osteomalacia when compared with those with the other types of renal osteodystrophy. Bone strontium and bone calcium levels correlated with each other. The slope of the linear regression curve correlating these parameters was much steeper in the osteomalacic group (Y = 2.22X - 120) as compared with the other types of renal osteodystrophy (Y = 0.52X - 5.7). Within the group of patients with osteomalacia, bone strontium levels also significantly correlated with the bone aluminum content (r = 0.72, P = 0.018). No such correlation was found for the other types of renal osteodystrophy. The bone zinc concentration of subjects with normal renal function did not differ significantly from the values noted for the various types of renal osteodystrophy taken as separate groups, nor could increased bone zinc concentrations be associated with a particular bone lesion. Our data demonstrate an association between osteomalacia and increased bone strontium concentrations in dialysis patients. Further studies are warranted to establish whether strontium plays either a primary, secondary, or contributive role in the development of the latter type of renal osteodystrophy.

Screening plasma aluminum levels in relation to aluminum bone disease among asymptomatic dialysis patients.

Aluminum accumulation in plasma and tissues is a well-described complication among persons undergoing peritoneal dialysis or hemodialysis. Excess bone aluminum is associated with low bone formation rates and increased risk for fractures. Current recommendations for care of patients with end-stage renal disease include screening for aluminum toxicity with plasma aluminum levels; patients with levels below 40 microg/L are considered to be at low risk for aluminum bone disease (ABD). We examined data from the Toronto Renal Osteodystrophy Study to evaluate the performance of plasma aluminum levels in screening for ABD. Two hundred fifty-eight unselected patients undergoing peritoneal dialysis (n = 143) or hemodialysis (n = 115) underwent diagnostic bone biopsy and measurement of plasma aluminum level. Sixty-nine patients (26.7%) were identified as having ABD, defined as low or normal bone formation rates with 25% or more bone surface aluminum staining. Plasma aluminum level was strongly associated with the presence of ABD; the odds ratio was 1.4 for each increase of 10 microg/L (95%CI, 1.2, 1.6). However, only 50.1% of patients with a plasma aluminum level of 40 microg/L or greater had ABD, whereas 14.2% of patients with a level below this threshold also had ABD. Using this cutoff level of 40 microg/L, the sensitivity and specificity were 65.2% and 76.7%, respectively. We conclude that although there is a correlation between high aluminum levels and ABD, a patient's plasma aluminum level does not predict well the presence of ABD in spite of a relatively high prevalence of disease.

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

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. 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. 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. 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.