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NDT Advance Access originally published online on April 4, 2006
Nephrology Dialysis Transplantation 2006 21(8):2217-2224; doi:10.1093/ndt/gfl146
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Original Articles: Dialysis and Transplantation

Evolution of bone and plasma concentration of lanthanum in dialysis patients before, during 1 year of treatment with lanthanum carbonate and after 2 years of follow-up

Goce B. Spasovski1, Aleksandar Sikole1, Saso Gelev1, Jelka Masin-Spasovska1, Tony Freemont2, Isabel Webster3, Maggie Gill3, Chris Jones3, Marc E. De Broe4 and Patrick C. D'Haese4

1 Department of Nephrology, University of Skopje, Macedonia, 2 Department of Osteoarticular Pathology, The Medical School, University of Manchester, UK, 3 Shire Pharmaceuticals Group plc, Basingstoke, UK and 4 Department of Physiopathology, Facutlty of Medicine, University of Antwerp, Belgium

Correspondence and offprint requests to: Goce B. Spasovski, MD, PhD, Department of Nephrology, University Clinical Center, Vodnjanska 17, 1000 Skopje, Macedonia. Email: gspas{at}sonet.com.mk



   Abstract
Top
 Abstract
Introduction
 Methods
 Laboratory methods
 Results
 Discussion
 Conclusion
 References
 
Background. Lanthanum carbonate (LC) has been proposed as a new phosphate binder. Presented here are the results from one centre that participated in a multicentre trial to assess the effect of treatment with LC and calcium carbonate (CC) on the evolution of renal osteodystrophy in dialysis patients. Bone biopsies were performed at baseline, after 1 year of treatment and after a further 2-year follow-up period to assess the lanthanum concentration in bone and plasma.

Methods. Twenty new dialysis patients were randomized to receive LC (median dose 1250 mg) for 1 year (n = 10), followed by 2 years of CC treatment or CC (n = 10) during the whole study period (3 years).

Results. After 36 weeks of treatment, steady state was reached with plasma lanthanum levels varying around 0.6 ng/ml. Six weeks after cessation of 1 year of treatment, the plasma lanthanum levels declined to a value of 0.17 ± 0.12 ng/ml (P < 0.05) and after 2 years to 0.09 ± 0.03 ng/ml. Plasma and bone lanthanum levels did not correlate with the average lanthanum dose at any time point. The mean bone concentration in patients receiving LC increased from 0.05 ± 0.03 to 2.3 ± 1.6 µg/g (P < 0.05) after 1 year and slightly decreased at the end of the study to 1.9 ± 1.6 µg/g (P < 0.05).

Conclusions. Bone deposition after 1 year of treatment with LC is low (highest concentration: 5.5 µg/g). There is a slow release of lanthanum from its bone deposits 2 years after the discontinuation of the treatment and no association with aluminium-like bone toxicity.

Keywords: bone biopsy; calcium carbonate; lanthanum carbonate; renal failure; renal osteodystrophy



   Introduction
Top
 Abstract
 Introduction
Methods
 Laboratory methods
 Results
 Discussion
 Conclusion
 References
 
In patients with chronic renal failure (CRF), abnormalities in bone histology known as renal osteodystrophy (ROD) are already observed before dialysis treatment is started [1,2]. The decline in renal function in end-stage renal disease (ESRD), leads to high serum phosphorus levels, which stimulate parathyroid hormone (PTH) secretion [3]. Additionally, insufficient calcitriol production in patients with ESRD and/or insufficient calcium intake [4] may increase PTH secretion and thus can contribute to the development of high-turnover ROD indirectly. Hence, to achieve an adequate control of hyperphosphataemia, patients are administered phosphate binders, of which aluminium hydroxide and calcium carbonate (CC) have historically been the most widely used. Although very effective, aluminium containing compounds accumulate in the body and can lead to the development of low-turnover bone diseases (osteomalacia or adynamic bone), encephalopathy and/or microcytic anaemia [5,6]. Calcium-based binders, particularly when used in combination with vitamin D analogues, may result in over-suppression of PTH and development of adynamic bone disease. In particular, a high intake of dietary calcium in the form of phosphate binders has been linked to increased levels of coronary calcification [7]. Both a high and low bone turnover have been associated with the development of vascular calcifications, which are strongly associated with cardiovascular disease, a major cause of mortality and morbidity [7–9].

Clearly, there is a need for alternative phosphate binders that are not associated with these side effects during phosphate control. Sevelamer hydrochloride (RenaGel®) is a non-calcium, non-aluminium, synthetic phosphate binder that has been shown to reduce serum phosphorus concentration in patients with ESRD [10]. Moreover, there are indications that the treatment with sevelamer hydrochloride slows the progression of cardiovascular calcification and also reduces the rate of hypercalcaemia compared with calcium-based therapies [11]. However, the high doses required to effectively control phosphorus levels may affect patient compliance and cause gastrointestinal side effects [11,12]. Studies suggest that treatment with sevelamer hydrochloride results in reduced bicarbonate levels [13,14] and may affect the absorption of fat-soluble vitamins [15]. In addition, the effect of this treatment on histomorphometric indices of bone turn-over has not yet been reported.

Lanthanum carbonate (LC) is a non-aluminium and non-calcium based phosphate binder. Clinical studies have indicated that the compound is well-tolerated and effectively reduces serum phosphorus levels [16,17]. Moreover, the results of a large multicentre trial by D’Haese et al. [18] showed that treatment with LC for 1 year resulted in a tendency towards normalization of bone histomorphometric parameters with no evolution towards low-turnover bone or aluminium-like bone disease. Animal studies examining lanthanum's bio-distribution in brain and cerebrospinal fluids after intravenous administration of the maximum tolerated intravenous dose of lanthanum chloride (1 mg/kg/day) indicated very low concentrations herein [19]. Recently, Lacour et al. [20], after oral dosing of LC, reported an increased tissue lanthanum content in rats with CRF as compared with animals with normal renal function, suggesting that the uraemic state might enhance intestinal absorption of the drug. At present, the knowledge on the accumulation/elimination of lanthanum in serum and bone of uraemic patients is still highly limited and a better insight would be of particular importance for a safe use of the drug.

The aim of this bone biopsy-based single-centre study was: (i) to evaluate plasma and bone lanthanum levels during 1 year of LC treatment and after a 2-year of follow-up period during which the lanthanum treatment was replaced by CC and (ii) to investigate whether bone lanthanum deposition is associated with aluminium-like bone toxicity.



   Methods
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 Abstract
 Introduction
 Methods
Laboratory methods
 Results
 Discussion
 Conclusion
 References
 
Patient selection
Patients who had started dialysis within 12 weeks prior to study entry, or were scheduled to begin dialysis before randomization, were screened. Twenty six adult, new dialysis patients, who had required oral phosphate binders to control serum phosphorus levels, were recruited. The number of patients taking concomitant erythropoietin, iron supplementation and vitamin D during the 1-year study was well balanced between and within the groups. Patients with any significant gastrointestinal problem, a history of treatment with corticosteroids or bisphosphonates, or presenting with hypocalcaemia at screening were excluded from the study. All of the patients who completed the initial 1-year study were asked to take part in the follow-up assessment.

A total of 24 patients were randomized to receive at least one dose of LC (n = 12) or CC (n = 12). From this group, 20 patients completed the 1-year study and underwent a bone biopsy at baseline and after 1-year of treatment. Two LC-treated patients were excluded due to protocol violation, one CC-treated patient died in the last month of the study, whilst the biopsy specimen of a second CC-treated patient taken at the end of the study was not suitable for histomorphometric analysis. After a 2-year follow-up period, during which patients received treatment with CC, a third bone biopsy was performed in 19 patients (LC, n = 9; CC, n = 10).

The mean (±SD) age of patients (±SD) was 55 ± 10 years in the LC-group and 57 ± 10 years in the CC-group; in both groups 60% of the population was male. The primary cause of renal failure included hypertension (30%), interstitial kidney disease (25%), polycystic kidney disease (20%), diabetes (20%) and glomerulonephritis (5%); there was no important difference between the treatment groups with respect to the primary cause of ESRD.

The Ethical Committee of the Medical Faculty of the University of Skopje (Macedonia) approved the protocol for the study investigating the effect of 1 year of treatment with LC or CC on bone in patients with ESRD. Following completion of this investigation, a protocol amendment was submitted to the Committee and permission was granted for the collection of a third bone biopsy at the end of the 2-year follow-up period. Written informed consent was obtained from all the recruited patients, and the study was conducted in compliance with the standards for Good Clinical Practice and the Declaration of Helsinki [21].

Study design
The treatment phase of the study was conducted over a 1-year period. After screening, double tetracycline labelling was administered, with an interval of 8–12 days [22]. Phosphate binding treatment was stopped at the time of labelling. Baseline transiliac bone biopsy was then performed 2–6 days after the second label and patients were randomized to receive either LC or CC treatment. Patients attended fortnightly visits for the first 8 weeks of the study and thereafter monthly, in order for the study medication dosage to be titrated for each patient as required. The LC was titrated up to a maximum dose of 3000 mg/day elemental lanthanum, and CC to a maximum dose of 4000 mg/day in order to achieve optimal control of serum phosphorus levels (≤1.8 mmol/l).

After 1 year of treatment with either phosphate binder, a second bone biopsy was performed following the same procedure as described earlier. Patients were assessed and any adverse events were recorded during 1 year of treatment and at 4 weeks after the discontinuation of the study medication. The use of erythropoietin, vitamin D and calcium was monitored closely throughout the study.

During the next 2 years patients were maintained on standard CC therapy, according to routine clinical and laboratory practice. A third bone biopsy was performed at the end of this period following the standard procedure described earlier.



   Laboratory methods
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 Abstract
 Introduction
 Methods
 Laboratory methods
Results
 Discussion
 Conclusion
 References
 
Blood and bone biochemistry
Blood samples were taken at every study visit for routine biochemistry and haematology tests. In addition, a panel of serum markers relevant to bone (e.g. bone-specific and total alkaline phosphatase, intact PTH (iPTH), 25-(OH)D3, and 1,25-(OH)2D3) and liver function (alanine aminotransferase, gamma glutamyl transpeptidase) were measured at regular time intervals, according to standard methodologies, using appropriate assay kits.

Bone biopsy cores of ~1 cm in length were obtained using a Bordier–Meunier needle with an internal diameter of 5 mm. The bone was divided into two parts. A first small part, consisting of mainly cortical bone, was used for measurement of the total lanthanum content. A second larger part of mainly trabecular bone was fixed in absolute ethanol and embedded in methylmethacrylate. Slices of undecalcified bone were stained with toluidine blue [23]. The tetracycline labels were evaluated by fluorescence microscopy on 7 µm unstained sections mounted in immersion oil. Histological classification of ROD was performed according to the criteria previously described in detail [18,24].

Lanthanum was regularly measured in plasma every 12 weeks during the lanthanum treatment and at 2 years after cessation of the treatment. Lanthanum in bone (wet weight) was determined at baseline, after a 1-year study period and after 2 years of follow-up in both patient groups. Lanthanum concentration in plasma and bone was measured by means of inductively-coupled plasma mass spectrometry (ICP-MS) using methodologies developed and optimized at the Center for Analytical Sciences (CAS) at the University of Sheffield, UK. The detection limit for the determination of plasma lanthanum levels with this method during 1 year of treatment and at the 2-year follow-up was 0.03 and 0.05 ng/ml, respectively, while in bone it was set at 0.02 µg/g.

Statistical analyses
Comparison between the two groups of the various serum parameters studied was performed by means of Student's t-test. The percentage of patients belonging to categorical variables (sex, diabetes) was compared by {chi}2 analysis. The association between different parameters was assessed by Pearson correlation coefficient. A P-value <0.05 was considered to be significant at a two-tailed level. Results are expressed as mean ± SD for serum (bio-)chemistry, and mean ± SD, median and range for bone lanthanum content, unless otherwise stated. Statistical analysis was performed using SPSS 10.0 for Windows statistical software.



   Results
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 Abstract
 Introduction
 Methods
 Laboratory methods
 Results
Discussion
 Conclusion
 References
 
Haematology and biochemistry
At baseline there were no significant differences in biochemical parameters between the two treatment groups. At the end of the first year of treatment, no significant difference in serum levels of calcium, phosphorous, bone-specific and total alkaline phosphatase, iPTH, 25-(OH)D3, 1,25-(OH)2D3, and liver enzymes compared with baseline levels was reported in either treatment group (Table 1). However, a comparison of mean serum calcium levels for the first year of treatment showed that the level was significantly higher in the CC group compared with the LC group (2.36 ± 0.28 vs 2.13 ± 0.19 mmol/l; P = 0.02).


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  		Table 1. Biochemical and bone histomorphometry data of the various groups at baseline, 1- and 3-year study period (data expressed as mean ± SD)

 
Safety and efficacy
Serum phosphorus levels did not show any statistically significant differences over time or between groups (Table 1). A mean serum phosphorus level ≤1.8 mmol/l was achieved in nine patients from each treatment group during the 1-year trial period. The median dose of elemental lanthanum used was 1250 mg (range: 750–3000 mg); the therapeutical dose was recorded at regular time intervals and the average daily dose was calculated for each patient (Table 2). Treatment was well tolerated when taken with meals and no serious adverse events or withdrawals were reported. The median dose of CC used was 2000 mg (range: 1000–4000 mg). During the study period, a significantly (P < 0.05) higher incidence of hypercalcaemia (serum calcium above upper limit of normal, i.e. >2.6 mmol/l) was reported in CC-treated patients (50%) compared with those receiving LC (0%).


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  		Table 2. Bone and plasma lanthanum levels and average lanthanum oral doses over 1 year of treatment (data expressed as mean ± SD)

 
Lanthanum levels in plasma and bone
Baseline plasma lanthanum levels were below 0.03 ng/ml in most of the patients of both groups. During LC treatment, lanthanum levels increased reaching a maximal level of 1.26 ± 1.24 ng/ml (range: 0.07–3.29 ng/ml) at 24 weeks, after which they stabilized at a value varying around 0.60 ng/ml (Figure 1). Compared with the values noted at cessation of lanthanum treatment, a significant decline of plasma lanthanum levels was noted at 6 weeks of follow-up (0.59 ± 0.52 vs 0.17 ± 0.12 ng/ml; P < 0.05). There was no further significant decrease in mean plasma lanthanum concentration during the further 2 years of follow-up (0.09 ± 0.03 ng/ml). At this time point, plasma lanthanum levels in patients of the LC group remained significantly higher compared with those of patients of the CC group (<0.05 ng/ml) (Table 1). Plasma lanthanum levels did not correlate with the average lanthanum dose at any time point (Table 3), nor with the serum creatinine values at 12 or 24 weeks of the study.


Figure 1
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  		Fig. 1. Evolution of the plasma lanthanum levels of patients receiving LC (grey bars) and CC (black bars) treatment for 52 weeks, at week 58 and after 2 years of treatment with CC. Data are expressed as mean±SE.

 

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  		Table 3. Correlation matrix of bone and plasma lanthanum levels and average lanthanum oral doses after 1 year of treatment with LC and 2 years of follow-up

 
The mean bone lanthanum concentration at baseline was similar in both groups (0.048 ± 0.02 µg/g in LC vs 0.044 ± 0.02 µg/g in CC group). The concentration of lanthanum in bone increased in all patients during the trial (Figure 2). The mean bone concentration in patients receiving LC for 1 year was significantly higher 2.3 ± 1.6 µg/g (median 2.5 µg/g; range 0.5–5.5 µg/g) as compared with 0.1 ± 0.04 µg/g (median 0.1 µg/g; range 0.05–0.16 µg/g) in the CC group (P < 0.05). The mean bone lanthanum concentration in the LC group at the end of the follow-up period had slightly decreased to 1.9 ± 1.6 µg/g (median 1.4 µg/g; range: 0.5–5.6 µg/g) compared with the 1-year bone lanthanum levels (P < 0.05) (Figure 2). The mean bone lanthanum concentration in the CC group gradually increased from 0.1 ± 0.04 µg/g (median 0.11 µg/g; range: 0.05–0.16 µg/g) at the 1-year biopsy to 0.15 ± 0.06 µg/g (median 0.15 µg/g; range: 0.07–0.27 µg/g) at the end of the follow-up period (Figure 2, open circles). There was no correlation between the bone lanthanum content and the average lanthanum dose at any time point (Table 3), nor with the mean serum creatinine for the first year study.


Figure 2
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  		Fig. 2. Bone lanthanum concentrations of patients receiving LC (solid circles) and CC treatment (open circles) for 12 months, followed by 2 years of treatment with calcium carbonate. Each line represents an individual patient. Note that 2 years after completion of the study, bone lanthanum concentrations in two patients who received LC treatment further increased by ≥10%. In one patient, bone lanthanum levels remained unchanged (<10% difference) whilst they had decreased in six patients (>20% lower).

 
The bone lanthanum content in biopsies from the LC group collected at the end of the 1-year study significantly correlated with plasma lanthanum at the 1- and 2-year follow-up (R = 0.93; R = 0.80, respectively; P < 0.01) while the bone lanthanum content in biopsies taken after 2 years of follow-up correlated significantly with plasma lanthanum levels at 1 year (R = 0.95; P < 0.01) (Table 3).

At the 1-year biopsy, none of the patients in the LC group developed low bone turnover, in contrast to the CC group in which three patients had developed a dynamic bone. The moderate increase in the number of osteoblasts from 14.45 ± 7.92% at baseline up to 21.23 ± 15.88% (P = 0.19) after 1 year of LC treatment, remaining unchanged after 2 years of follow-up (20.27 ± 15.70%), further supports the hypothesis that bone lanthanum deposition is not associated with aluminium-like bone toxicity (Table 1). A similar pattern was observed for the bone formation rate (BFR). However, there was no difference between the groups for osteoid volume (OV) and mineral apposition rate (MAR) data (Table 1).



   Discussion
Top
 Abstract
 Introduction
 Methods
 Laboratory methods
 Results
 Discussion
Conclusion
 References
 
Due to the impaired renal function, mineral metabolism is disturbed in patients with CRF, particularly those treated by dialysis. This may result in hyperphosphataemia, hyperparathyroidism and an increased risk of vascular calcifications. Hence, in these patients an adequate control of phosphate is required. Past and currently used phosphate binders such as aluminium hydroxide or CC, however, may promote the development of severe side effects [5–9].

In the search for a safe and efficient alternative, LC has recently been introduced. Being an efficient phosphate binder, some concern has been raised as to whether the therapeutic use of the compound may result in deposition and/or toxic side effects of the element, since, from a physicochemical point of view, lanthanum shows some similarities with aluminium.

In the present study, we investigated the evolution of the plasma and bone lanthanum concentration during 1 year of treatment with LC and a 2-year follow-up period after cessation of treatment during which patients received CC. This is a rather small study as a result of which some of the data have to be interpreted cautiously and deserve further confirmation.

At baseline, i.e. before treatment, only minute amounts (~0.03 ng/ml) of lanthanum were found in plasma. During treatment, a rapid increase in plasma lanthanum levels was observed reaching a plateau at around 0.6 ng/ml. This relatively low concentration is in accordance with the reported low gastrointestinal absorption of the element in humans (0.00089%) [25], i.e. 2–3 orders lower than that reported for aluminium (0.02–0.14%) [26,27] for which plasma levels up to 100 ng/ml or more have frequently been observed in the past. These not only resulted from the element's higher gastrointestinal absorption compared with lanthanum, but are also due to the fact that aluminium, in contrast to lanthanum, is mainly excreted via the kidney, posing an increased risk for accumulation of the element in dialysis patients, in contrast to lanthanum that is mainly excreted via the bile. Moreover aluminium may also accumulate in the body by the use of aluminium-contaminated dialysis fluids, a risk that is quasi non-existent for lanthanum.

The lanthanum plasma concentration declined rapidly within a few weeks after cessation of treatment, but remained detectable even 2 years after cessation of treatment. This suggests a first rapid non-renal elimination phase followed by a slow release from, most likely, the bone compartment. Lanthanum accumulation in the liver was not assessed and could not be ruled out. However, the absence of any liver damage was indirectly evidenced by the absence of any increase in the mean level of the liver enzymes in either group, at any time point.

Bone samples taken at baseline in both groups contained low amounts of lanthanum (<0.05 µg/g). After 1 year of treatment with LC, bone lanthanum levels had increased up to 2.3 ± 1.6 µg/g, the maximum concentration being 5.5 µg/g. There was only a slight decrease in the bone lanthanum concentrations during the follow-up period, indicating a slow release into the plasma compartment. This slow release is also reflected by the higher plasma lanthanum levels in these patients as compared to those of the CC group after 2 years of follow-up. We found a significant correlation between bone and plasma lanthanum levels in LC-treated patients at various time points. While the bone concentration at any point in time will depend on the duration of lanthanum treatment (time component), bone is exposed to lanthanum entirely via the plasma and therefore the plasma concentration should determine the rate of deposition in bone (concentration component). A relationship between plasma and bone lanthanum concentrations therefore might be expected. It should be noted, however, that based on the data of the present study, measurement of plasma lanthanum levels may not be considered a reliable routine method for assessing the lanthanum body burden or the bone lanthanum content in the general dialysis population.

The highest concentration ever observed in the bone of dialysis patients was 10 µg/g (70 nmol/g) wet weight after 4 years of treatment with LC (Shire Pharmaceuticals Ltd, data on file). Considering a bone calcium concentration of 120 mg/g (3 mmol/g) and assuming a rather heterogeneous distribution of lanthanum throughout the bone [28] (quiescently and actively mineralizing surface, deeper parts of mineralized bone), the molar bone lanthanum/calcium ratio would be as low as 2 x 10–5, i.e. only one out of 50 000 calcium atoms would be replaced by lanthanum. Applying the same reasoning to aluminium [29] and assuming the total amount of the element (up to 50 µg/g, 1.8 µmol/g) to be localized in only 1% of the total bone volume, which is a reasonable assumption in patients with aluminium-related osteomalacia in which the element is localized mainly at the mineralization front, the molar bone aluminium/calcium ratio would be 6 x 10–2. In other words, one out of 16 calcium atoms would be replaced by aluminium, increasing the probability of toxic effects at the level of apatite nucleation, crystal growth and structure.

Interestingly, neither plasma nor bone lanthanum levels correlated with the average oral lanthanum dose (900–2500 mg/day) at any time point. The patient presenting the highest bone lanthanum concentration even had received the lowest dose and vice versa. This indicates that the gastrointestinal absorption is variable from one patient to another. Absolute concentrations were extremely low for all patients. Variable absorption is typically seen for drugs that have a very low oral bioavailability and therefore, was not unexpected. Furthermore, as the pharmacokinetics of lanthanum are non-linear (sub-proportional), a correlation between dose and plasma levels (and hence bone levels) would not be expected. According to the recent study by Lacour et al. [20], the condition of CRF imparts a unique pre-disposition towards higher accumulation and/or retention of lanthanum in tissues, which they suggest is at least partially explained by an increase in intestinal lanthanum absorption. Data from the experimental studies [30] support the hypothesis that the uraemic state may lead to higher gastrointestinal absorption as reflected by the higher liver lanthanum concentration in CRF vs sham-operated rats after oral loading. There was no difference between the intravenously loaded CRF and sham-operated rats. On the other hand, clinical studies have shown that plasma lanthanum exposure and pharmacokinetics are similar in dialysis patients and healthy subjects, suggesting that exposure of systemic tissues to lanthanum is not enhanced in ESRD [31]. This hypothesis is also supported by the findings of the present study showing no correlation between serum creatinine and plasma lanthanum levels (or bone lanthanum levels after 1 year).

The bone histomorphometric data of patients in the LC group revealed lanthanum deposition not to be accompanied by any aluminium-like effects on bone, hereby confirming previously reported data [18,32]. Indeed, at the 1-year biopsy, none of the patients in the LC group developed low bone turnover; this in contrast to the CC group in which three patients had developed adynamic bone. The moderate increase in the number of osteoblasts after 1 year of LC treatment, remaining unchanged after 2 years of follow-up, despite almost unchanged bone lanthanum levels, further supports the hypothesis that bone lanthanum deposition is not associated with aluminium-like bone toxicity. A more or less similar pattern was observed for the BFR. In contrast, the number of osteoblasts in the CC group at 1 year was slightly decreased and moderately increased after the 2-year follow-up. We do not have a clear-cut explanation for this latter observation. Perhaps they should be seen in the light of the evolution of the PTH levels in the CC group, which also show a concomitant increase after 3 years. This might point to a preponderance of the underlying hyperparathyroid component with time on dialysis over the potential effects of calcium on PTH secretion. The data of the present study are in line with the experimental data indicating that lanthanum does not directly affect osteoblast number or activity [33].



   Conclusion
Top
 Abstract
 Introduction
 Methods
 Laboratory methods
 Results
 Discussion
 Conclusion
References
 
Lanthanum treatment results in a limited deposition of the element in bone. There is a slow release of lanthanum from its bone deposits 2 years after the arrest of the treatment and no association with aluminium-like bone toxicity. Bone lanthanum deposition is not related to the dose administered, indicating patient-related differences in gastrointestinal absorption.



   Acknowledgments
 
The authors thank Dirk De Weerdt for his excellent artwork. This research was supported by Shire Pharmaceutical Development.

Parts of this study were presented as posters at the 2002/2003 EDTA meeting (Nephrol Dial Transplant 2002; 17: S67; Nephrol Dial Transplant 2003; 18: S685–686); at ASN 2005 (J Am Soc Nephrol 2005; A741) and as an oral presentation at the 2003 ESAO meeting (Int J Artif Organs 2003; 26: A630) and free communication at the 2005 EDTA meeting (Nephrol Dial Transplant 2005; 20: v376).

Conflict of interest statement. None declared.



   References
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 Abstract
 Introduction
 Methods
 Laboratory methods
 Results
 Discussion
 Conclusion
 References
 

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Received for publication: 5. 3.06
Accepted in revised form: 8. 3.06


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