Localization of lanthanum in bone of chronic renal failure rats after oral dosing with lanthanum carbonate.
BACKGROUND
Lanthanum carbonate has been shown to be a safe, effective phosphate-binding agent. We have shown that an impaired mineralization in chronic renal failure rats treated with high doses of lanthanum carbonate develops secondary to phosphate depletion and is therefore pharmacologically mediated rather than a direct effect of lanthanum on bone. Although bulk bone lanthanum concentrations are low, it is important to consider the localization within a given tissue.


METHODS
Using the scanning x-ray micro-fluorescence set-up at beamline ID21 of the European Synchrotron Radiation Facility, calcium and lanthanum distributions in bone samples were mapped.


RESULTS
In chronic renal failure rats loaded orally with lanthanum carbonate (12 weeks) (2000 mg/kg/day), bulk bone lanthanum concentrations reached values up to 5 microg/g wet weight. Lanthanum could be demonstrated at the edge of the mineralized bone, at both actively mineralizing and quiescent sites, independent of the type of bone turnover. In the presence of hyperparathyroid bone disease, lanthanum was also distributed throughout the mineralized trabecular bone. No correlation with the presence of osteoid, or the underlying bone pathology could be demonstrated. After a 2- or 4-week washout period before sacrifice, lanthanum localization did not change significantly.


CONCLUSIONS
The comparable localization of lanthanum in different types of bone turnover, and the unchanged localization after washout and consequent disappearance of the mineralization defect, indicates no relationship between the localization of lanthanum in bone and the presence of a mineralization defect.
Behets
Geert J
GJ
Department of Nephrology-Hypertension, University of Antwerp, Antwerp, Belgium.
Verberckmoes
Steven C
SC
Oste
Line
L
Bervoets
An R
AR
Salomé
Murielle
M
Cox
Alan G
AG
Denton
John
J
De Broe
Marc E
ME
D'Haese
Patrick C
PC
D000284:Administration, Oral; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism*; D007811:Lanthanum / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D008297:Male; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013052:Spectrometry, X-Ray Emission; D014018:Tissue Distribution
D010710:Phosphates; C119467:lanthanum carbonate; D007811:Lanthanum