Development and reversibility of impaired mineralization associated with lanthanum carbonate treatment in chronic renal failure rats.
BACKGROUND
We have previously shown that administration of the new phosphate binder lanthanum (La) carbonate at high doses during 12 weeks induces a mineralization defect (MD) in chronic renal failure (CRF) rats most likely due to the powerful phosphate binding. In this study, we want to investigate the fate and possible biological activities of La once it is accumulated in bone.


METHODS
CRF animals (5/6th nephrectomy) received La carbonate (2,000 mg/kg/day) via oral gavage for 2 or 6 weeks and were sacrificed immediately at the end of the treatment period and after a wash out period of 2 and 8 weeks. Bone histomorphometry and measurement of bone La content were performed. Control CRF animals received vehicle only.


RESULTS
After 2 weeks of La treatment, 75% of the animals showed signs of MD compared to 14% in CRF controls despite similar bone La levels. Two weeks after arrest of La treatment, bone La levels remained unchanged, yet 87% showed normal bone histology. A similar evolution was noted in the animals treated for 6 weeks. Bone histology showed a reduction of number of animals with a MD from 62.5% at 6 weeks of La treatment to 20% and 28% 2 and 8 weeks after arrest of La treatment respectively.


CONCLUSIONS
The phosphate-binder-induced MD may appear and disappear without any change in either the perimeter of active osteoblasts or in bone La levels. Bone histology in CRF animals normalized after arrest of the La administration, thereby presenting further arguments for the MD in La-treated animals to result from the high phosphate binding capacity of La rather than being the consequence of a direct effect of La on bone.
Bervoets
An R J
AR
Department of Medicine, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium.
Oste
Line
L
Behets
Geert J
GJ
Dams
Geert
G
Blust
Ronny
R
Marynissen
Rita
R
Geryl
Hilde
H
De Broe
Marc E
ME
D'Haese
Patrick C
PC
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002113:Calcification, Physiologic / Q000187:drug effects; D002118:Calcium / Q000097:blood / Q000652:urine; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000473:pathology*; D007811:Lanthanum / Q000097:blood / Q000494:pharmacology*; D008297:Male; D010710:Phosphates / Q000097:blood / Q000652:urine; D051381:Rats; D017208:Rats, Wistar
D010710:Phosphates; C119467:lanthanum carbonate; D007811:Lanthanum; D002118:Calcium