Does the phosphate binder lanthanum carbonate affect bone in rats with chronic renal failure?
Adequate control of phosphate levels remains an important issue in patients with chronic renal failure (CRF). Lanthanum carbonate has been proposed as a new phosphate binder. Previous studies have shown a high phosphate binding capacity (>97%) and low gastrointestinal absorption of lanthanum, without serious toxic side effects in the presence of a normal renal function (NRF). Because of lanthanum's physicochemical resemblance to calcium, the possible effects of it on bone have to be considered. The aim of this study was to investigate the effects of lanthanum carbonate on bone histology in NRF and CRF rats after oral administration of the compound with doses of 100, 500, or 1000 mg/kg per d for 12 wk. Bone histomorphometry showed that CRF animals that received vehicle developed secondary hyperparathyroidism. Urinalysis of lanthanum-loaded CRF animals showed a dose-dependent decrease in urinary phosphorus excretion, which was clearly more pronounced in the CRF groups compared with NRF animals. Phosphatemia, however, remained normal. Lanthanum carbonate administration induced a dose-dependent decrease in bone formation rate and increase in osteoid area in CRF animals. Three of seven animals in the CRF-1000 group and one of eight animals in the NRF-100 group were classified as having a mineralization defect. The number of cuboidal osteoblasts, however, was not affected, indicating that bone changes were not due to a toxic effect of lanthanum on the osteoblast. Furthermore, lanthanum concentrations in the femur remained low and did not correlate with histomorphometric parameters. These findings suggest that the administration of high doses of phosphate binder (1000 mg/kg per d lanthanum carbonate), in combination with decreased 25-(OH) vitamin D(3) in the uremic state, resulted in phosphate depletion and followed by an increased mobilization of phosphorus out of bone and/or reduced incorporation into bone. There was no evidence that lanthanum had a direct toxic effect on osteoblasts.
Department of Nephrology-Hypertension, University of Antwerp, Belgium.
Geert J
GJ
Behets
Geert
G
Dams
Sven R
SR
Vercauteren
Stephen J
SJ
Damment
Roger
R
Bouillon
Marc E
ME
De Broe
Patrick C
PC
D'Haese
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001847:Bone Diseases / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000097:blood; D004435:Eating; D007676:Kidney Failure, Chronic / Q000150:complications*; D007811:Lanthanum / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D010006:Osteoblasts / Q000187:drug effects; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000378:metabolism*; D010758:Phosphorus / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D014807:Vitamin D / Q000097:blood
D010281:Parathyroid Hormone; D010710:Phosphates; D015675:Osteocalcin; D014807:Vitamin D; D010758:Phosphorus; C119467:lanthanum carbonate; D007811:Lanthanum; D003404:Creatinine; D000469:Alkaline Phosphatase; D002118:Calcium