Effects of efficient phosphate binding on bone in chronic renal failure rats.
BACKGROUND
We recently reported that administration of high doses of lanthanum carbonate (1000 mg/kg/day) to chronic renal failure (CRF) rats can result in a mineralization defect. Our results suggested, however, that the impaired mineralization was not due to a direct toxic action of lanthanum on the bone, but rather was an indirect consequence of a phosphate depletion resulting from the compound's high phosphate-binding capacity. To further substantiate these results, in the present study, the effects of lanthanum carbonate on bone were compared to the effects of sevelamer, a nonabsorbed, non-metal-containing polymeric phosphate-binding agent.


METHODS
Male Wistar rats underwent a 5/6th nephrectomy to induce chronic renal failure, after which they were treated with either sevelamer (500 or 1000 mg/kg/day) or lanthanum carbonate (1000 mg/kg/day) by oral gavage for 12 weeks.


RESULTS
CRF animals treated with either sevelamer (500 or 1000 mg/kg/day) or lanthanum carbonate (1000 mg/kg/day) developed a phosphate depletion after 4 weeks of treatment, as evidenced by a marked reduction in phosphaturia. At sacrifice after 12 weeks of treatment, bone histomorphometry showed that a mineralization defect had developed in two out of six animals in the lanthanum-carbonate-treated group, in four out of seven animals in the 1000 mg/kg/ day sevelamer group, and in one out of nine animals in the 500 mg/kg/day sevelamer group.


CONCLUSIONS
These results corroborate our previous findings that the administration of a powerful phosphate-binding agent to CRF rats can induce phosphate depletion, resulting in a mineralization defect.
Behets
Geert J
GJ
Department of Nephrology, University of Antwerp, Universiteitsplein 1, Wilrijk B-2610, Belgium.
Gritters
Mareille
M
Dams
Geert
G
De Broe
Marc E
ME
D'Haese
Patrick C
PC
D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D004852:Epoxy Compounds / Q000009:adverse effects* / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000473:pathology; D007677:Kidney Function Tests; D007811:Lanthanum / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D009392:Nephrectomy / Q000379:methods; D010024:Osteoporosis / Q000139:chemically induced / Q000473:pathology; D010710:Phosphates / Q000097:blood / Q000378:metabolism*; D011073:Polyamines; D011095:Polyethylenes / Q000009:adverse effects* / Q000494:pharmacology; D011336:Probability; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D000069603:Sevelamer; D018709:Statistics, Nonparametric
D004852:Epoxy Compounds; D010710:Phosphates; D011073:Polyamines; D011095:Polyethylenes; C119467:lanthanum carbonate; D007811:Lanthanum; D000069603:Sevelamer