Reduced deposition of aluminium in trabecular bone of uraemic rats treated with dihydroxylated vitamin D metabolites.
The rate of aluminium accumulation in bone may be related to the presence of vitamin D metabolites. The present study investigated the effect of 1,25(OH)2D3 (24 pmol/d s.c.) and 24R,25(OH)2D3 (480 pmol/day), combined or alone, on the deposition of aluminium (119 mumol/kg per day) in bone of uraemic rats during concomitant parenteral administration of aluminium for 9 weeks. Bone histomorphometry of trabecular bone revealed a severe low-turnover osteodystrophy in aluminium-treated uraemic rats, as evidenced by a decrease in osteoblastic osteoid surfaces and mineral apposition rates. 1,25(OH)2D3 as well as 24R,25(OH)2D3 decreased stainable bone aluminium and the aluminium content of trabecular bone and, in parallel, the number of osteoblasts and osteoclasts increased. Additional treatment with one or both vitamin D metabolites 14 days prior to the aluminium load further improved these results. Despite these effects, dynamic histomorphometric parameters remained suppressed and osteoidosis persisted. Serum PTH concentrations were significantly elevated in aluminium-loaded uraemic rats treated with 24R,25(OH)2D3 alone compared to controls. In conclusion, administration of 1,25(OH)2D3 or 24R,25(OH)2D3 reduces the accumulation of aluminium in trabecular bone in uraemic rats and prevents some of its excess toxicity. The mechanism of action may be different for either vitamin D metabolite; however, combined treatment does not result in further reduction of the accumulation rate of aluminium in bone in this model.
Ittel
T H
TH
Department of Internal Medicine II, RWTH, Aachen, FRG.
Hofstädter
F
F
Gladziwa
U
U
Sieberth
H G
HG
D015650:24,25-Dihydroxyvitamin D 3 / Q000627:therapeutic use*; D000535:Aluminum / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D002117:Calcitriol / Q000627:therapeutic use*; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D011292:Premedication; D051381:Rats; D011919:Rats, Inbred Strains; D014511:Uremia / Q000188:drug therapy* / Q000378:metabolism
D015650:24,25-Dihydroxyvitamin D 3; D000535:Aluminum; D002117:Calcitriol