Effects of 1 alpha,25- and 24R,25-dihydroxyvitamin D3 on aluminum-induced rickets in growing uremic rats.
Rats were subjected to a two-stage subtotal nephrectomy or sham operation, and treated with aluminum (Al) or both aluminum and vitamin D3 metabolites for 5 weeks with a cumulative dose of 13.6 mg aluminum. Animals were injected with 3H-thymidine and 3H-proline. The following analyses were performed: quantitative histology of tibial metaphyses and cytomorphometric electron microscopy of osteoclasts, quantitative (ICP-spectroscopy) and qualitative determination (histochemical staining) of aluminum within organs, and serum biochemistry (Ca, P, Mg, vitamin D3 metabolites, alkaline phosphatase, urea). The following new facts of the aluminum-related bone disease became evident: (a) Application of aluminum to growing uremic rats induced rickets, whose major epiphyseal growth plate changes were 1 alpha,25(OH)2D3-dependent. Addition of 1 alpha,25(OH)2D3 prevented the formation of rachitic metaphysis, but failed to prevent osteoid accumulation on epiphyseal and metaphyseal trabecular surfaces. Moreover, calcitriol produced hyperosteoidosis and osteosclerosis in the same rats. Aluminum did not alter the function of osteoblasts, while osteoclasts seemed inactivated. (b) The development of rickets was associated with suppressed serum levels of 1,25(OH)2D3, reduced phosphorus level and the high content of aluminum in the bone, kidney, and liver. The addition of 24R,25(OH)2D3 markedly exaggerated the reduction of serum levels of calcitriol. We suggested that aluminum induces rickets in growing uremic rats, which consists of two components: vitamin D refractory osteomalacia and 1 alpha,25(OH)2D3-dependent epiphyseal growth plate changes.
D015650:24,25-Dihydroxyvitamin D 3; D000535:Aluminum / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001846:Bone Development; D001842:Bone and Bones / Q000187:drug effects / Q000503:physiopathology* / Q000648:ultrastructure; D002117:Calcitriol / Q000008:administration & dosage*; D004100:Dihydroxycholecalciferols / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012279:Rickets / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D013936:Thymidine; D014018:Tissue Distribution; D014511:Uremia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*
D004100:Dihydroxycholecalciferols; D015650:24,25-Dihydroxyvitamin D 3; D000535:Aluminum; D002117:Calcitriol; D013936:Thymidine