Parenteral aluminum administration in the dog: II. Induction of osteomalacia and effect on vitamin D metabolism

Abstract

There is an association between bone aluminum (A1) accumulation and dialysis-associated osteomalacia (OM). To study whether A1 is pathogenic in OM, quantitative bone histomorphometry was done in six dogs before (Bx 1) and after (Bx 2) 3 to 5 weeks of intravenous A1 administration (1 mg A1+++/kgday). Bone A1 was determined by histochemical and chemical methods. The percent osteoid rose from 2.8 ± 0.8 to 7.0 ± 4.3% (mean ± SD), P < 0.05, and osteoid width increased from 5.7 ± 0.6 to 8.0 ± 1.2 μ, P < 0.01, after A1. Bone A1 rose from 1.3 ± 1.6 to 94.0 ± 19.0 mg/kg after A1, and the severity of OM, expressed as either percent forming surface or percent osteoid, correlated with bone A1 measured histochemically and expressed as either percent surface or percent area of trabecular bone staining for A1 (r = 0.85, - 0.90, P < 0.01). Poor tetracycline uptake (sic dogs), which indicates impaired mineralization, and little or no separation of tetracycline labels (four dogs) were noted at Bx 2; thus, bone apposition and formation rates were below the limits of detection. Resorptive surface did not change but trabecular volume, expressed as percent of tissue volume, fell from 22.1 ± 3.0 to 17.1 ± 1.4%, P < 0.05. Serum levels of 1,25(OH)2D fell from 26.8 ± 9.1 to 4.5 ± 5.5 pg/ml after 17 days of A1; serum 25(OH)D levels were unchanged. These data indicate that A1 can cause OM and that its severity correlates with the bone A1 content. These findings suggests that A1 has a direct effect on bone; the role of altered vitamin D metabolism in mediating these changes remains to be defined.