Tissue and cellular basis for impaired bone formation in aluminum-related osteomalacia in the pig

• Published in: The Journal of clinical investigation 1987, Vol.79 (1), p.86-92
• Main Authors: SEDMAN, A. B, ALFREY, A. C, MILLER, N. L, GOODMAN, W. G
• Format: Article
• Language: English
• Subjects: Aluminum - metabolism; Aluminum - toxicity; Animals; Biological and medical sciences; Bone and Bones - metabolism; Bone Development - drug effects; Bone Matrix - pathology; Calcium - blood; Diseases of the osteoarticular system; Medical sciences; Osteoblasts - pathology; Osteomalacia - chemically induced; Osteomalacia - pathology; Osteoporosis. Osteomalacia. Paget disease; Phosphorus - blood; Swine; Tetracycline - pharmacology
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci112813

Bone formation is impaired in aluminum-associated bone disease. Reductions in the number of osteoblasts or in the function of individual osteoblasts could account for this finding. Thus, quantitative bone histology and measurements of bone formation were done at three skeletal sites in piglets given aluminum (Al) parenterally, 1.5 mg/kg per d, for 8 wk (Al, n = 4) and in control animals (C, n = 4). Bone Al was 241 +/- 40 mg/kg per dry weight in Al and 1.6 +/- 0.9 in C, P less than 0.001. All Al-treated animals developed osteomalacia with increases in osteoid seam width, osteoid volume, and mineralization lag time at each skeletal site, P less than 0.05 vs. C for all values. Mineralized bone formation at the tissue level was lower in Al than in C, P less than 0.05 for each skeletal site, due to reductions in active bone forming surface. Bone formation at the cellular level was similar in each group, however, and total osteoid production by osteoblasts did not differ in C and Al. Aluminum impairs the formation of mineralized bone in vivo by decreasing the number of active osteoblasts, and this change can be distinguished from the effect of aluminum to inhibit, either directly or indirectly, the calcification of osteoid.