title: Short-term aluminum administration in the rat: reductions in bone formation without osteomalacia.
abstract: Aluminum may be a pathogenic factor in dialysis-associated osteomalacia. To study the early effects of AI on bone, cortical bone growth was measured in pair-fed rats given Al and control rats over two consecutive intervals of 28 (period I) and 16 (period II) days, respectively, using tetracycline labeling of bone. Al (2 mg elemental Al per rat) was administered intraperitoneally for 5 days each week, except for the first week of study, when an incremental dose of Al was given. Control rats received saline vehicle only. For the entire 44-day study, bone and matrix formation were reduced from control values in rats given Al. Although bone and matrix formation remained at control levels during period I in rats given Al, both measurements decreased from control values during period II. During Al exposure, bone and matrix apposition at the periosteum were reduced from control levels in period II, but not in period I. Neither osteoid width nor mineralization front width increased from control values in rats given Al. These findings indicate that Al reduces bone and matrix formation early in the course of Al exposure and prior to the development of histologic osteomalacia. Rather than acting as an inhibitor of mineralization, the early effect of Al on bone is the suppression of matrix synthesis. Our results suggest that the state of low bone formation seen in dialysis-associated osteomalacia may be the consequence of a direct toxic effect of Al on the cellular activity of osteoblasts.
mesh_terms: D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D001857:Bone Matrix / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010006:Osteoblasts / Q000187:drug effects; D010018:Osteomalacia / Q000139:chemically induced*; D010521:Periosteum / Q000187:drug effects; D051381:Rats; D006435:Renal Dialysis / Q000009:adverse effects; D013754:Tetracyclines / Q000494:pharmacology; D013977:Tibia / Q000473:pathology; D013997:Time Factors
chemical_list: D013754:Tetracyclines; D000535:Aluminum