Influence of lead on mineralization during bone growth.
Lead will inhibit skeletal development and localize in areas of bone formation and resorption, but the mechanisms of lead toxicity in bone are largely unknown. This study used an ectopic bone (plaque) induction method to investigate the effect of lead on mineralization of cartilage in growing bone. Demineralized bone matrix was subcutaneously implanted in male Long-Evans rats to induce plaque formation. Of 64 rats which were provided deionized water, 32 were implanted with control matrix (control group). The remaining 32 rats were implanted with matrix containing a target concentration of 200 micrograms lead/g of plaque tissue as ectopic bone (lead-added group). Another group of 32 rats was continuously exposed to 1000 ppm lead in drinking water and subcutaneously implanted with control matrix (drinking water-lead group). Plaques were taken for analysis on Days 8 and 12 postimplantation. Alkaline phosphatase activity and cartilage mineralization were obliterated in lead-added plaques. However, calcium deposition was markedly enhanced in the lead-added plaques. Decreased alkaline phosphatase in Day 8 drinking water-lead plaques followed increased Day 12 drinking water lead plaque calcification. Enhanced cartilage calcification and reduced alkaline phosphatase activity in the drinking water-lead plaques was consistent with effects observed in the metaphyseal regions of bone in lead-exposed rats and pigs. The results of this study suggest that lead adversely influences bone development through disruption of mineralization during growth.
Hamilton
J D
JD
Toxicology Department, Rohm and Haas Company, Spring House, Pennsylvania 19477, USA.
O'Flaherty
E J
EJ
D000469:Alkaline Phosphatase / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002113:Calcification, Physiologic / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D004435:Eating / Q000187:drug effects; D007854:Lead / Q000097:blood / Q000633:toxicity*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D010758:Phosphorus / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains
D010758:Phosphorus; D007854:Lead; D000469:Alkaline Phosphatase; D002118:Calcium