The effects of cadmium, copper or zinc on formation of embryonic chick bone in tissue culture.

Femurs from 9-day-old chick embryo were cultivated for 6 days by the roller-tube method in the presence of Cd, Cu or Zn. Cd (5.0 microM and above) and Cu (2.5 microM and above) caused a decrease in collagen content of both diaphysis and epiphysis, mainly due to inhibition of collagen synthesis. In addition, Cd and Cu each showed a tendency to inhibit an increase in Ca content of diaphysis, where intraperiosteal ossification could be observed. Alkaline phosphatase (ALP) activity was decreased by Cd (5.0 microM and above) or Cu (10 microM and above) in diaphysis. On the other hand, Zn at 50 microM and above inhibited an increase in Ca content of the diaphysis with a remarkable elevation of ALP activity in the medium. At this time, Zn did not decrease the collagen content of the diaphysis so strongly. Histological observations revealed that Cd and Cu each decreased both calcified and uncalcified osteoid tissue at 2.5 microM, while Zn at 100 microM decreased calcified tissue but increased uncalcified osteoid tissue. As Zn accumulated particularly in diaphysis and deposited at the edge of calcified tissue, it was suggested that Zn inhibited calcification physicochemically. It was concluded that Cd or Cu would induce bone damage represented by osteoporosis, whereas Zn would induce osteomalacia.