Determination of Growth Inhibitory Concentrations of Tetracycline for Bone in Organ Culture

Abstract

LONG bones of premature children given tetracycline in therapeutically high dosages have shown up to 40 per cent growth inhibition during 2–4 weeks of treatment¹. This effect was reversible, and approximately 2 weeks after the last administration of tetracycline the growth rate returned to normal. It is well known that large doses of tetracycline depress overall growth of chick embryos and mice², but in other studies when therapeutic doses of tetracycline were given to rats and humans, growth inhibition was not observed^3,4. It seemed probable that growth inhibition was dose dependent and that perhaps growth inhibiting concentrations of tetracycline could be reached in premature human infants, and so we decided to determine whether tetracycline would inhibit long bone growth in an organ culture system and, if so, at what concentration of tetracycline in the medium the inhibition occurred. The method developed by Proffit and Ackerman⁵, which evaluates growth of bone by measuring uptake of tritiated thymidine and of ¹⁴C proline from the culture medium, was used. Separate experiments indicated that, although there was some uptake of calcium-45 into bone spicules, there was no calcification of cartilage in this system. This culture method is similar to that used by Saxén^6–8, who observed effects of tetracycline on calcification of immature bone in vitro but did not describe an effect on growth.