Effects of parathyroid hormone on alkaline phosphatase activity and mineralization of cultured chick embryo tibiae.

Abstract

The objectives of this study were (a) to determine if decreased bone alkaline phosphatase (AlPase) activity, resulting either from exposure to parathyroid hormone (PTH) or from direct inhibition of AlPase with levamisole, was concomitant with net changes in bone Ca and P content; and (b) to determine the duration of the effect of PTH on bone AlPase activity after the hormone was removed. Tibiae from 7-day chick embryos were incubated in chemically defined medium for 3–4 days. The Ca and P content of bones incubated for 72 h in this system increased from 2-to 9-fold. Addition of PTH (1 U/ml) to the medium resulted in a 60% decrease in bone AlPase activity, and this decrease was accompanied by a marked inhibition of Ca and P accumulation in bone. When levamisole, a specific inhibitor of AlPase activity, was added to the medium, a similar inhibition of bone mineral accumulation resulted. A 24-h incubation in medium containing PTH (1 U/ml) resulted in a 30% decrease in bone AlPase activity. Following the 24-h exposure to PTH, incubation was continued in medium containing no hormone. After 72 h in hormone-free medium, bones that had been exposed to PTH earlier contained more AlPase activity than paired control bones never exposed to PTH. The PTH-treated bones also recovered their ability to accumulate Ca and P. The results of this study show that: (a) decreased bone AlPase activity resulting from either exposure to PTH or direct inhibition by levamisole is associated with a marked decrease in mineral accumulation in bone; (b) exposure to PTH followed by removal of the hormone leads to recovery and even an increase in bone AlPase activity; and (c) following removal of PTH from the culture system, tibiae recover their ability to accumulate Ca and P. These results suggest that one of the ways PTH may alter mineral accretion is through its effects on bone AlPase activity.