Bone repletion in vitro: evidence for a locally regulated bone repair response to PTH treatment

Normally bone formation and resorption are balanced by coupling, but in some conditions such as dietary Ca deficiency, bone resorption exceeds formation, resulting in bone loss (termed bone depletion in previous animal studies). When conditions causing depletion return to normal, a compensatory decrease in resorption and increase in formation occurs, leading to replacement of the lost bone. To test if this recovery process, termed bone repletion, might be locally regulated as in coupling we determined whether cellular and metabolic changes associated with repletion in vivo would occur in vitro in neonatal mouse calvaria. To increase resorption and decrease formation, serum-free cultures were treated with parathyroid hormone (10 nM bovine PTH1-84). Although formation was inhibited ([3H]proline incorporation into [3H]hydroxyproline), the number of bone cells increased during PTH treatment. To simulate repletion, PTH was removed after 3-9 days. Within 6 days of removal of PTH, resorption (osteoclast numbers and 45Ca release) decreased to control levels and bone formation increased to exceed untreated control levels. Autoradiographs of [3H]proline incorporation suggested an increase in the number of active bone forming cells (compared to untreated controls) after removal of PTH. These cellular and metabolic changes were similar to changes which occur during depletion and repletion in vivo. The results support the hypothesis that reversal of the resorptive processes initiated by PTH in organ cultures can occur in the absence of circulating factors. The apparent increase in the components of bone formation that were observed after PTH withdrawal may have resulted from generation of increased numbers of osteoblastic cells during PTH treatment.