Parathyroid hormone sensitizes long bones to the stimulation of bone resorption by 1,25‐dihydroxyvitamin D₃

In response to hypocalcemia the serum PTH level increases rapidly followed by a PTH‐induced rise in 1,25‐dihydroxyvitamin D₃ [1,25‐(OH)₂D₃] production. Therefore, bone is first exposed to increased PTH levels before increased 1,25‐(OH)₂D₃ levels. In the present study the effect of pretreatment with PTH on 1,25‐(OH)₂D₃‐induced bone resorption was examined. Bone resorption was measured as release of prelabeled ⁴⁵Ca during culture from 17‐day‐old fetal mice radii/ulnae and metatarsals. Radii/ulnae and metatarsals are characterized by differences in development. In radii/ulnae mature osteoclasts are present, whereas in metatarsals only different stages of preosteoclasts can be found. Preincubation for 24 h but not 4 h with PTH increases the stimulation of bone resorption by 1,25‐(OH)₂D₃ in fetal radii/ulnae but not in metatarsals. Coincubation of PTH and 1,25‐(OH)₂D₃ did not result in a significant change in bone resorption compared to 1,25‐(OH)₂D₃ alone. The observed difference in the effect of pretreatment with PTH between radii/ulnae and metatarsals indicates that PTH does not stimulate the development of early osteoclast precursors but that a certain level of differentiation of the osteoclast precursor is required. Pretreatment with prostaglandin E₂ resulted in an effect similar to that of PTH. Inhibition of prostaglandin synthesis by indomethacin prevented the potentiation of 1,25‐(OH)₂D₃‐induced bone resorption by pretreatment with PTH. Thus, the present study demonstrates that PTH sensitizes responses to 1,25‐(OH)₂D₃. PTH must be present before 1,25‐(OH)₂D₃ to observe a potentiation of 1,25‐(OH)₂D₃‐induced bone resorption. Local production of prostaglandins seems to be involved in this action of PTH. Taken together, these data suggest that besides increased renal production of 1,25‐(OH)₂D₃ PTH also sensitizes bone for the 1,25‐(OH)₂D₃‐induced bone resorption.