INCREASED BONE-FORMATION BY INTERMITTENT PARATHYROID-HORMONE ADMINISTRATION IS DUE TO THE STIMULATION OF PROLIFERATION AND DIFFERENTIATION OF OSTEOPROGENITOR CELLS IN BONE-MARROW

In order to examine the mechanism of the anabolic effect of parathyroi d hormone (PTH) on bone formation, human PTH(1-34) [hPTH(1-34)] (30 mu g/kg) was injected subcutaneously to 9-week-old rats 5 times a week f or 1 or 3 weeks. Trabecular bone volume (BV/TV) in the tibial metaphys is was not significantly different between the PTH- and vehicle-treate d groups, but the parameters related to bone formation, including oste oid surface (OS/BS), mineralizing surface (MS/BS), mineral apposition rate (MAR), and bone formation rate (BFR/BS), were significantly incre ased as early as 1 week after PTH treatment. And the parameters relate d to bone resorption including eroded surface (ES/BS) and osteoclast n umber (N.Oc/BS) were also significantly increased as early as 1 week a fter PTH treatment. Treatment with PTH for 1 week induced no significa nt increase in bone mineral density at the femoral metaphysis, whereas the same treatment for 3 weeks induced a significant increase. When b one marrow cells isolated from femora and tibiae of either PTH-or vehi cle-treated rats were cultured at a high density (2 x 10(7) cells/one well of 24-multiwell plate), cellular alkaline phosphatase (ALP) activ ity was significantly increased in the cells isolated from PTH-treated rats compared with vehicle-treated rats. When bone marrow cells were cultured at a low density (4 x 10(6) cells/a one well of 6-multiwell p late) to generate colonies (colony forming unit-fibroblastic, CFU-F), PTH induced apparent increases in both the total number of CFU-F and t he number of ALP-positive CFU-F. The ratio of the latter to the former was significantly higher in the PTH-treated group than in the vehicle -treated group. These findings suggest that the anabolic effect of PTH is, at least in part, due to the stimulation of proliferation and dif ferentiation of osteoprogenitor cells in bone marrow.