In this study, we have determined the effect of the divalent strontium
salt S12911 on bone cell replication and bone formation in two cultur
e systems. In the first series of experiments, half-calvariae of newbo
rn rats were cultured with S12911 from 24 to 96 h and labeled with H-3
-thymidine for the last 6 h of culture or treated with S12911 for 24 h
and labeled for 24 h with H-3-proline 24-48 h after the removal of th
e agent, Calvariae were then processed for histomorphometry, S12911 at
10(-3) M increased the replication of preosteoblastic cells by 30-50%
after 24 h and by 60% after 96 h of treatment. This effect was specif
ic, since the number of labeled osteoblasts and of periosteal cells wa
s not changed, A transient 24 h treatment with S12911 at 10(-3) M incr
eased bone formation 24 and 48 h after the removal of the agent, H-3-p
roline labeled surfaces and bone formation rates were increased by 20%
-35%. In the second series of experiments, sequential collagenase dige
stions were used to isolate cell populations enriched in fibroblasts o
r osteoblasts (Ob) from 22 day fetal rat calvariae. Treatment with S12
981 at 10(-3) M for 24 h enhanced DNA synthesis by three- to fourfold
in cell populations enriched in fibroblasts and preosteoblastic cells.
The effect was less pronounced and inconsistent in Ob cells, S12911 a
t 10(-3) M for 24 h also increased collagen and noncollagen protein sy
nthesis by 35% in Ob cells. These data indicate that the divalent stro
ntium salt S12911 enhances bone cell replication and bone formation in
vitro, an effect that may contribute to the previously reported effec
ts of S12911 on trabecular bone mass in vivo.