Unstable fractures are known to lead temporarily to bone mineral loss
in remote skeletal sites. The present study examines to what extent th
e healing of bone defects affects the mineralization of remote bone de
fects. Bilateral tibial defects were created in 20 female rats and fil
led with coralline implants (Interpore-200). Mineral content (MC) of t
he defects was followed nonivasively, 5 times during 57 days, using du
al X-ray absorptiometry. Different mineralization rates were experimen
tally obtained at the right tibial defects by impregnating the implant
s with different estradiol doses. We found that the mineralization rat
es in opposing defects were reciprocally coupled. Increased rates of d
efect mineralization induced by an adjacent fracture and local estradi
ol-effect, were accompanied by a decreased mineralization at the contr
alateral defect, and vice versa. The hypothesis that coupling between
remote bone defects was mediated by the circulation was tested by exam
ining the ability of the rats sera to stimulate osteogenic differentia
tion in cultured stromal cells. Sera of rats with low defect mineraliz
ation (without fractures) significantly increased osteogenic different
iation as indicated by increased specific phosphtase (ALP) activity. C
onversely sera of rats with high defect mineralization (with fractures
) failed to increase ALP activity. Sera fractionation showed that diff
erences in ALP induction may be attributed to macromolecules which are
yet unidentified. These results may suggest that remote bone defects
are utilizing systemic mineralization factors, in a competitive manner
.