Abstract
The pharmacological actions of bisphosphonates
are due to the inhibitory effects on bone
resorption, but little is known about the bisphosphonate
action on bone formation. The purpose of
this study is to elucidate the actions of bisphosphonates,
clodronate, on bone formation in the
experimental in vivo and in vitro rat models. The
bone mineral density (BMD) was decreased in the
rats fed a low-calcium diet (0.05% Ca) for 6 days
compared with the rats fed a normal-calcium diet
(0.5% Ca). The decrease in BMD was suppressed in
the 2 mgP/day and the 4 mgP/day clodronate
administrations. Bone formation rate (BFR) in rats
fed a low-calcium diet was significantly increased
compared with the rats fed a normal-calcium diet,
and the 2 mgP clodronate administration further
increased the BFR. In the cultured rat bone marrow
cells, the area of mineralized nodules was significantly
increased at 10-7 and 10-6 M clodronate, but
high concentration of clodronate decreased the
area. From these results, it is concluded that clodronate
stimulates bone formation when the drug
was given to a rat with a relatively lower dose that
is sufficient to prevent bone resorption and that
this effect may be due to the stimulatory effect on
the differentiation process of osteoblasts.
