Background: Prostaglandins, specifically prostaglandin E-2 (PGE(2)), may be
involved in the bone loss that occurs in microgravity. Flurbiprofen (FBP),
a nonsteroidal anti-inflammatory drug (NSAID), has been shown to increase
periosteal apposition rate in rats, and may inhibit bone loss by decreasing
PGE(2) concentrations. Methods: A hind-limb suspension (HLS) technique was
used to determine if FBP could attenuate the bone demineralization that oc
curs with decreased load-bearing activity. Rats were assigned to either the
HLS group or the ground-based (control) group. Both of these groups were t
hen divided into drug-treated and control subgroups (n - 10). Rats in the d
rug group received FBP 2 mg . kg(-1) . d(-1) subcutaneously. Study data wer
e collected at 2 and 4 wk. The left femur of each animal was used for densi
tometry, and the right tibia was processed for histomorphometry. Mechanical
properties of the left femur were assessed by three-point bending. Results
: After 2 wk, the FBP-treated rats in both the HLS and ground-based groups
had 6% less bone mineral density (BMD) than did controls (p < 0.05). FBP wa
s not effective in protecting bone from the early stages of disuse osteopen
ia. At 4 wk, BMD in the ground-based group was not significantly different
between control and drug animals. However, in the HLS group, BMD was 11% gr
eater in the FBP-treated group than in the control group (p < 0.05). FBP di
d not significantly affect the mechanical properties of bone at either 2 or
4 wk. Conclusion. FBP may not only affect bone demineralization by interac
ting with existing osteoclasts, but may also interfere with the signaling,
activation, and recruitment of osteoclasts that occur after skeletal unload
ing.