Effect of flurbiprofen on hind-limb suspension-induced bone loss.
BACKGROUND
Prostaglandins, specifically prostaglandin E2 (PGE2), 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 PGE2 concentrations.


METHODS
A hind-limb suspension (HLS) technique was used to determine if FBP could attenuate the bone demineralization that occurs with decreased load-bearing activity. Rats were assigned to either the HLS group or the ground-based (control) group. Both of these groups were then divided into drug-treated and control subgroups (n = 10). Rats in the drug group received FBP 2 mg x kg(-1) x d(-1) subcutaneously. Study data were collected at 2 and 4 wk. The left femur of each animal was used for densitometry, 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 was not effective in protecting bone from the early stages of disuse osteopenia. 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% greater in the FBP-treated group than in the control group (p < 0.05). FBP did not significantly affect the mechanical properties of bone at either 2 or 4 wk.


CONCLUSIONS
FBP may not only affect bone demineralization by interacting with existing osteoclasts, but may also interfere with the signaling, activation, and recruitment of osteoclasts that occur after skeletal unloading.
Mitchell
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Ohio State University, Columbus, USA. matthew.mitchell@wpafb.af.mil
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000188:drug therapy*; D005480:Flurbiprofen / Q000494:pharmacology / Q000627:therapeutic use*; D019417:Hindlimb Suspension / Q000009:adverse effects*; D008297:Male; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005480:Flurbiprofen