Effect of Flurbiprofen on Hind-Limb Suspension- Induced Bone Loss

Matthew E. Mitchell, M.D., Lawrence S. Stern, Ph.D., Nilesh Shah, M.D., and Robert Ostrum, M.D.
Aviat Space Environ Med 2001; 72:790-3

Abstract

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 · kg^-1 · 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. Conclusion: 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.

Keywords: bone loss, hind limb suspension, NSAID.

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Table of Contents for Volume 72, Number 9 of the ASME journal.