Mitchell M E, Stern L S, Shah N, Ostrum R
Ohio State University, Columbus, USA.
Aviat Space Environ Med. 2001 Sep;72(9):790-3.
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.
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.
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.
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.
前列腺素,特别是前列腺素E2(PGE2),可能与微重力环境下发生的骨质流失有关。氟比洛芬(FBP)是一种非甾体抗炎药(NSAID),已被证明可提高大鼠骨膜附着率,并可能通过降低PGE2浓度来抑制骨质流失。
采用后肢悬吊(HLS)技术来确定FBP是否能减轻因承重活动减少而发生的骨质脱矿。将大鼠分为HLS组或地面(对照)组。然后将这两组再分为药物治疗和对照亚组(n = 10)。药物组的大鼠皮下注射2 mg x kg(-1) x d(-1)的FBP。在第2周和第4周收集研究数据。每只动物的左股骨用于骨密度测量,右胫骨用于组织形态计量学分析。通过三点弯曲评估左股骨的力学性能。
2周后,HLS组和地面组中接受FBP治疗的大鼠骨矿物质密度(BMD)均比对照组低6%(p < 0.05)。FBP在保护骨骼免受废用性骨质减少早期影响方面无效。在第4周时,地面组中对照动物和药物治疗动物的BMD无显著差异。然而,在HLS组中,FBP治疗组的BMD比对照组高11%(p < 0.05)。FBP在第2周或第4周时均未显著影响骨骼的力学性能。
FBP不仅可能通过与现有的破骨细胞相互作用来影响骨质脱矿,还可能干扰骨骼卸载后发生的破骨细胞信号传导、激活和募集。