质子泵抑制剂FR167356对骨质疏松模型兔种植体骨整合的影响

Effects of proton pump inhibitor FR167356 on osseointegration of dental implant in osteoporosis rabbits

背景:破骨细胞质膜上的空泡型质子泵是骨组织溶解必不可少的关键酶,空泡型质子泵抑制剂对体外培养的破骨细胞有明显的抑制作用。目的:观察质子泵抑制剂FR167356对骨质疏松家兔种植体周围骨整合的影响。方法:将24只5月龄雌性家兔随机分成单纯卵巢切除组、质子泵抑制剂组及假手术组,每组8只,前2组家兔切除双侧卵巢,假手术组只切除卵巢周围等量的脂肪组织。卵巢摘除12周后,在所有家兔的双侧胫骨近心端各置入1枚纯钛种植体(长8 mm,直径3.3 mm)。质子泵抑制剂组在种植体周围肌注FR167356,其他2组肌注等量的生理盐水。在种植后4,12周进行X射线片、组织形态学观察及拔出力学实验。结果与结论:X射线片检查结果显示种植后第4周时,单纯卵巢切除组种植体的高阻射影像、种植体螺纹间隙的低密度影像、骨组织的界限明显比其他2组清楚;12周时,与单纯卵巢切除组相比,假手术组和质子泵抑制剂组种植体螺纹间隙的密度与周围骨组织更接近,种植体与周围骨组织的界限消失的更明显,2组无明显差异。组织学观察结果发现,4周时假手术组和质子泵抑制剂组种植体周围骨质多孔,平行于种植体表面的骨小梁排列紧密,小梁间连接较多,2组无明显差异;12周时假手术组和质子泵抑制剂组种植体周围骨组织量比4周时明显增加,骨小梁增粗且粗细均匀,连接紧密且间隙减小,单纯卵巢切除组没有观察到这种现象。在力学实验中,第4,12周,单纯卵巢切除组的最大拔出力值明显低于其他2组。提示局部应用质子泵抑制剂FR167356对骨质疏松家兔种植体骨整合有显著的促进作用。

BACKGROUND：Vacuolar proton pump on the cytoplasmic membrane of osteoclasts is an essential enzyme for bone histolysis. Vacuolar proton pump inhibitor can significantly inhibit the in vitro cultured osteoclasts. OBJECTIVE：To observe the effect of proton pump inhibitor FR167356 on the osseointegration of dental implant of osteoporosis rabbits. METHODS：A total of 24 female Japanese white rabbits aged 5 months were randomly divided into three groups：ovariectomy （OVX） group, FR167356 group and shamed operation group. Each group contained eight rabbits. Rabbits of OVX group and FR167356 group received a surgical removal of bilateral ovaries, while rabbits of sham operation group had a surgical removal of equivalent adipose tissue beside the ovaries. Two titatium implants（8 mm long, 3.3 mm diameter） were instal ed into bilateral proximal tibias respectively 12 weeks after OVX operation. FR167356 was administrated by muscle injection in FR167356 group;meanwhile equivalent normal saline was administrated in the OVX group and sham operation group. At 4 and 8 weeks after implantation, animals in each group were sacrificed respectively for X-ray imaging, histomorphology, and mechanical test. RESULTS AND CONCLUSION：X-ray examination showed that at 4 weeks, the implants in the OVX group exhibited a high resistance projective image, low density image of clearance screw thread, and clear boundaries between bone tissue than the other two group. At 12 weeks, the density of the clearance screw thread in sham operation group and FR167356 group was more closer to the surrounding bone tissue when compared with the OVX group, the boundaries between the implant and the surrounding bone tissue disappeared more apparently, and no significant differences were found between the two groups. Histomorphology observation revealed that, at 4 weeks after implantation, new bone with porous and trabecular extended along the implant surface to the root direction in FR167356 and sham operation groups. There were no significant differences in the two groups. At 12 weeks after implantation, the bone mass around implant was increased greatly and the trabecular grew thicker. This phenomenon was not observed in the OVX group. Mechanic test showed that at 4 and 12 weeks after implantation, the maximum pul out force in the OVX group was significantly lower than that in the other two groups. Local application of FR167356 can significantly improve the osseointegration of the implant in osteoporosis rabbits.