Kurth A H A, Eberhardt C, Müller S, Steinacker M, Schwarz M, Bauss F
Department of Orthopaedic Surgery, University Hospital Frankfurt, Marienburgstr. 2, 60528 Frankfurt/Main, Germany.
Bone. 2005 Aug;37(2):204-10. doi: 10.1016/j.bone.2004.12.017.
Osteoporosis is known to impair the process of implant osseointegration. Bisphosphonates are drugs that inhibit osteoclast-mediated bone resorption and normalize the high rate of bone turnover that characterizes this disease. Consequently, there is a rationale for using bisphosphonates to enhance the early stabilization of implants in subjects with low bone mass. In this study, 84 rats received titanium-only or hydroxyapatite (HA)-coated titanium femoral implants, 3 months after being ovariectomized (OVX) or sham operated. They were then treated for 4 weeks. The OVX rats were randomly assigned to daily subcutaneous injections of either saline or the bisphosphonate ibandronate (at a dose of 1 microg/kg or 25 microg/kg), while the sham-operated animals received saline throughout. The 1 microg/kg or 25 microg/kg ibandronate doses are considered translatable to doses used to treat osteoporosis and metastatic bone disease (MBD), respectively, in rats, and roughly reflect those used in humans. At the end of the treatment period, bone mineral density (BMD) at the lumbar spine increased in both of the ibandronate-treated groups when compared with the OVX control animals and to a level similar to that of the sham-operated control group. Osseointegration, determined by histomorphometric analysis and expressed as percentage of osseointegration implant surface (OIS), did not differ between groups for the titanium-only implants. For the HA-coated implants, however, OIS was 113.5% and 185% higher in the groups receiving 1 microg/kg or 25 microg/kg ibandronate, respectively, relative to the OVX controls. In turn, the OIS of the HA-coated implants was 56.5% lower in the OVX control group than in the sham control group. These findings clearly demonstrate that OVX-induced osteopenia impairs the osseointegration of HA-coated titanium implants and that ibandronate, administered at doses analogous to those used to clinically treat osteoporosis and MBD, counters this harmful effect. Ibandronate may, therefore, have a role in improving the osseointegration of implants in patients with osteoporosis and MBD.
已知骨质疏松会损害种植体骨整合过程。双膦酸盐类药物可抑制破骨细胞介导的骨吸收，并使这种疾病所特有的高骨转换率恢复正常。因此，有理由使用双膦酸盐来增强低骨量受试者种植体的早期稳定性。在本研究中，84只大鼠在卵巢切除（OVX）或假手术后3个月，接受了仅含钛或羟基磷灰石（HA）涂层的钛股骨种植体。然后对它们进行4周的治疗。OVX大鼠被随机分配为每日皮下注射生理盐水或双膦酸盐伊班膦酸钠（剂量为1微克/千克或25微克/千克），而假手术动物全程接受生理盐水注射。1微克/千克或25微克/千克的伊班膦酸钠剂量分别被认为可转化为用于治疗大鼠骨质疏松症和转移性骨病（MBD）的剂量，并且大致反映了人类使用的剂量。在治疗期结束时，与OVX对照动物相比，两个伊班膦酸钠治疗组的腰椎骨矿物质密度（BMD）均有所增加，且达到了与假手术对照组相似的水平。通过组织形态计量分析确定并以骨整合种植体表面（OIS）百分比表示的骨整合，在仅含钛种植体的各组之间没有差异。然而，对于HA涂层种植体，相对于OVX对照组，接受1微克/千克或25微克/千克伊班膦酸钠的组中OIS分别高出113.5%和185%。反过来，HA涂层种植体在OVX对照组中的OIS比假手术对照组低56.5%。这些发现清楚地表明，OVX诱导的骨质减少会损害HA涂层钛种植体的骨整合，而以类似于临床治疗骨质疏松症和MBD的剂量给药的伊班膦酸钠可对抗这种有害作用。因此，伊班膦酸钠可能在改善骨质疏松症和MBD患者种植体的骨整合方面发挥作用。
