Sclerostin Antibody Treatment Improves Implant Fixation in a Model of Severe Osteoporosis
Sclerostin Antibody Treatment Improves Implant Fixation in a Model of Severe Osteoporosis
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DOI：
10.2106/jbjs.n.00654
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发表时间：
2015-01-21
影响因子：
5.3
通讯作者：
Sumner, Dale R.
中科院分区：
文献类型：
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作者：
Virdi, Amarjit S.;Irish, John;Sumner, Dale R.
背景：骨科和牙科植入物的机械固定会因骨体积减小而受到影响，如骨质疏松。在正常动物中，全身应用硬化素抗体(scl-Ab)可增强种植体固定。在本研究中，我们在一种已建立的骨质疏松的大鼠模型上测试了scl-Ab是否能改善种植体的固定。方法：我们使用了卵巢切除(OVX)的大鼠模型，在该模型中，我们发现在种植手术时，骨小梁体积减少了78%；Sham-OVX，年龄匹配的大鼠作为对照。在股骨远端髓腔内植入钛种植体后，大鼠被维持4、8或12周，并用scl-Ab或单独使用递送载体治疗两周。结果：SCL-Ab治疗使OVX组和OVX组的种植体固定强度增加了一倍，而OVX组则延迟了。SCL-Ab治疗还增强了骨与种植体的接触，增加了种植体周围骨小梁的厚度和体积，并增加了皮质厚度。这些结构变化与SCL-Ab治疗后骨形成率增加约五到七倍以及侵蚀表面50%的抑制有关。结论：在严重骨质疏松模型中，scl-Ab通过促进骨形成和抑制骨吸收来增强种植体固定，增加骨与种植体的接触，改善骨小梁的体积和结构。
Background: The mechanical fixation of orthopaedic and dental implants is compromised by diminished bone volume, such as with osteoporosis. Systemic administration of sclerostin antibody (Scl-Ab) has been shown to enhance implant fixation in normal animals. In the present study, we tested whether Scl-Ab can improve implant fixation in established osteoporosis in a rat model.Methods: We used an ovariectomized (ovx) rat model, in which we found a 78% decrease in trabecular bone volume at the time of implant surgery; sham-ovx, age-matched rats were used as controls. After placement of a titanium implant in the medullary cavity of the distal aspect of the femur, the rats were maintained for four, eight, or twelve weeks and treated biweekly with Scl-Ab or with the delivery vehicle alone. Outcomes were measured with use of microcomputed tomography, mechanical testing, and static and dynamic histomorphometry.Results: Scl-Ab treatment doubled implant fixation strength in both the sham-ovx and ovx groups, although the enhancement was delayed in the ovx group. Scl-Ab treatment also enhanced bone-implant contact; increased peri-implant trabecular thickness and volume; and increased cortical thickness. These structural changes were associated with an approximately five to sevenfold increase in the bone-formation rate and a >50% depression in the eroded surface following Scl-Ab treatment. Trabecular bone thickness and bone-implant contact accounted for two-thirds of the variance in fixation strength.Conclusions: In this model of severe osteoporosis, Scl-Ab treatment enhanced implant fixation by stimulating bone formation and suppressing bone resorption, leading to enhanced bone-implant contact and improved trabecular bone volume and architecture.