Intermittent Administration of Parathyroid Hormone [1-34] Prevents Particle-Induced Periprosthetic Osteolysis in a Rat Model.
Intermittent Administration of Parathyroid Hormone [1-34] Prevents Particle-Induced Periprosthetic Osteolysis in a Rat Model.
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DOI：
10.1371/journal.pone.0139793
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Yan S
中科院分区：
文献类型：
--
作者：
Bi F;Shi Z;Zhou C;Liu A;Shen Y;Yan S
我们在大鼠模型中检查了间歇性给予甲状旁腺激素（PTH[1-34]; 60 μg/kg/天）是否可以预防钛（Ti）颗粒对植入物固定和假体周围骨质溶解的负面影响。18只成年雄性大鼠（12周龄，骨骼仍在生长）双侧股骨植入髓内钛植入物;空白组6只大鼠接受溶剂注射，对照组和PTH治疗组12只大鼠在手术时接受钛颗粒注射，术后2周和4周关节内注射。接受PTH组Ti颗粒的6只大鼠也接受PTH[1-34]治疗。术后6周，收集所有标本进行X线、显微CT、生物力学、扫描电子显微镜（SEM）和动态组织形态计量学评估。与空白组相比，对照组的BMD、BV/TV、Tb.N、最大固定强度和矿物沉积率均较低，表明已成功建立了假体周围骨溶解模型。与对照组相比，PTH[1-34]给药显著增加了PTH组股骨远端的骨密度、BV/TV、Tb.N、Tb.Th、Tb.Sp、Con.D、SMI和最大固定强度。扫描电镜显示PTH组的骨-种植体接触率、板层骨厚度和骨小梁面积均高于对照组。与空白组和对照组相比，在PTH组中观察到更高的矿物质沉积率。这些发现表明，间歇性给予PTH[1-34]可通过促进骨形成来预防假体周围骨溶解。在大鼠中，以超药理学剂量评价了PTH[1-34]的作用;因此，需要进行额外的研究以证明其在假体周围骨质溶解中的治疗潜力。
We examined whether intermittent administration of parathyroid hormone (PTH[1–34]; 60 μg/kg/day) can prevent the negative effects of titanium (Ti) particles on implant fixation and periprosthetic osteolysis in a rat model. Eighteen adult male rats (12 weeks old, bones still growing) received intramedullary Ti implants in their bilateral femurs; 6 rats from the blank group received vehicle injections, and 12 rats from the control group and PTH treatment group received Ti particle injections at the time of operation and intra-articular injections 2 and 4 weeks postoperatively. Six of the rats that received Ti particles from the PTH group also received PTH[1–34] treatment. Six weeks postoperatively, all specimens were collected for assessment by X-ray, micro-CT, biomechanical, scanning electron microscopy (SEM), and dynamic histomorphometry. A lower BMD, BV/TV, Tb.N, maximal fixation strength, and mineral apposition rate were observed in the control group compared to the blank group, demonstrating that a periprosthetic osteolysis model had been successfully established. Administration of PTH[1–34] significantly increased the bone mineral density of the distal femur, BV/TV, Tb.N, Tb.Th, Tb.Sp, Con.D, SMI, and maximal fixation strength in the PTH group compared to that in the control group. SEM revealed higher bone–implant contact, thicker lamellar bone, and larger trabecular bone area in the PTH group than in the control group. A higher mineral apposition rate was observed in the PTH group compared to both the blank and control groups. These findings imply that intermittent administration of PTH[1–34] prevents periprosthetic osteolysis by promoting bone formation. The effects of PTH[1–34] were evaluated at a suprapharmacological dosage to the human equivalent in rats; therefore, additional studies are required to demonstrate its therapeutic potential in periprosthetic osteolysis.