Effects of daily treatment with parathyroid hormone 1-84 for 16 months on density, architecture and biomechanical properties of cortical bone in adult ovariectomized rhesus monkeys

Effects of daily treatment with parathyroid hormone 1-84 for 16 months on density, architecture and biomechanical properties of cortical bone in adult ovariectomized rhesus monkeys
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DOI:
10.1016/j.bone.2007.04.197
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发表时间:
2007-09-01
期刊:
影响因子:
4.1
通讯作者:
Smith, S. Y.
Smith, S. Y.
中科院分区:
医学2区
文献类型:
--
作者:
Fox, J.;Miller, M. A.;Smith, S. Y.

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用甲状旁腺激素1-84(PTH)或特立帕汀治疗可增加骨重塑,降低皮质骨(0)部位的骨矿物质密度(BMD),但也可能增加骨大小。BMD的降低和尺寸的增加对骨强度产生相反的影响。在成年卵巢切除(OVX)恒河猴中,我们评估了每日PTH治疗(5,10或25 μ g/kg)16个月对桡骨,胫骨和股骨骨干BMD的影响,以及对桡骨皮质骨和股骨骨干的生物力学特性(3点弯曲)的影响。PTH治疗并不影响双能X线骨密度仪测量胫骨骨干的面积BMD,但引起桡骨远端快速的剂量相关性降低。桡骨和股骨干的外周定量计算机断层扫描证实了主要由皮质面积增加引起的体积Ct.BMD的显著PTH剂量相关性降低。皮质厚度的显著增加是骨膜长度非显著增加和皮质内长度减少的结果。组织形态测定显示胫骨骨干和肋骨的皮质内骨形成增加,肋骨的哈弗氏重建增加,肋骨和胫骨的皮质孔隙率增加。股骨干的生物力学测试表明,PTH治疗对峰值载荷没有影响,但显著降低了刚度,增加了工作失败(骨折所需的能量)。桡侧皮质梁也发生了类似的变化,但只有刚度发生了显著变化。因此,PTH治疗OVX恒河猴降低骨密度和刚度的皮质骨,但不影响峰值负荷,可能是因为增加骨大小。然而,PTH治疗增加了股骨断裂所需的能量,使其更耐骨折。(C)2007爱思唯尔公司All rights reserved.
Treatment with parathyroid hormone 1-84 (PTH) or teriparatide increases osteonal remodeling and decreases bone mineral density (BMD) at cortical (0) bone sites but may also increase bone size. Decreases in BMD and increases in size exert opposing effects on bone strength. In adult ovariectomized (OVX) rhesus monkeys, we assessed the effects of daily PTH treatment (5, 10 or 25 mu g/kg) for 16 months on BMD at the radial, tibial and femoral diaphyses, and on biomechanical properties (3-point bending) of radial cortical bone and the femoral diaphysis. PTH treatment did not affect areal BMD measured by dual-energy X-ray absorptiometry at the tibial diaphysis but caused a rapid, dose-related decrease at the distal radial diaphysis. Peripheral quantitative computed tomography at the radial and femoral diaphyses confirmed a significant PTH dose-related decrease in volumetric Ct.BMD caused primarily by increased cortical area. Significant increases in cortical thickness were the result of nonsignificant increases in periosteal length and decreases in endocortical length. Histomorphometry revealed increased endocortical bone formation at the tibial diaphysis and rib, higher Haversian remodeling at the rib and increased cortical porosity at the rib and tibia. Biomechanical testing at the femoral diaphysis showed that PTH treatment had no effect on peak load, but significantly decreased stiffness and increased work-to-failure (the energy required to break the bone). Similar changes occurred in radial cortical beams but only stiffness was changed significantly. Thus, PTH treatment of OVX rhesus monkeys decreased BMD and stiffness of cortical bone but did not affect peak load, likely because of increased bone size. However, PTH treatment increased the energy required to break the femur making it more resistant to fracture. (C) 2007 Elsevier Inc. All rights reserved.