Six Weeks of Daily Abaloparatide Treatment Increased Vertebral and Femoral Bone Mineral Density, Microarchitecture and Strength in Ovariectomized Osteopenic Rats.
Six Weeks of Daily Abaloparatide Treatment Increased Vertebral and Femoral Bone Mineral Density, Microarchitecture and Strength in Ovariectomized Osteopenic Rats.
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DOI：
10.1007/s00223-016-0171-1
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发表时间：
2016-11
影响因子：
4.2
通讯作者：
Hattersley, Gary
中科院分区：
文献类型：
--
作者：
Bahar, Hila;Gallacher, Kyla;Downall, Julie;Nelson, Carol A.;Shomali, Maysoun;Hattersley, Gary
阿巴拉肽是一种新的、有效的、选择性的甲状旁腺激素受体1激活剂，正在临床开发中，用于治疗骨质疏松症。我们评估了6周的阿巴拉肽对去卵巢(OVX)大鼠骨量、微结构、质量和强度的影响。术后8周去骨量(基线)后，OVX大鼠(n=20~21只/组)每日皮下注射5或20µg/kg的阿巴拉帝或OVX-Veh。假手术对照组大鼠24只。分别于基线和治疗6周后测量腰椎(L4)、全股骨和股骨骨干的面骨密度(ABMD)。在治疗阶段结束时评估股骨和椎骨的结构和力学性能。在基线水平，OVX-Veh大鼠的aBMD显著低于Sham对照组。给予去卵巢大鼠5或20微克/公斤/天的阿巴拉肽治疗后，腰椎、全股骨和股骨骨干的BMD增加到超过OVX-Veh或Sham对照组的水平，并呈剂量依赖性。与OVX载体相比，阿巴拉肽5和20µg/kg组小梁微结构得到改善，腰椎小梁BV/TV分别超过OVX-Veh对照组57%和78%，股骨远端BV/TV分别增加145%和270%。阿巴拉帝20µg/kg组大鼠股骨骨干皮质体积和厚度明显大于去卵巢对照组和假手术对照组。与OVX-Veh对照组相比，OVX-ABL组股骨骨干、股骨颈和L4椎体的骨强度参数明显改善。骨量-强度关系和估计的内在强度特性表明使用阿巴拉肽维持或改善了骨质量。这些数据表明，骨量减少的去卵巢大鼠通过阿巴罗帕肽治疗进行骨骼修复，与改善骨小梁微结构、皮质几何形状和与骨质疏松症患者有临床相关性的部位的骨强度有关。
Abaloparatide is a novel, potent and selective activator of parathyroid hormone receptor 1 (PTHR1) under clinical development for the treatment of osteoporosis. We assessed the effect of 6 weeks of abaloparatide on bone mass, microarchitecture, quality and strength in ovariectomized (OVX) rats. After 8 weeks of post-surgical bone depletion (baseline), OVX rats (n = 20–21/group) received daily subcutaneous vehicle (OVX-Veh) or abaloparatide at 5 or 20 µg/kg. Sham-operated control rats (n = 24) received vehicle. Areal bone mineral density (aBMD) of the lumbar spine (L4), total femur and femur diaphysis was measured at baseline and after 6 weeks of treatment. Femur and vertebral bone architecture and mechanical properties were assessed at the end of the treatment phase. At baseline, OVX-Veh rats exhibited significantly lower aBMD relative to Sham controls. Treatment of OVX rats with abaloparatide at 5 or 20 µg/kg/day increased aBMD dose-dependently in the lumbar spine, total femur and femur diaphysis to levels exceeding OVX-Veh or Sham controls. The abaloparatide 5 and 20 µg/kg groups had improved trabecular microarchitecture relative to OVX vehicle, with trabecular BV/TV exceeding OVX-Veh control values by 57 and 78 % (respectively) at the lumbar spine, and by 145 and 270 % at the distal femur. Femur diaphyseal cortical volume and thickness were significantly greater in the abaloparatide 20 µg/kg group relative to OVX vehicle or Sham controls. Bone strength parameters of the femur diaphysis, femur neck and L4 vertebra were significantly improved in the OVX-ABL groups relative to OVX-Veh controls. Bone mass–strength relationships and estimated intrinsic strength properties suggested maintained or improved bone quality with abaloparatide. These data demonstrate skeletal restoration via abaloparatide treatment of osteopenic OVX rats, in association with improved trabecular microarchitecture, cortical geometry and bone strength at sites that have clinical relevance in patients with osteoporosis.
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影响因子：
4.1
作者：
Kabel, J;Odgaard, A;Huiskes, R
通讯作者：
Huiskes, R
影响因子：
6.2
作者：
Recker, Robert R.;Marin, Fernando;Stepan, Jan
通讯作者：
Stepan, Jan
影响因子：
5.8
作者：
Horwitz, Mara J.;Tedesco, Mary Beth;Stewart, Andrew F.
通讯作者：
Stewart, Andrew F.
影响因子：
--
作者：
Dean, T;Linglart, A;Gardella, TJ
通讯作者：
Gardella, TJ
影响因子：
6.2
作者：
Burge, Russel;Dawson-Hughes, Bess;Tosteson, Anna
通讯作者：
Tosteson, Anna