Daily treatment with human recombinant parathyroid hormone-(1-34), LY333334, for 1 year increases bone mass in ovariectomized monkeys
Daily treatment with human recombinant parathyroid hormone-(1-34), LY333334, for 1 year increases bone mass in ovariectomized monkeys
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DOI：
10.1210/jc.84.10.3757
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发表时间：
1999-10-01
影响因子：
5.8
通讯作者：
Jerome, CP
中科院分区：
文献类型：
--
作者：
Brommage, R;Hotchkiss, CE;Jerome, CP
PTH刺激骨形成以增加大鼠和人类的骨量和强度。本研究的目的是确定重组人PTH-（1- 34）[rhPTH-（1-34）]对猴骨骼的影响，因为猴骨重建和结构与人骨相似。去卵巢组39只，每天皮下注射rhPTH-（1-34）1 μ g/kg，去卵巢组41只，每天皮下注射rhPTH-（1 - 34）5 μ g/kg，共12个月。测量全身骨矿物质含量，以及脊柱、胫骨近端、桡骨中段和桡骨远端的骨矿物质密度（BMD）。还分析了血清和尿液样本。rhPTH-（1-34）治疗不影响血清离子钙水平和尿钙排泄，但降低内源性PTH，同时增加血清骨化三醇水平。与OVX组相比，高剂量rkPTH-（1-34）使脊柱BMD增加14.3%，全身骨矿含量增加8.6%，胫骨近端BMD增加10.8%。亚区域分析表明，rhPTH-（1-34）对胫骨近端的合成代谢作用主要在松质骨。用较低剂量的rhPTH-（1-34）观察到对BMD的类似但不太显著的作用。每日皮下注射rhPTH-（1-34）1年可增加卵巢切除猴的BMD，而不诱导持续性高钙血症或高钙尿症。
PTH stimulates bone formation to increase bone mass and strength in rats and humans. The aim of this study was to determine the skeletal effects of recombinant human PTH-(1-34) [rhPTH-(1-34)] in monkeys, as monkey bone remodeling and structure are similar to those in human bone.Adult female cynomolgus monkeys were divided into sham-vehicle (n = 21), ovariectomized (OVX)-vehicle (n = 20), and OVX groups given daily sc injections of rhPTH-(1-34) at 1 (n = 39) or 5 (n = 41) mu g/kg for 12 months. Whole body bone mineral content was measured, as was bone mineral density (BMD) in the spine, proximal tibia, midshaft radius, and distal radius. Serum and urine samples were also analyzed. rhPTH-(1-34) treatment did not influence sei um ionized Ca levels or urinary Ca excretion, but depressed endogenous PTH while increasing serum calcitriol levels. Compared to that in the OVX group, the higher dose of rkPTH-(1-34) increased spine BMD by 14.3%, whole body bone mineral content by 8.6%, and proximal tibia BMD by 10.8%. Subregion analyses suggested that the anabolic effect of rhPTH-(1-34) on the proximal tibia was primarily in cancellous bone. Similar, but less dramatic, effects on BMD were observed with the lower dose of rhPTH-(1-34). Daily sc rhPTH-(1-34) treatment for 1 yr increases BMD in ovariectomized monkeys without inducing sustained hypercalcemia or hypercalciuria.