Treatment with human parathyroid hormone (1-34) for 18 months increases cancellous bone volume and improves trabecular architecture in ovariectomized cynomolgus monkeys (Macaca fascicularis)
Treatment with human parathyroid hormone (1-34) for 18 months increases cancellous bone volume and improves trabecular architecture in ovariectomized cynomolgus monkeys (Macaca fascicularis)
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DOI：
10.1016/s8756-3282(00)00430-0
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发表时间：
2001-02-01
期刊：
影响因子：
4.1
通讯作者：
Brommage, R
中科院分区：
文献类型：
--
作者：
Jerome, CP;Burr, DB;Brommage, R
绝经后骨质疏松症的一个关键特征是骨小梁质量和连接性的丧失。目前的研究重点是这些参数在评估长期（12和18个月）甲状旁腺激素（PTH）治疗和其撤销（6个月）在卵巢切除食蟹猴（食蟹猴），一个良好的表征模型与绝经后骨质疏松症相关的骨变化。我们使用静态和动态组织形态计量学参数来评估四个临床上重要的腰椎骨折部位（包括腰椎、股骨颈、桡骨远端和髂嵴）松质骨的数量和结构。将重组人PTH（1 - 34）以每天1.0 μ g/kg（n = 19）和每天5.0 μ g/kg（n = 21）的剂量每天给予两组，持续18个月。为了研究PTH停药的影响，两组以每天1.0 μ g/kg（n = 20）和每天5.0 μ g/kg（n = 20）的剂量每天给予PTH（1 - 34），持续12个月，随后每天给予赋形剂，持续6个月。假卵巢切除组和卵巢切除（ovx）组每天接受溶媒注射，持续18个月。在研究的时间点，PTH治疗对骨形成率的影响很小，但在6个月和15个月的髂嵴活检中，以及在18个月后的腰椎、股骨颈和桡骨远端的终末标本中，相对于OVX猴，松质骨体积显著增加。在所有部位，PTH显著改善了骨小梁结构，表现为骨小梁数量增加（Tb. N）和骨小梁间隔减少（Tb，Sp），而骨小梁厚度无显著变化（Tb. Th）。这些结构变化的机制是通过在髂嵴和椎骨中观察到的小梁隧道的定性观察来提出的。假设增厚的单个骨小梁的纵向隧穿将其转化为多个骨小梁，导致Tb. Th正常化，但Tb. N增加。在髂嵴、椎骨和股骨颈中，PTH治疗12个月后的3 - 6个月停药期后，对松质骨体积的显著积极影响仍然明显。相应的增加Tb. N和减少Tb，Sp也保持显着的PTH停药后，在这三个网站。与其他骨骼相比，桡骨远端对PTH治疗或停药相对不敏感。总之，甲状旁腺素治疗显著改善了松质骨的质量和结构，在轴向和approxular网站。(Bone 28：150 - 159; 2001）（C）2001，Elsevier Science Inc. All rights reserved.
A key feature of postmenopausal osteoporosis is the loss of trabecular bone mass and connectivity. The current study focuses on these parameters in the assessment of long-term (12 and 18 months) parathyroid hormone (PTH) therapy and its withdrawal(6 months) in the ovariectomized cynomolgus monkey (Macaca fascicularis), a well-characterized model for bone changes associated with postmenopausal osteoporosis. We used static and dynamic histomorphometric parameters to assess the amount and architecture of cancellous bone in four clinically important sites for osteoporotic fractures, including the lumbar vertebra, femoral neck, distal radius, and iliac crest. Recombinant human PTH(1-34) was administered daily to two groups for 18 months at 1.0 mug/kg per day (n = 19) and 5.0 mug/kg per day (n = 21), To study the effects of PTH withdrawal, two groups were administered PTH(1-34) daily for 12 months at 1.0 mug/kg per day (n = 20) and 5.0 mug/kg per day (n = 20), followed by daily administration of vehicle for 6 months. Sham-ovariectomized and ovariectomized (ovx) groups each received daily injections of vehicle for 18 months. Treatment with PTH had minimal effects on bone formation rates at the timepoints studied, but markedly increased cancellous bone volume relative to ovx monkeys in iliac crest biopsies at 6 and 15 months, as well as in terminal specimens of lumbar vertebrae, femoral neck, and distal radius after 18 months. At all sites, PTH significantly improved trabecular architecture, as evidenced by increased trabecular number (Tb.N) and decreased trabecular separation (Tb,Sp), with no significant change in trabecular thickness (Tb.Th). The mechanism of these structural changes is suggested by qualitative observations of trabecular tunneling observed in the iliac crest and vertebra. Longitudinal tunneling of thickened individual trabeculae is hypothesized to convert them into multiple trabeculae, resulting in a normalization of Tb.Th, but an increase in Tb.N. A significant positive effect on cancellous bone volume was still apparent after a 3-6 month withdrawal period following 12 months of PTH treatment in the iliac crest, vertebra, and femoral neck. Corresponding increases in Tb.N and decreases in Tb,Sp also remained significant after PTH withdrawal at these three sites. The distal radius was relatively insensitive to PTH treatment or its withdrawal, compared with the other bones. In summary, PTH therapy dramatically improved cancellous bone mass and architecture in both axial and appendicular sites. (Bone 28:150-159; 2001) (C) 2001 by Elsevier Science Inc. All rights reserved.