Short-term changes in serum PINP predict long-term changes in trabecular bone in the rat ovariectomy model

Short-term changes in serum PINP predict long-term changes in trabecular bone in the rat ovariectomy model
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DOI:
10.1007/s00223-007-9101-6
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发表时间:
2008-02-01
影响因子:
4.2
通讯作者:
Halleen, Jussi M.
Halleen, Jussi M.
中科院分区:
医学3区
文献类型:
--
作者:
Rissanen, Jukka P.;Suominen, Mari I.;Halleen, Jussi M.

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血清前胶原I N-末端前肽(PINP)是人类骨形成的敏感标志物。我们建立了大鼠PINP的非放射性免疫测定方法,并在大鼠卵巢切除(OVX)模型中研究了PINP作为骨形成标志物的作用。对3月龄大鼠进行了两项OVX研究,均包括测量PINP、I型胶原C端交联端肽(CTX)和骨钙素N端中段。一项为期14天的初步研究包括假手术对照组和OVX组,一项为期8周的广泛研究包括假手术对照组和接受溶媒和17 β-雌二醇(E-2,10 μ g/kg/天s.c.)的OVX组。在初步研究中,在手术前和第2、4、7、10和14天测量骨标志物,在广泛研究中,在手术前和第2和8周测量骨标志物。在广泛的研究中,通过外周定量计算机断层扫描和胫骨干骺端的组织形态计量学测定了骨小梁参数。大鼠PINP免疫分析具有以下特征:批内变异系数(CV)为2.8%,批间CV为7.5%,稀释线性为95%,回收率为107%。PINP在OVX后的前2周内显著增加,并在8周时恢复到假手术水平。E-2可阻止OVX引起的增加。2周时PINP的变化与2周时CTX和骨钙素的变化以及8周时骨小梁参数的变化密切相关。总之,PINP的短期变化预测骨小梁参数的长期变化,表明PINP是大鼠OVX模型中骨形成的可靠标志物。
Serum procollagen I N-terminal propeptide (PINP) is a sensitive bone formation marker in humans. We have developed a nonradioactive immunoassay for rat PINP and studied PINP as a bone formation marker in the rat ovariectomy (OVX) model. Two OVX studies were performed with 3-month-old rats, both including measurement of PINP, C-terminal cross-linked telopeptide of type I collagen (CTX), and N-terminal mid-fragment of osteocalcin. A pilot 14-day study contained a sham-operated control group and an OVX group, and an extensive 8-week study contained a sham-operated control group and OVX groups receiving vehicle and 17 beta-estradiol (E-2, 10 mu g/kg/day s.c.). The bone markers were measured before the operation and at days 2, 4, 7, 10, and 14 in the pilot study and before the operations and at 2 and 8 weeks in the extensive study. Trabecular bone parameters were determined by peripheral quantitative computed tomography and histomorphometry from tibial metaphysis in the extensive study. The rat PINP immunoassay had the following characteristics: intra-assay coefficient of variation (CV) 2.8%, interassay CV 7.5%, dilution linearity 95%, and recovery 107%. PINP increased significantly during the first 2 weeks after OVX and returned to sham level at 8 weeks. E-2 prevented the increase caused by OVX. Changes in PINP at 2 weeks correlated strongly with changes in CTX and osteocalcin at 2 weeks and with trabecular bone parameters at 8 weeks. As a conclusion, short-term changes in PINP predict long-term changes in trabecular bone parameters, suggesting that PINP is a reliable marker of bone formation in the rat OVX model.