Monitoring of intermittent PTH(1-34) treatment by serum PINP in adult ovariectomized osteopenic rats

Jussi Halleen, ZhiQi Peng, Katja Fagerlund, Tiina A. Suutari, Jukka Vääräniemi, Mari Suominen, Jukka Rissanen, Harrie C.M. Boonen, Trine S.R. Neerup, Hanne H. Bak, Jussi M Halleen

    Publikation: KonferencebidragPosterForskning

    Abstract

    Procollagen I N-terminal propeptide (PINP) is a sensitive marker of bone formation for monitoring the efficacy of treatment with recombinant human parathyroid hormone (1-34) analog [PTH(1-34)] in osteoporotic patients. Recently, a new immunoassay has been developed for serum PINP in rodents, allowing measurement of serum PINP in preclinical rodent osteoporosis models. The purpose of this study was to evaluate the use of serum PINP for monitoring intermittent PTH(1-34) treatment in adult ovariectomized (OVX) osteopenic rats. Study groups included a sham-operated control group and an OVX-operated control group receiving vehicle, and OVX-operated groups receiving daily subcutaneous injections of 1.2, 4.0, 12.0, 40.0 and 120.0 µg/kg human PTH(1-34). Each group contained 12 animals that were 6 months of age at the time of the operations. Dosing was started at 7 weeks after OVX and continued for 6 weeks. Before the start of treatment, the animals were randomized to groups based on their body weights and trabecular bone mineral density values obtained by peripheral quantitative computed tomography (pQCT). PINP values were determined from serum samples collected before the start of treatment, at 2 weeks after the start of treatment and at the end of the study. The PINP values obtained at 2 weeks and at the end of the study were divided by the values obtained in the same animal before the start of treatment to determine the change of PINP in each animal during the treatment. PTH(1-34) treatment showed strong anabolic effects in tibial metaphysis, tibial diaphysis and vertebra based on bone parameters determined by pQCT measurements and static and dynamic histomorphometry. Serum PINP values showed a strong dose-dependent increase by PTH(1-34) treatment both at 2 weeks after start of treatment and at the end of the study. We conclude that serum PINP is a reliable marker for monitoring the effects of anabolic treatment with PTH(1-34) in the rat OVX model, and short-term changes in serum PINP values predict long-term changes in bone parameters obtained by pQCT measurements and histomorphometry.
    OriginalsprogEngelsk
    Publikationsdato16 okt. 2010
    Antal sider1
    StatusUdgivet - 16 okt. 2010
    BegivenhedASBMR 2010 Annual Meeting - Toronto, Canada
    Varighed: 15 okt. 201019 okt. 2010

    Konference

    KonferenceASBMR 2010 Annual Meeting
    Land/OmrådeCanada
    ByToronto
    Periode15/10/201019/10/2010

    Bibliografisk note

    J Bone Miner Res 25 (Suppl 1)

    Citationsformater