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Short-Term Changes in Serum PINP Predict Long-Term Changes in Trabecular Bone in the Rat Ovariectomy Model

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Abstract

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 17β-estradiol (E2, 10 μg/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. E2 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.

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Abbreviations

BMD:

bone mineral density

CTX:

C-terminal cross-linked telopeptides of type I collagen

OVX:

ovariectomy

PINP:

serum procollagen I N-terminal propeptide

pQCT:

peripheral quantitative computed tomography

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Acknowledgments

The authors thank Ms. Maria Kapraali from Oulu University of Applied Sciences for her skillful technical assistance.

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Authors and Affiliations

  1. Pharmatest Services, Itäinen Pitkäkatu 4 C, 20520, Turku, Finland

    Jukka P. Rissanen, Mari I. Suominen, Zhiqi Peng, Jukka Morko & Jussi M. Halleen

  2. Suomen Bioanalytiikka Ltd (SBA), Professorintie 5, Oulu, 90220, Finland

    Simo Rasi

  3. Department of Clinical Chemistry, University of Oulu, Kajaanintie 50, Oulun yliopisto, Oulu, 90014, Finland

    Juha Risteli

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  1. Jukka P. Rissanen
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  2. Mari I. Suominen
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  3. Zhiqi Peng
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  4. Jukka Morko
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  5. Simo Rasi
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  7. Jussi M. Halleen
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Correspondence to Jussi M. Halleen.

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Rissanen, J.P., Suominen, M.I., Peng, Z. et al. Short-Term Changes in Serum PINP Predict Long-Term Changes in Trabecular Bone in the Rat Ovariectomy Model. Calcif Tissue Int 82, 155–161 (2008). https://doi.org/10.1007/s00223-007-9101-6

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  • DOI: https://doi.org/10.1007/s00223-007-9101-6

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