The effect of a proton pump inhibitor on bone metabolism in ovariectomized rats

Moon Kyung Joo, Jong Jae Park, Beom Jae Lee, Ji Hoon Kim, Jong Eun Yeon, Jae Seon Kim, Kwan Soo Byun, Young Tae Bak

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    15 Citations (Scopus)

    Abstract

    Recent studies revealed that long-term intake of proton pump inhibitor (PPI) increases the risk of vertebral or hip fracture; however, the exact mechanism for this is not known. To evaluate the effect of long-term PPI therapy on bone turnover, we analyzed the signaling pathway involved in osteoclast differentiation and bone resorption/formation markers using ovariectomized rats. Six-week-old Sprague-Dawley (S-D) rats were ovariectomized, and two weeks later they were divided into four groups (group A, normal diet + placebo; group B, low calcium diet + placebo; group C, normal diet + PPI; and group D, low calcium diet + PPI). Omeprazole, at a concentration of 30 mg/kg, was administered orally for eight weeks and the rats were sacrificed when they were 16 weeks old. The relative expression levels of the receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) ratio, c-Fos, nuclear factor of activated T cells c1 (NFATc1) and osteocalcin in femoral bone marrow cells were compared, and serum C-terminal crosslinking telopeptide of type I (CTX-1) levels were determined. The relative ratio of RANKL/OPG was increased in group D, and gene expression levels of c-Fos and NFATc1 were upregulated in groups B and D, which are involved in differentiation and activation of osteoclasts. Furthermore, expression levels of osteocalcin, a bone formation marker, were decreased and levels of serum CTX-1, a bone resorption marker, were increased in group D. Taken together, a low calcium diet and PPI administration are thought to collaborate in order to alter osteoclast activity and bone resorption signaling.

    Original languageEnglish
    Pages (from-to)1267-1272
    Number of pages6
    JournalMolecular Medicine Reports
    Volume7
    Issue number4
    DOIs
    Publication statusPublished - 2013 Apr

    Keywords

    • Bone metabolism
    • Osteoclast
    • Proton pump inhibitor

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Medicine
    • Molecular Biology
    • Genetics
    • Oncology
    • Cancer Research

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