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Effect of Raloxifene on Arthritis and Bone Mineral Density in Rats with Collagen-Induced Arthritis

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Abstract

We studied the effect of raloxifene (RAL) on arthritis and bone mineral density (BMD) in rats with collagen-induced arthritis (CIA). Seven-month-old female Sprague–Dawley rats were divided into five groups: rats without CIA (CNT), CIA rats that underwent ovariectomy (OVX) and were treated with RAL (CIA + OVX + RAL), CIA rats that underwent OVX and were treated with vehicle (CIA + OVX + Veh), CIA rats that had sham surgery and were treated with RAL (CIA + sham + RAL), and CIA rats that had sham surgery and were treated with vehicle (CIA + sham + Veh). RAL was orally administered at 10 mg/kg every day for 3 weeks, beginning 1 week after initial sensitization until death at 4 weeks. Every week until death, we evaluated hind paw thickness and arthritis score. BMD was measured by peripheral quantitative computed tomography at the distal metaphysis and the diaphysis of the femur; we also performed histomorphometry of the proximal tibia and histological evaluation of arthritis. RAL administration suppressed hind paw thickness and arthritis score and prevented decreases in BMD and cortical thickness. In the histomorphometric analysis, bone-resorption parameters were significantly lower in the RAL groups than in the Veh groups. RAL significantly inhibited synovial proliferation in CIA rats. RAL effects on arthritis and bone were apparent regardless of whether an animal had undergone OVX. RAL could suppress arthritis and bone loss in estrogen-replete or -depleted rats. These findings, using an animal model, indicate the potential usefulness of RAL as an effective treatment for premenopausal RA patients as well as postmenopausal ones.

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Acknowledgements

Lilly Research Laboratories supplied the RAL, and we acknowledge their support. We also acknowledge Kiichi Nonaka for advice on peripheral QCT analysis and Akemi Ito for assistance in preparing and staining tissue sections.

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Faculty of Medicine, Tottori University, Yonago, Japan

    Ikuta Hayashi, Toru Okano, Makoto Enokida & Ryota Teshima

  2. School of Health Science and Rehabilitation Division, Faculty of Medicine, Tottori University, Yonago, Japan

    Hiroshi Hagino

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  1. Ikuta Hayashi
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  2. Hiroshi Hagino
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  3. Toru Okano
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  4. Makoto Enokida
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  5. Ryota Teshima
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Correspondence to Ikuta Hayashi.

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The authors have stated that they have no conflict of interest.

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Hayashi, I., Hagino, H., Okano, T. et al. Effect of Raloxifene on Arthritis and Bone Mineral Density in Rats with Collagen-Induced Arthritis. Calcif Tissue Int 88, 87–95 (2011). https://doi.org/10.1007/s00223-010-9432-6

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  • DOI: https://doi.org/10.1007/s00223-010-9432-6

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