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Effect of simvastatin on steroid-induced osteonecrosis evidenced by the serum lipid level and hepatic cytochrome P4503A in a rabbit model

  • Original Article
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Journal of Orthopaedic Science

Abstract

Objective

This study was designed to investigate the efficacy of lipid-lowering agents in preventing steroid-induced osteonecrosis and the mechanism by which they do so in a rabbit model.

Methods

Female Japanese white rabbits were randomly allocated to receive probucol (group P), pravastatin (group PS), simvastatin (group SS), or saline (group C) for 6 weeks (n = 15 in groups P, PS, and SS; n = 30 in group C). Methylprednisolone (20 mg/kg) was injected at 3 weeks after starting treatment, and the femurs were histologically examined bilaterally 3 weeks after methylprednisolone injection. Midazolam clearance was measured before treatment and before methylprednisolone injection to determine hepatic cytochrome P4503A (CYP3A) levels.

Results

The incidence of osteonecrosis in the proximal metaphysis of the femurs in groups PS and SS was significantly lower than in group C (P < 0.05 and P < 0.0001, respectively), whereas it did not differ between groups P and C. It was significantly lower in group SS than in group PS (P < 0.05). Plasma concentrations of lipids (low-density lipoprotein, triglyceride, free fatty acid, and total cholesterol) in groups P, PS, and SS were significantly lower than in group C; and hepatic CYP3A levels were significantly higher in group SS than in groups P or PS after treatment (P < 0.005 for both).

Conclusions

Simvastatin and pravastatin significantly reduced the incidence of steroid-induced osteonecrosis in rabbits. Simvastatin was more effective in reducing the incidence of the disease, and increased CYP3A activity is a possible mechanism for this effect.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan

    Kentaro Iwakiri, Yasunori Kaneshiro, Hiroyoshi Iwaki, Toshiaki Masada, Akio Kobayashi & Kunio Takaoka

  2. Department of Anesthesiology and Intensive Care Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan

    Yutaka Oda & Akira Asada

Authors
  1. Kentaro Iwakiri
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  2. Yutaka Oda
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  3. Yasunori Kaneshiro
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  4. Hiroyoshi Iwaki
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  5. Toshiaki Masada
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  6. Akio Kobayashi
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  7. Akira Asada
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  8. Kunio Takaoka
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Iwakiri, K., Oda, Y., Kaneshiro, Y. et al. Effect of simvastatin on steroid-induced osteonecrosis evidenced by the serum lipid level and hepatic cytochrome P4503A in a rabbit model. J Orthop Sci 13, 463–468 (2008). https://doi.org/10.1007/s00776-008-1257-z

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  • DOI: https://doi.org/10.1007/s00776-008-1257-z

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