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.
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.
Authors: Nobuhiro Kamiya; Ryosuke Yamaguchi; Olumide Aruwajoye; Naga Suresh Adapala; Harry K W Kim Journal: Clin Orthop Relat Res Date: 2015-02-10 Impact factor: 4.176
Authors: Cecilia Sheen; Tiffaney Vincent; David Barrett; Edwin M Horwitz; Jessica Hulitt; Eliza Strong; Stephan A Grupp; David T Teachey Journal: Br J Haematol Date: 2011-05-09 Impact factor: 6.998