Date Published: February 8, 2012
Publisher: Informa Healthcare
Author(s): Yoshihiro Nozaki, Kenji Kumagai, Noriaki Miyata, Masami Niwa.
Although the definite cause of steroid-induced osteonecrosis of the femoral head (ONFH) is unknown, peripheral circulatory failure, lipid metabolism disturbance, and increased oxidative stress are considered to be possible causes. We investigated whether pravastatin as a statin treatment reduces (1) the incidence of ONFH, (2) the adipocyte area, and (3) bone marrow changes in the femoral head.
We divided up 81 thirteen-week-old spontaneously hypertensive stroke-prone (SHRSP)/Izm male rats into 4 groups: a control group (group C), a group given pravastatin (group P), a group given steroid (group S), and a group given both pravastatin and steroid (Group PS). The steroid was administered at 15 weeks of age. Pravastatin, as a statin, was administered in the drinking water for 4 weeks. The rats were killed when 17 weeks old. Osteonecrosis was diagnosed based on histopathological examination. Oxidative stress was assessed from immunostaining.
The incidence of histological osteonecrosis was lower in the groups given pravastatin. The percentage of adipocyte area in the bone marrow was lower in the PS group than in the S group. Immunohistochemical staining for oxidative stress showed that staining was less in the PS group than in the S group. Pravastatin had no effect on the blood-derived biochemical findings on lipid metabolism. However, it reduced the incidence of steroid-induced ONFH in these SHRSP rats. We presume that this occurred by reducing oxidative stress and by reducing the percentage of adipocyte area in the femoral heads.
Our data suggest that pravastatin may be effective in reducing steroid-induced ONFH.
Circulatory disturbance, impairment of lipid metabolism, and increased oxidative stress have been suggested to be involved in the etiology of steroid-induced ONFH. Many drugs to inhibit these have been tested in animals and humans, resulting in reports of prevention or suppression of the progression of ONFH by the administration of warfarin, low-molecular-weight heparin, statins, and vitamin E (Pritchett 2001, Glueck et al. 2005, Mont et al. 2006, Nagasawa et al. 2006, Kuribayashi et al. 2010). Glueck et al. (2005) studied 224 patients: 26 patients with multifocal osteonecrosis, 91 patients with unifocal osteonecrosis, and 117 control patients. They found that osteonecrosis was associated with familial thrombophilia and eNOS T-786C polymorphism.