Pravastatin reduces steroid-induced osteonecrosis of the femoral head in SHRSP rats.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Our data suggest that pravastatin may be effective in reducing steroid-induced ONFH.
Department of Orthopedic Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan.
Yoshihiro
Y
Nozaki
Kenji
K
Kumagai
Noriaki
N
Miyata
Masami
M
Niwa
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D060766:Drinking Water; D005271:Femur Head Necrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077555:Methylprednisolone Acetate; D018384:Oxidative Stress; D017035:Pravastatin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR
D000893:Anti-Inflammatory Agents; D060766:Drinking Water; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000077555:Methylprednisolone Acetate; D017035:Pravastatin; D008775:Methylprednisolone