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

Abstract

Background and purpose 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.Interpretation Our data suggest that pravastatin may be effective in reducing steroid-induced ONFH.

Steroid-induced osteonecrosis of the femoral head reveals enhanced reactive oxygen species and hyperactive osteoclasts

“…Firstly, an anti-ROS group was not included in this study. It was previously indicated that anti-oxidative stress treatments indeed prevent or alleviate steroid-induced ONFH by affecting blood vessel, osteocytes, and adipose tissues [35,36,[48][49][50], but with the lack of data on the role of osteoclasts. Osteoclast acts as a major contributor to the collapse of femoral head and the agents like bisphosphonates were also shown to have beneficial effects on ONFH [13].…”

Epidermal growth factor (EGF) promotes bone healing in surgically induced osteonecrosis of the femoral head (ONFH)

“…Nevertheless, a decreased vascular supply to the subchondral bone of the femoral head has been recognized as the underlying cause of osteocyte death in ONFH. The treatment may include surgical (CD, bone grafting, osteotomy, arthroplasty) and/or pharmaceutical (bisphosphonates, iloprost, statins) approach [12,[14][15][16]. CD was first described by Hopson and Siverhus in 1988 [12], and since then, it has been commonly used in the treatment of early-stage ONFH (stage 1-2).…”

Pleiotropic effects of statins on the treatment of chronic periodontitis – a systematic review

“…It has been shown that statins are able to reduce the incidence of steroid‐induced osteonecrosis . The better, yet not completely, understood mechanism by which statins affect osteonecrosis might help to explain its effects on PD.…”