Femoral head blood flow reduction and hypercoagulability under 24 h megadose steroid treatment in pigs

Abstract

The pathogenesis of corticosteroid-induced femoral head necrosis is assumed to be ischemia. The purpose of this study was to investigate the perfusion pattern of the femoral head and plasma coagulability during 24 h corticosteroid megadose treatment, as recommended by the National Acute Spinal Cord Injury Studies (NASCIS), in the awake big animal model. Blindedly, 9 animals underwent megadose methylprednisolone infusion (30 mg/kg intravenously as a n initial bolus, followed by 5.4 mglkglh for further 23 h) while 9 animals served as placebo treated controls. Regional blood flow of the systematically subdivided femoral head, proximal femur, acetabulum, and soft tissue hip regions was investigated by the microsphere technique at steady state (phase I), after the initial bolus infusion (phase 2), and after the completed treatment (phase 3). Plasma coagulability was examined in phases 1 and 3. Blood flow of the femoral head epiphysis and metaphyseal cancellous bone was unchanged after one hour of steroid infusion, but decreased after the completed treatment at 24 h in the experimental group. Femoral head blood flow reduction was global without a tendency to more pronounced blood flow decrease in any subregion. Plasma fibrinogen was significantly higher after 24 h of steroid infusion than in the placebo control group. 24 h high dose methylprednisolone treatment causes femoral head blood flow reduction and hypercoagulability of plasma in the normal awake immature pig. These findings may be pathogenetic factors in the early stage of steroid-induced osteonecrosis.

Biomarkers and pharmaceutical strategies in steroid-induced osteonecrosis of the femoral head: A literature review

“…These theories include vascular occlusion or ischaemia, altered fat metabolism, fat emboli and intravascular coagulation. 1,[3][4][5][6][7][8][9] Biomarkers Lipoprotein. Patients with ONFH were found to have lower serum apolipoprotein A-IV concentrations compared with healthy volunteers, and these concentrations increased with stage of disease.…”

Osteonecrosis of the femoral head: An update in year 2012

“…Cryogenic and thermal insults have been used to induce osteonecrosis in quadrupeds such as canines [60] and bipeds such as emus [61] . Intramuscular injection of methylprednisolone has been used to develop steroid-induced osteonecrosis in mouse [62] , rat [63] , rabbit [64,65] , pig [66] , and chicken models [18] , where the percent incidence of induced osteonecrosis is dependent on the amount of methylprednisolone injected. These animal models have been used to study the molecular mechanisms of osteonecrosis and assess the usefulness of several therapies over the last few decades.…”

Vasculature deprivation – induced osteonecrosis of the rat femoral head as a model for therapeutic trials

“…Glucocorticoid-promoted expression of the RANK-ligand by the osteoblasts represents a central pathway in osteoclast maturation [123]. The activation of the RANK-ligand is linked to the injured bony matrix, increased permeability of the matrix, and fragmentation of osteoblast and osteocyte DNA.…”