Prevention of corticosteroid-induced osteonecrosis in rabbits by intra-bone marrow injection of autologous bone marrow cells

Objectives. Femoral head osteonecrosis (ON) is a serious complicationof steroid administration. We evaluated bone marrow transplantation(BMT) for preventing corticosteroid-induced ON. Methods. Rabbits, injected with methylprednisolone (MPSL; 20mg/kg), were divided into four groups: (i) MPSL alone; MPSLinjection only, (ii) MPSL+needling; 2 days after MPSL injection,a hole (1.2 mm diameter) was drilled from the outer cortex 2.5cm distal to the proximal end of the greater trochanter, (iii)MPSL+saline; 2 days after MPSL injection, 2 ml saline was injecteddirectly into the bone marrow cavity, and (iv) MPSL+BMT; 2 daysafter MPSL injection, 1 x 10⁷/2 ml bone marrow cells (BMCs)were injected directly into the bone marrow cavity. Platelets,fibrinogen, prothrombin time and total cholesterol in peripheralblood were measured before and after treatment. Tissues werestained with haematoxylin and eosion and terminal deoxynucleotidyl-mediateddeoxyuridine triphosphate nick-end labelling stain and immunostainedfor VEGF, while cell proliferation and viability of whole BMCsin the femur were analysed by cell cycle analysis and [³H]-thymidineuptake. Results. The ON incidence in rabbits treated with MPSL alone,MPSL+needling and MPSL+saline was 72.7, 70.0 and 66.7%, respectively,while in the MPSL+BMT group, the incidence was 0%. Serologicalfindings in the MPSL+BMT group were almost normalized. VEGFand TUNEL staining were reduced in the MPSL+BMT group comparedwith all other groups. There were significantly fewer BMCs inG1 phase from the MPSL+BMT group than the other groups, whileuptake of [³H]-thymidine was significantly increased. Conclusion. Direct injection of autologous BMCs into femursprevents corticosteroid-induced ON following treatment withhigh-dose, short-term steroids. KEY WORDS: Corticosteroid, Osteonecrosis, Animal model, Bone marrow transplantation, Bone marrow cellsSubmitted 10 June 2007; revised version accepted 15 January 2008.