Inducible osteonecrosis in a rabbit serum sickness model: deposition of immune complexes in bone marrow

We established inducible osteonecrosis in a rabbit serum sickness model. Osteonecrosis with marrow necrosis could be induced by the intravenous injection of horse serum in two doses separated in time by a period of three weeks. In this model, osteonecrosis could be successfully produced in rabbit femoral metaphysis. The incidence of marrow necrosis was 45% (9 of 20 rabbits) and trabecular necrosis occurred in 6 of 20 rabbits (30%) at 7 days after the second injection of the horse serum. In bone marrow of the femoral metaphysis, extravasation of erythrocytes and the formation of micro-thrombi in arterioles were often observed in an early stage of the present model and both findings correlate well each other (p = 0.0001). Immune complexes could be demonstrated using immunohistochemistry in bone marrow of the femoral metaphysis as well as in glomeruli of the kidney. Extravasation of erythrocytes in bone marrow of the femoral metaphysis was observed in 8 of 12 (67%) cases with immune complex deposition in the sinusoidal space of the femoral metaphysis and in 12 of 21 (57%) cases with immune complex deposition in glomeruli of the kidney. Immune complex deposition both in the sinusoidal space of femoral bone marrow (p = 0.0385) and in glomeruli of the kidney (p = 0.0209) closely related to extravasation of erythrocytes and microthrombi in arterioles in the early stage of this model. Early microcirculatory injury (extravasation of erythrocytes and microthrombi in arterioles) adjacent to osteonecrosis could be induced by immune complex deposition in femoral bone marrow and might be predictable characteristics for the inducible osteonecrosis in the present serum sickness model. The important findings in this study were that early microcirculatory injury was closely related to the deposition of immune complexes in femoral bone marrow, and that early microcirculatory injury associated with immune complex deposition was located close to osteonecrotic regions.