Effects of D-003 on Lipopolysaccharides-induced Osteonecrosis in Rabbits

D-003, a mixture of high molecular weight acids, inhibits cholesterol synthesis prior to mevalonate and prevents osteoporosis induced by ovariectomy in rats, and both osteoporosis and osteonecrosis induced by corticoids in rats. The aim of this study was to investigate effects of D-003 on lipopolysaccharides-induced osteonecrosis in rabbits. Animals were randomized into 5 groups: a sham and four groups injected with lipopolysaccharides: one treated orally with vehicle and three with D-003 (5, 25 and 200 mg/kg, respectively) during four weeks. We assessed the effects of treatments on the incidence of osteonecrosis (number of animals with osteonecrosis lesions/animals per group), the mean numbers and areas of osteonecrosis per animal and on the mean sizes of the bone marrow fat cells. The incidence of osteonecrosis in the groups of D-003 25 and 200 mg/kg was significantly lower than in the positive controls. The reduction of osteonecrosis increased with the doses, but significant dose-dependence relationship was not achieved. D-003 significantly and dose-dependently decreased the number of osteonecrosis lesions per animal as compared to the positive controls. Likewise, the mean osteonecrosis areas in the proximal femoral and humeral bones were significantly decreased by D-003. The injection of lipopolysaccharides significantly increased the average size of bone marrow fat cells as compared to the negative controls, and such increase was significantly and markedly reduced with D-003. It is concluded that D-003 reduced the incidence, number and percent areas of osteonecrosis lesions, and the size of bone marrow fat cells, a marker of adipogenesis, in rabbits with lipopolysaccharides-induced ostenonecrosis.