Effect of D-003, a mixture of high molecular weight aliphatic acids, on glucocorticoid- and lipopolysaccharides [LPS]-induced osteonecrosis

ABSTRACT

Osteonecrosis [ON] is characterized through the impairment of osseous blood flow that leads to the collapse of femur head. Corticoid-induced ON in rats and lipopolysaccharide [LPS]-induced in rabbits are useful models to assess the efficacy of potential treatments on this disease. D-003 inhibits the mevalonate pathway, lipid peroxidation and prevents osteoporosis in rats through increasing the osteoclast apoptosis. This study investigated the effects of D-003 on corticoid- and LPS-induced ON in rats and rabbits. Corticoid-induced ON Rats were randomized into five groups. A negative control and four groups treated with prednisolone 6 mg/Kg a positive control and three treated with D-003 [5, 25 and 200 mg/Kg] for 80 days. All positive controls presented ON areas. D-003 significantly reduced the numbers and proportions of ON lesions, as compared to the positive control group. LPS-induced ON in rabbits Rabbits were randomized into five groups a negative control and four injected with a single intra-venous injection of LPS [10 micro g/Kg] including a positive control and three with D-003 [5, 25 and 200 mg/Kg] for 30 days. ON was seen in all positive controls. The incidence of ON and the number of ON lesions in the groups treated with D-003 [25 and 200 mg/Kg] was significantly lower compared to the positive controls. LPS injection significantly increased the size of bone marrow fat cells in positive controls and such increase was significantly decreased by D-003. In conclusion, D-003 reduced ON lesions in corticoid-and LPS-induced ON and also the size of bone marrow fat cells in rabbits with LPS