Effects of D-003 (5-200 mg/kg), a mixture of high molecular weight aliphatic acids from sugarcane wax, on bones and bone cell apoptosis in ovariectomized rats.

Abstract

The mevalonate pathway is crucial for osteoclast function. D-003 is a mixture of high molecular weight acids purified from sugarcane wax, which inhibits cholesterol biosynthesis through HMG-CoA reductase regulation. D-003 administered at 50 and 200 mg/kg for 12 weeks prevented bone loss in ovariectomized rats, increasing osteoclast apoptosis. The present study investigated whether the effects of D-003 on bone resorption and osteoclast apoptosis are dose-dependent. Rats were randomized into seven groups (10 rats/group): two control groups orally treated with the vehicle, one false-operated (sham) and another ovariectomized group (positive control), while another four groups received D-003 (5, 25, 50 and 200 mg/kg). The effects on bone resorption and formation were studied through histomorphometry and the effects on apoptosis through immunohistochemistry. D-003 (5-200 mg/kg) dose-dependently and significantly prevented (p < 0.001) changes in trabecular bone and increase in osteoclast surface and number versus ovariectomized controls, leaving osteoblast surfaces unchanged. Across the dose range, D-003 significantly increased (p < 0.05) osteoclast apoptosis in a dose-dependent manner and reduced (p < 0.05) osteoblast and osteocyte apoptosis versus ovariectomized controls, but these effects did not show dose dependence. In conclusion, D-003 (5-200 mg/kg) orally administered at for 12 weeks prevented bone loss and bone resorption and increased osteoclast apoptosis in ovariectomized rats in a dose-dependent manner. These results are consistent with previous data, showing that D-003 administered at relatively low doses prevents bone loss induced with ovariectomy, which could be useful to prevent or treat bone loss in postmenopausal women. Further experimental and clinical studies, however, are needed to confirm these findings.