Comparison of the effects of D-003, a mixture of high-molecular-weight aliphatic acids from sugarcane wax, and pravastatin on bones and osteoclast apoptosis of ovariectomized rats.

Abstract

The mevalonate pathway is relevant in bone cells. Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the key enzyme of this route, stimulating osteoblast differentiation and activity. Pravastatin increases bone formation markers in postmenopausal women and bone density in diabetics. D-003 is a mixture of high-molecular-weight acids purified from sugarcane wax which inhibits cholesterol biosynthesis through HMG-CoA reductase regulation, preventing bone loss in osteoporosis induced with ovariectomy and prednisolone in rats. We investigated the effects of D-003 (50 mg/kg) and pravastatin (20 mg/kg) orally administered for 12 weeks to ovariectomized rats. Female rats were randomized in four groups (10 rats/group): two control groups treated with the vehicle, one false-operated (sham) and another ovariectomized (positive control), while two other groups received D-003 or pravastatin. Bone resorption and formation was studied through histomorphometry and apoptosis through immunohistochemistry. D-003 and pravastatin significantly (p < 0.001) prevented the changes of trabecular bone versus ovariectomized rats and (p < 0.001) the increase of the surface and number of osteoclasts versus ovariectomized controls. D-003 and pravastatin, however, did not modify osteoblast surfaces, a bone formation marker D-003 and pravastatin increased osteoclast apoptosis and reduced (p < 0.05) osteoblast and osteocyte apoptosis versus ovariectomized controls; D-003 was more effective (p < 0.05) than pravastatin. In conclusion, D-003 (50 mg/kg) orally administered for 12 weeks prevented bone loss and bone resorption in ovariectomized rats, increasing osteoclast apoptosis. The preventive effects of D-003 on bone loss and resorption in ovariectomized rats are comparable to those of pravastatin. Both drugs inhibited osteoblast apoptosis but failed to change osteoblast surface. The effects of D-003 on bone cell apoptosis were greater than those of pravastatin. Therefore, D-003 could be used to prevent or treat bone loss in postmenopausal women, but further animal studies and clinical trials are required to confirm the clinical relevance of this potential effect.