Effects of D-003, a mixture of high molecular weight aliphatic acids from sugar cane wax, on bones from ovariectomized rats.

Abstract

Bisphosphonates inhibit bone resorption through mechanisms involving the metabolic pathway from mevalonate to cholesterol. Mevalonate is a precursor of the lipoids required for osteoclast activity and thus inhibition of its synthesis affects bone metabolism. Inhibitors of hydroxymethylglutaryl CoA (HMGCoA) reductase might increase experimentally new bone formation through a mevalonate-dependent effect. D-003 is a mixture of high molecular weight fatty acids isolated from sugar cane wax, which inhibits cholesterol biosynthesis through indirect regulation of HMGCoA reductase activity. This study was undertaken to determine whether D-003 could prevent bone loss in ovariectomized rats. Sprague Dawley female rats were ovariectomized or sham operated and were randomly distributed into five groups: a control ovariectomized and a sham (false-operated) group receiving Tween/H2O vehicle, a group treated with alendronate (3 mg/kg/day) and two groups treated with D-003 (50 and 200 mg/kg/day). Treatments were administered for 3 months. At sacrifice, bones were removed and histological variables of bone resorption and formation were studied by histomorphometry. Ovariectomy diminished trabecular number and thickness and increased trabecular gap, osteoclast number and surface. Alendronate and D-003 prevented a decrease in trabecular number and thickness as well as increases in trabecular separation, osteoclast number and surface compared with ovariectomized controls, thus preventing the bone loss and decreased bone resorption induced by ovariectomy, but failed to increase osteoblast surface compared with control ovariectomized rats. In conclusion, D-003 (50 and 200 mg/kg/day) prevented bone loss and decreased bone resorption in ovariectomized rats, which suggests that this substance could be promising in preventing or treating osteoporosis.