title: The effect of D-003 (10 mg/day) on biochemical parameters of bone remodelling in postmenopausal women: a randomized, double-blind study.
abstract: Biphosphonates, which are antiresorptive agents used to treat osteoporosis, inhibit the mevalonate pathway, preventing protein prenylation and inhibiting osteoclast activity. Statins decrease cholesterol biosynthesis by blocking the mevalonate pathway and have been reported to have beneficial effects on bone. D-003 is a mixture of high molecular weight acids purified from sugarcane wax that inhibits cholesterol biosynthesis before mevalonate production. D-003 prevents bone loss and resorption in rats with osteoporosis induced with ovariectomy or corticoids. Biochemical markers of bone turnover are used to monitor the short-term efficacy of antiosteoporotic therapy. This randomized, double-blind, placebo-controlled study was undertaken to investigate the short-term effects of D-003 (10 mg/day) on biochemical markers of bone turnover in postmenopausal women with low bone mineral density (BMD). After 4 weeks on a low-fat diet, 34 women were randomized to D-003 (10 mg/day) or placebo for 6 months. Pre- and post-treatment samples were analyzed for urinary excretion of deoxypyridinoline (DPD)/creatinine (Cr), a marker of bone resorption, and serum bone specific alkaline phosphatase (BSAP), a marker of bone formation. The effects on lipid profile and safety indicators, as well as adverse events (AE), were investigated. D-003 (10 mg/day) lowered urinary excretion of tDPD/Cr versus baseline (20.6%) (p < 0.001) and placebo (33.7%) (p < 0.01), but did not modify serum BSAP. D-003 decreased low-density lipoprotein-cholesterol (LDL-C) (32.8%), total cholesterol (TC) (16.4%) and the TC/high-density lipoprotein-cholesterol (HDL-C) ratio (34.7%), increased HDL-C (30.3%) (p < 0.001) and did not modify triglycerides. The effects on these variables were significant as early as 3 months after treatment initiation. D-003 was well tolerated. Three patients (one in the placebo group and two in the D-003 group) withdrew from the study. Two of these withdrawals were due to AE: abdominal pain (placebo) and heartburn (D-003). Five patients (four in the placebo group [22.2%] and one in the D-003 group [6.3%]) reported mild AE. In conclusion, D-003 (10 mg/day) reduced urinary excretion of tDPD/Cr, a bone resorption marker and did not change serum BSAP, a bone formation marker, while it lowered cholesterol in study patients. These preliminary results suggest that D-003 could be useful in treating postmenopausal women with low BMD. However, the potential value of D-003 in treating or preventing osteoporosis deserves further clinical investigation.
authors.affiliation: Medical-Surgical Research Center, Havana City, Cuba.
authors.forename: A
authors.initials: A
authors.lastname: Ceballos
authors.forename: R
authors.initials: R
authors.lastname: Mas
authors.forename: G
authors.initials: G
authors.lastname: Castaño
authors.forename: L
authors.initials: L
authors.lastname: Fernández
authors.forename: S
authors.initials: S
authors.lastname: Mendoza
authors.forename: R
authors.initials: R
authors.lastname: Menéndez
authors.forename: J J
authors.initials: JJ
authors.lastname: González
authors.forename: J
authors.initials: J
authors.lastname: Illnait
authors.forename: R
authors.initials: R
authors.lastname: Gámez
authors.forename: M
authors.initials: M
authors.lastname: Mesa
authors.forename: J
authors.initials: J
authors.lastname: Fernández
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine*; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000652:urine; D015519:Bone Density; D001862:Bone Resorption / Q000188:drug therapy / Q000378:metabolism*; D004311:Double-Blind Method; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008055:Lipids / Q000032:analysis; D008875:Middle Aged; D017698:Postmenopause
chemical_list: D000596:Amino Acids; D000924:Anticholesteremic Agents; D015415:Biomarkers; C418063:D-003 sugarcane wax acid mixture; D005227:Fatty Acids; D008055:Lipids; C036020:deoxypyridinoline; D000469:Alkaline Phosphatase