The effect of D-003 (10 mg/day) on biochemical parameters of bone remodelling in postmenopausal women: A randomized, double-blind study

International Journal of Clinical Pharmacology Research

Volumn 25, Issue 4, 2005, Pages 175-186

  Ceballos, A ^a   Mas, R ^b   Castano G ^a   Fernandez L ^b   Mendoza, S ^b   Menendez R ^b   Gonzalez J J ^a   Illnait, J ^b   Gamez R ^a,b   Mesa, M ^a   Fernandez J ^b  

^a Medical Surgical Research Center   (Cuba)

^b NATL CENTER FOR SCIENTIFIC RESEARCH   (Cuba)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALINE PHOSPHATASE BONE ISOENZYME; BIOCHEMICAL MARKER; CHOLESTEROL; CREATININE; D 003; DEOXYPYRIDINOLINE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LIPID; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; TRIACYLGLYCEROL;

ABDOMINAL PAIN; ADULT; ARTHRALGIA; ARTICLE; BONE DENSITY; BONE REMODELING; BONE TURNOVER; CHOLESTEROL BLOOD LEVEL; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; HEARTBURN; HUMAN; LIPID ANALYSIS; LIPOPROTEIN BLOOD LEVEL; LOW FAT DIET; OSSIFICATION; OSTEOLYSIS; POSTMENOPAUSE; POSTMENOPAUSE OSTEOPOROSIS; RANDOMIZED CONTROLLED TRIAL; STATISTICAL SIGNIFICANCE; TREATMENT WITHDRAWAL; TRIACYLGLYCEROL BLOOD LEVEL; URINARY EXCRETION;

ALKALINE PHOSPHATASE; AMINO ACIDS; ANTICHOLESTEREMIC AGENTS; BIOLOGICAL MARKERS; BONE DENSITY; BONE RESORPTION; DOUBLE-BLIND METHOD; FATTY ACIDS; FEMALE; HUMANS; LIPIDS; MIDDLE AGED; POSTMENOPAUSE;

EID: 29144485544     PISSN: 02511649     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (62)

1. Kanis J.A., Delmas P., Burchhardt P., et al. Guidelines for diagnosis and management of osteoporosis. Osteoporosis Int., 7, 390, 1997.
2. Burnett J.R., Vasikaran S.D. Cardiovascular disease and osteoporosis: Is there a link between lipids and bone? Ann. Clin. Biochem., 39, 203, 2002.
3. Mc Farlane S.I., Muniyappa R., Shin J.J. Osteoporosis and cardiovascular disease: Brittle bones and boned arteries. Is there a link? Endocrine, 23, 1, 2004.
4. Doggrell S.A. Present and future pharmacotherapy for osteoporosis. Drugs Today, 39, 633, 2003.
5. Delmas P. Treatment of postmenopausal osteoporosis. Lancet, 359, 2018, 2002.
6. Luckman S.P, Hughes D.E., Coxon F.P., Graham R., Russell G., Rogers M.J. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J. Bone Miner. Res., 13, 581, 1998.
7. Zhang F.L., Casey P.J. Protein prenylation: Molecular mechanisms and functional consequences. Annu. Rev. Biochem., 65, 241, 1996.
8. Van Beek E., Lowik C., Van der Pluijm G., Papapoulos S. The role of geranylgeranylation in bone resorption and its suppression by bisphosphonates in fetal bone explants in vitro: A clue to the mechanism of action of nitrogen-containing bisphosphonates. J. Bone Miner. Res., 14, 722, 1999.
9. Bauer D.C. HMG CoA reductase inhibitors and the skeleton: A comprehensive review. Osteopor. Int., 14, 273, 2003.
10. Staal A., Frith J.C., French M.H., et al. The ability of statins to inhibit bone resorption is directly related to their inhibitory effect on HMG-CoA reductase activity. J. Bone Miner. Res., 18, 88, 2003.
11. Mundy G., Garrett R., Harris S., et al. Stimulation of bone formation in vitro and in rodents by statins. Science, 286, 1946, 1999.
12. Garrett R., Mundy G.R. The role of statins as potential targets for bone formation. Arthritis Res., 4, 237, 2002.
13. Garrett I.R., Esparza J., Chen D., et al. Statins mediate their effects on osteoblasts by inhibition of HMG-CoA reductase and ultimately BMP2. J. Bone Min. Res., 15(Suppl.), S225, 2000.
14. Sugiyama M., Kodama T., Konishi K., et al. Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells. Biochem. Biophys. Res. Commun., 271, 688, 2000.
15. Wozney J.M., Rosen V. Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. Clin. Orthop., 346, 26, 1998.
16. Bauer D.C., Mundy G.R., Jamal S.A., et al. Statin use, bone mass and fracture: An analysis of two prospective studies. J. Bone Min. Res., 14, 1188, 1999.
17. Bauer D.C., Mundy G.R., Jamal S.A., et al. Use of statins and fracture: Results of 4 prospective studies and cumulative meta-analysis of observational studies and controlled trials. Arch. Intern. Med., 164, 146, 2004.
18. Edwards C.J., Hart D.J., Spector T.D. Oral statins and increased bone-mineral density in postmenopausal women. Lancet, 355, 2218, 2000.
19. Meier C.R., Schlieriger R.G., Kraenzlin M.E., et al. HMG-CoA reductase inhibitors and the risk of fractures. JAMA, 283, 3205, 2000.
20. Wang P.S., Solomon D.H., Mogun H., Avorn J. HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients. JAMA, 283, 3211, 2000.
21. Chan K.A., Andrade S.E., Boles M., et al. Inhibitors of hydroxymethylglutaryl-coenzyme A reductase and risk of fracture among older women. Lancet, 355, 2185, 2000.
22. Pasco J.A., Kotowicz M.A., Henry M.J., et al. Geelong Osteoporosis Study. Statin use, bone mineral density, and fracture risk: Geelong Osteoporosis Study. Arch. Intern. Med., 162, 537, 2002.
23. Montagnani A., Gonnelli S., Cepollaro C., et al. Effect of simvastatin treatment on bone mineral density and bone turnover in hypercholesterolemic postmenopausal women: A 1-year longitudinal study. Bone, 32, 427, 2003.
24. Lupattelli G., Scarponi A.M., Vaudo G., et al. Simvastatin increases bone mineral density in hypercholesterolemic postmenopausal women. Metabolism, 53, 744, 2004.
25. Reid I.R., Hague W., Emberson J., et al. Effect of pravastatin on frequency of fracture in the LIPID study: Secondary analysis of a randomised controlled trial. Long-term intervention with pravastatin in ischaemic disease. Lancet, 357, 509, 2001.
26. Rejnmark L., Buus N.M., Vestergaard R, et al. Effects of simvastatin on bone turnover and BMD: A 1-year randomized controlled trial in postmenopausal osteopenic women. J. Bone Miner. Res., 19, 737, 2004.
27. Parhami F., Morrow A., Balucan J., Tintut Y. Lipid oxidation products have opposite effects on calcifying vascular cell and bone cell differentiation. A possible explanation for the paradox of arterial calcification in osteoporotic patients. Arterioscler. Thromb. Vasc. Biol., 17, 680, 1997.
28. Xu H., Watkins B., Seifert M. Vitamin E stimulates trabecular bone formation and alters epiphyseal cartilage morphometry. Calc. Tissue Int., 57, 293, 1995.
29. Meunier P.J., Delmas P.D., Eastell R., et al. Diagnosis and management of osteoporosis in postmenopausal women: Clinical guidelines. Clin. Ther., 21, 1025, 1999.
30. Delmas P.D., Eastell R., Seibel M.J. The use of biochemical markers of bone turnover in osteoporosis. Osteoporosis Int., Suppl. 6, S2, 2000.
31. Bettica R, Bevilacqua M., Vago T., et al. Short-term variations in bone remodeling biochemical markers: Cyclical etidronate and alendronate effects compared. Clin. Endocrinol. Metab., 82, 3034, 1997.
32. Mas R. D-003: A new substance with promising lipid modifying and pleiotropic effects for atherosclerosis management. Drugs of the Future, 29, 773, 2004.
33. Menéndez R., Mas R., Amor A.M., et al. Inhibition of cholesterol biosynthesis in cultured fibroblasts by D-003, a mixture of very long chain saturated fatty acids. Pharmacol. Res., 44, 300, 2001.
34. Gámez R., Mendoza S., Más R., et al. Dose-dependent cholesterol-lowering effects of D-003 on normocholesterolemic rabbits. Curr. Ther. Res., 61, 8, 2000.
35. Mendoza S., Gámez R., Noa M., et al. Comparison of the effects of D-003 and policosanol on the lipid profile and endothelial cells in normocholesterolemic rabbits: A head to head comparison. Curr. Ther. Res., 62, 209, 2001.
36. Menéndez R., Más R., Pérez J., et al. Oral administration of D-003, a mixture of very long chain saturated fatty acids, prevents casein-induced endogenous hypercholesterolemia in rabbits. Can. J. Physiol. Pharmacol., 82, 22, 2003.
37. Castaño G., Mas R., Fernández L., et al. Assessment of the effects of D-003, a new antiplatelet and hypocholesterolemic compound on healthy volunteers: A phase I clinical study. Drugs R&D, 3, 337, 2002.
38. Castaño G., Menéndez R., Mas R., et al. Effects of D-003 on lipid profile and lipid peroxidation in healthy volunteers. Clin. Drug Invest., 23, 193, 2003.
39. Castaño G., Mas R., Fernández L., et al. Effects of D-003 (5-40 mg/day) on lipid profile of patients with type II hypercholesterolemia: A phase II clinical study. Clin. Drug Invest., 23, 789, 2003.
40. Menéndez R., Mas R., Pérez Y, et al. Inhibition of rat lipoprotein lipid peroxidation by the oral administration of D-003, a mixture of very long chain saturated fatty acids. Can. J. Physiol. Pharmacol., 80, 13, 2002.
41. Noa M., Más R., Mendoza S., Gámez R., Mendoza N. Effects of D-003, a mixture of high molecular weight aliphatic acids from sugar cane wax, on bones from ovariectomized rats. Drugs Exptl. Clin. Res., 30, 35, 2004.
42. Noa M., Mendoza S., Más R., Mendoza N., León F. Effect of D-003, a mixture of very high molecular weight aliphatic acids, on prednisolone-induced osteoporosis in Sprague Dawley rats. Drugs R&D, 5, 281, 2004.
43. Seigler L., Wu W.T. Separation of serum high-density lipoprotein for cholesterol determination: Ultracentrifugation vs precipitation with sodium phosphotungstate and magnesium chloride. Clin. Chem., 27, 838, 1981.
44. Friedewald W.T., Levy I.R., Fredrickson D.S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem., 18, 499, 1972.
45. O'Brien P.C., Shampo M.A. Statistical considerations for performing multiple tests in a single experiment. Comparing two therapies with respect to several endpoints. Mayo Clin. Proc., 63, 1140, 1988.
46. Seibel M.J., Robins S.P., Bilezikian J.P. Urinary pyridinium crosslinks of collagen: Specific markers of bone resorption in metabolic bone disease. Trends Endocrinol. Metab., 3, 263, 1992.
47. Stein G.S., Lian J.B., Owen T.A. Relationship of cell growth to the regulation of tissue-specific gene expression during osteoblast differentiation. FASEB J., 4, 3111, 1990.
48. Bettica P., Moro L., Robins S., et al. Sone resorption markers: Galactosyl hydroxylysine, pyridinium crosslinks, hydroxyproline compared. Clin. Chem., 38, 2313, 1992.
49. Bettica P, Taylor A.K., Talbot J., et al. Clinical performances of galactosyl hydroxylysine, pyridinoline and deoxypyridinoline in postmenopausal osteoporosis. J. Clin. Endocrinol. Metab., 81, 542, 1996.
50. Harris S.T., Gertz B.J., Genant H.K., et al. The effect of short term treatment with alendronate on vertebral density and biochemical markers of bone remodeling in early postmenopausal women. J. Clin. Endocrinol. Metab., 76, 1399, 1993.
51. Yang T.S., Tsan S.H., Chen C.R., et al. Effects of alendronate on bone turnover markers in early postmenopausal women. Zhonghua Yi Xue Za Zhi (Taipei), 61, 568, 1998.
52. Mallmin H., Ljunghall S., Larsson K., Lindh E. Short-term effects of pamidronate on biochemical markers of bone metabolism in osteoporosis-a placebo-controlled dose-finding study. Ups. J. Med. Sci., 96, 205, 1991.
53. Chan M.H., Mak T.W., Chiu R.W., et al. Simvastatin increases serum osteocalcin concentration in patients treated for hypercholesterolaemia. J. Clin. Endocrinol. Metab., 86, 4556, 2001.
54. Stein E.A., Farnier M., Waldstreicher J., Mercuri M., Simvastatin/Atorvastatin Study Group. Effects of statins on biomarkers of bone metabolism: A randomised trial. Nutr. Metab. Cardiovasc. Dis., 11, 84, 2001.
55. Tikiz C., Unlu Z., Tikiz H., Ay K., et al. The effect of simvastatin on serum cytokine levels and bone metabolism in post-menopausal subjects: Negative correlation between TNF-alpha and anabolic bone parameters. J. Bone Miner. Metab., 22, 365, 2004.
56. von Stechow D., Fish S., Yahalom D., et al. Does simvastatin stimulate bone formation in vivo? BMC Musculoskeletal Disorders, 4, 1471, 2003.
57. Mostaza J.M., De la Piedra C., Curiel M.D., et al. Pravastatin therapy increases procollagen I N-terminal propeptide (PINP), a marker of bone formation in post-menopausal women. Clin. Chim. Acta., 308, 133, 2001.
58. Bjarnason N.H., Riis B.J., Christiansen C. The effect of fluvastatin on parameters of bone remodelling. Osteoporos. Int., 12, 380, 2001.
59. Berthold H.K., Unverdorben S., Zittermann A., et al. Age-dependent effects of atorvastatin on biochemical bone turnover markers: A randomized controlled trial in postmenopausal women. Osteoporos. Int., 15, 459, 2004.
60. Braatvedt G.D., Bagg W., Gamble G., et al. The effect of atorvastatin on markers of bone turnover in patients with type 2 diabetes. Bone, 35, 766, 2004.
61. Seifert M.F., Watkins B.A. Role of dietary lipid and antioxidants on bone metabolism. Nutr. Res., 17, 1209, 1997.
62. Horcajada-Molteni M.N., Crespy V., Coxam V., et al. Routine inhibits ovariectomy-induced osteopenia in rats. J. Bone Min. Res., 15, 2251, 1997.