IJCRR - Vol 05 Issue 04, February, 2013
DO STATINS HAVE POTENTIAL AS ANTI OSTEOPOROTIC DRUGS AND CAN THEY BE USED FOR PREVENTION OR TARGETING OSTEOPOROSIS: A REVIEW
Author: Karmajeet Rath, Biswa Bhusan Mohanty, Sanjay Kumar, Pramila Nayak, Jagannath Sahoo
Inhibitors of HMG-CoA reductase enzymes, which are statins, are well known and much prescribed drugs for lowering of cholesterol and used for dyslipidemia. But, they have also been shown across various studies to stimulate bone formation. In bone cells, these inhibitors have been known to increase the gene expression of bone morphogenetic protein-2, thereby helping in osteoblastic differentiation, with some effects also on osteoclastic inhibition. The findings that statins can increase bone formation and thereby mass of bone, can be helpful in preventing bone fractures and improving osteoporosis, which is a condition of marked bone loss. Hence, it is reviewed herein that HMG-CoA reductase inhibitors can be a great way, probably a futuristic drug for osteoporotic treatment and prevention. Keywords: HMG-CoA reductase inhibitors, osteoporosis
Keywords: HMG-CoA reductase inhibitors, osteoporosis, osteoblasts, statins, bone metabolism, fracture
Karmajeet Rath, Biswa Bhusan Mohanty, Sanjay Kumar, Pramila Nayak, Jagannath Sahoo. DO STATINS HAVE POTENTIAL AS ANTI OSTEOPOROTIC DRUGS AND CAN THEY BE USED FOR PREVENTION OR TARGETING OSTEOPOROSIS: A REVIEW International Journal of Current Research and Review. Vol 05 Issue 04, February, 73-81
1. Data from the World Health Organization Assessment of osteoporosis at the primary health care level. Summary report of a WHO scientific Group 2007; WHO, Geneva.
2. Cole ZA, Dennison EM, Cooper C, 2008 Osteoporosis epidemiology update. Curr Rheumatol Rep 10: 92-96.
3. Nguyen ND, Ahlborg HG, Center JR, Eisman JA, Nguyen TV, 2007 Residual lifetime risk of fractures in women and men. J Bone Miner Res 22: 781-788.
4. Pinheiro MM, Reis Neto ET, Machado FS, et al, 2010 Risk factors for osteoporotic fractures and low bone density in pre and postmenopausal women. Rev Saude Publica 44: 479-485.
5. Glimcher MJ, Krane SM: The organizational and structure of bone and the mechanism of calcification. In: A treatise on collagen.Biology of collagens. Edited by Ramachandran GN, Goudl BS. New York: Academic Press; 1968:68-91.
6. Glimcher MJ: Comparison, structure and organization of bone and other mineralized tissues and the mechanism of calcification. In: Handbook of physiology, endocrinology, parathyroid gland. Edited by Aubarch GD. Washington: American Physiological Society; 1976:25-48
7. Al-Sebaie H, Al-Hefnawy A. Risk factors for osteoporosis. Egypt Rheum 1997; 24:209-219
8. Morrison N, Qi J, Tikota A, Kelly PJ, Crofts L, Nguyen TV, et al. Prediction of bone density for vitamin D receptor alleles. Nature 1994; 367:384-387.
9. Stuart H, Ralston M. What determines peak bone mass and bone loss. In: Bailliers Clinical Rheumatology, 3rd ed. Philadelphia: Catham Company 1997; 11:479-493.
10. Girasol G, Jjlka R, Passeri G. Estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells. J Clin Invset 1992; 89:883-891.
11. Grant S, Reid D, Blak G, Herd R, Fogelman I, Ralston SH. Reduced bone density and osteoporosis associated with a polymorphic site in the collagen type 1 alpha gene. Nature Genetics 1996; 14:203-205.
12. Vega D, Maalouf NM, Sakhaee K, 2007 Clinical review: the role of receptor activator of nuclear factor kappa B(RANK)/RANK ligand/osteoprotegerin clinical implications. J Clin Endocrinol Metab 92: 4514-45121.
13. Painter SE, Kleerekoper M, Camacho PM, 2006 Secondary osteoporosis: a review of the recent evidence. Endocr Pract 12: 436- 445.
14. Bagger YZ, Rasmussen HB, Alexandersen P, et al, 2007 PERF Study Group. Links between cardiovascular disease and osteoporosis in postmenopausal women: serum lipids or atherosclerosis per se? Osteoporos Int 18: 505-512.
15. Mundy G, Garrett R, Harris S, et al, 1999 Stimulation of bone formation in vitro and in rodents by statins. Science 286: 1946- 1949.
16. Chan KA, Andrade SE, Boles M, Buist DS, Chase GA,Donahue JG, et al. Inhibitors of hydroxymethylglutaryl-CoA reductase and risk of fracture among older women. Lancet 2000;355:2185-8.
17. Hughes A, Rogers MJ, Idris AI, et al, 2007 A Comparison between the Effects of Hydrophobic andHydrophilic Statins on Osteoclast Function In Vitro and Ovariectomy-Induced Bone Loss In Vivo. Calcif Tissue Int 81:403-413.
18. Pagkalos J, Cha JM, Kang Y, et al, 2010 Simvastatin induces osteogenic differentiation of murine embryonic stem cells. J Bone Miner Res, 25: 2470-2478.
19. Uzzan B, Cohen R, Nicolas P, Cucheratc M, Perret G. Effects of statins on bone mineral density: a meta-analysis of clinical studies. Bone 2007; 40:1581-1587.
20. Bauer DC, Mundy GR, Jamal SA, Black DM, Cauley JA, Harris F,Duong T, Cummings SR: Statin use, bone mass and fracture: an analysis of two prospective studies. J Bone Min Res 1999, 14:1188.
21. Chuengsamarn S, Rattanamongkoulgul S, Suwanwalaikorn S, Wattanasirichaigoon S, Kaufman L. Effects of statins vs. non-statin lipid-lowering therapy on bone formation and bone mineral density biomarkers in patients with hyperlipidemia. Bone 2010;46:1011-1015
22. Fisher JE, Rogers Mi, Halasy JM, Luckman SP, Hughes DE, Masarachia† PJ, et al. Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. Proc Natl Acad Sci USA 1999; 96:133 138.
23. Luckman SP, Hughes DE, Coxon FP, Russell RG, Rogers MJ. Nitrogencontaining bisphosphonates inhibit the mevalonate pathway and prevent posttranslational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res 1996; 13:581-589.
24. Luckman SP, Coxon FR, Ebetino FH, Russell RG, Rogers MJ. Heterocyclecontaining bisphosphonates cause apoptosis and inhibit bone resorption by preventing protein prenylation: evidence from structure-activity relationships in 1774 macrophages. J Bone Miner Res 1998; 13:1668-1678.
25. Zhang FL Casey PJ. Protein prenylation: molecular mechanisms and functional consequences. Annu Rev Biochem 1996; 65:241-269.
26. Van Beek E, Pieterman E, Cohen L, Lowik C, Papapoulos S. Farnesyl pyrophosphate synthase is the molecular target of nitrogencontaining biaphosphonates. Biochem Biophys Res Commun 1999; 264:108-211.
27. McClung MR, Geusens P, Miller PD, Zippel H, Bensen WG, Roux C, et al. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med 2001; 344:333- 340.
28. Karpf DB, Shapiro DR, Seeman E, Ensrud KE, Johnston CC Jr, Adami S, et al. Prevention of nonvertebral fractures by alendronate: a meta-analysis. Alendronate Osteoporosis Treatment Study Group. JAMA 1997; 277:1159-1164
29. Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 1996; 280:2077-2082
30. Mundy C, Garrett R, Harris S, Chan J, Chen D, Rossini G, et al. Stimulation of bone formation in vitro and in rodents by statins. Science 1999; 266:1946-1949.
31. Alberts AW, Chen J, Kuron G, Hunt V, Huff J, Hoffman C, et al. Mevinolin: a highly potent competitive inhibitor of hydroxymethyl-glutaryl - coenzyme A reductase and a cholesterol-lowering agent. Proc Natl Acad Sci USA 1980; 77:3957- 3961
32. Haffner SM, Alexander CM, Cook TJ, Boccuzzi SJ, Musliner TA, Pedersen TR, et al. Reduced coronary events in simvastatin treated patients with coronary heart disease and diabetes or impaired fasting glucose levels, subgroup analyses in the Scandinavian Simvastatin Survival Study. Arch Intern Med 1999; 159:2661-2667
33. Crisby M, Fredriksson-Norden G, Nillsson J. Pravastatin treatment decreases lipid content and cell death in human carotid plaques. Lancet 1998; 30:21-28.
34. Wai-Keilam C, Chan IH, Mundy G. Statins and bone formation. Science 2001; 31:27- 29.
35. Mesako S, Kodama. T, Konishi K. Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosacoma cells. Biochern Biophys Res Commun 2000; 271:688-6
36. Wang PS, Solomon DH, Morgan H, Avorn J. HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients. JAMA 2000; 283:3211-3216
37. Chuengsamarn S, Rattanamongkoulgul S, Suwanwalaikorn S, Wattanasirichaigoon S, Kaufman L. Effects of statins vs. non-statin lipid-lowering therapy on bone formation and bone mineral density biomarkers in patients with hyperlipidemia. Bone 2010;46:1011-1015
38. Maeda T, Matsunuma A, Kawane T, Horiuchi N: Simvastatin promotes osteoblast differentiation and mineralization in MC3T3-E1 cells. Biochem Biophys Res Commun 2001, 280: 874-877.
39. Bauer DC, Mundy GR, Jamal SA, Black DM, Cauley JA, Harris F, Duong T, Cummings SR: Statin use, bone mass and fracture: an analysis of two prospective studies. J Bone Min Res 1999, 14:1188
40. Edwards CJ, Hart DJ, Spector TD: Oral statins and increased bone-mineral density in postmenopausal women. Lancet 2000, 355:2218-2219.
41. Wang PS, Solomon DH, Mogun H, Avorn J: HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients. JAMA 2000, 283:3211-3216.24.
42. Meier CR, Schlienger RG, Kraenzlin ME, Schlegel B, Jick H: Statin drugs and the risk of fracture. JAMA 2000, 284:1921-1922,)
43. van Staa TP, Wegman SLJ, de Vries F, Leufkens HGM, Cooper C: Use of statins and risk of fractures [abstract 1067]. J BoneMin Res 2000, 15(suppl):s155.
44. Cauley JA, Jackson R, Pettinger M, Lacroix A, Bauer D, Chen Z, Daugherty S, Hsia J, Lewis CE, McGowan J, McNeeley SG, Passaro M: Statin use and bone mineral density (BMD) in older women: The Women’s Health Initiative Observational Study (WH I-OS) [abstract 1068]. J Bone Min Res 2000,15(suppl):s155.