The impact of statin therapy on bone density changes in postmenopausal women

Česká verzia

Authors: P. Švejda ¹; V. Soška ²; M. Souček ¹
Authors place of work: II. interní klinika Lékařské fakulty MU a FN u sv. Anny, Brno, přednosta doc. MUDr. Miroslav Souček, CSc. ¹; Oddělení klinické biochemie FN u sv. Anny, Brno, přednosta doc. MUDr. Vladimír Soška, CSc. ²
Published in the journal: Vnitř Lék 2007; 53(10): 1064-1070
Category: Original Contributions

Summary

Generalised use of statins in primary and secondary prevention of ischemic heart disease has led in recent years to the discovery of a number of other „pleiotropic“ effects of statins. One of them is the effect of statins on bone metabolism. The objective of the study was to monitor bone density, bone turnover markers and basic biochemical parameters in a group of postmenopausal women at regular intervals for a period of 2 years. The monitoring allowed for an assessment of the effect of statin therapy on those parameters. Statin therapy safety was also monitored. According to expectations, the group receiving active treatment recorded a decrease in the levels of total cholesterol, as well as LDL-cholesterol, and a mild decrease in the level of triacylglycerols. However, no significant difference in bone density in any of the measured regions (NECK, TROCH, SHAFT) was found when the trends in bone density parameters were compared for the two groups, nor there was a significant change in the respective T-scores. There was no significant difference with respect to the markers of bone formation or the markers of bone resorption between the group with active treatment and the control group. The results correspond to inconsistent data from the performed and quoted retrospective and prospective studies.

Keywords:
statins – bone density – bone turnover – osteoporosis

Zdroje

1. Alberts AW, Chen J, Kuron G et al. Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proc Natl Acad Sci USA 1980; 77: 3957-3961.

2. Alegret M, Silvestre JS. Pleiotropic effects of statins and related pharmacological experimental approaches. Clin Pharmacol 2006; 28: 627-656.

3. Ascaso J, Gonzalez Santos P, Hernandez Mijares A et al. Management of dyslipidemia in the metabolic syndrome: recommendations of the Spanish HDL-Forum. Am J Cardiovasc Drugs 2007; 7: 39-58.

4. Bauer DC, Mundy GR, Jamal SA et al. Statin use, bone mass and fracture: an analysis of two prospective studies (abstract). J Bone Miner Res 1999; 14: S179.

5. Broulík P. Osteoporosa. Praha: Maxdorf 1999.

6. Cummings SR, Black DM, Thompson DE 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 1998; 280; 2077-2082.

7. Češka R et al. Cholesterol a ateroskleróza, léčba dyslipidémií. Praha: Triton 2005.

8. Edwards CJ, Hart DJ, Spector TD et al. Oral statins and increased bone-mineral density in postmenopausal women. Lancet 2000; 355: 2218-2219.

9. Funkhouser HL, Adera T, Adler RA. Effect of HMG-CoA reductase inhibitors on bone mineral density. J Clin Densitom 2002; 5: 151-158.

10. Greenspan SL, Holland S, Maitland RL et al. Alendronate stimulation of nocturnal parathyroid hormone secretion: a mechanism to explain the continued improvement in bone mineral sensity accompanying alendronate therapy. Proc Assoc Am Physicians 1996; 108: 230-238.

11. Hamelin BA, Turgeon J. Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors. Trends Pharmacol Sci 1998; 19: 26-37.

12. Harris SE. Recombinant bone morphogenetic protein 2 accelerates bone cell differentiation and stimulation BMP 2 mRNA expression and BMP 2 promoter activity in primary fetal rat calvarial osteoblast cultures. Moll Cell Diff 1997; 3: 37-155.

13. Heiss C, Keller T, Wehr U et al. Biochemical bone marrow markers and their significance in postmenopausal osteoporosis--a new method in the diagnosis of osteoporosis? Biomed Tech (Berl) 2004; 49: 282-289.

14. Chung YS, Lee MD, Lee SK et al. HMG-CoA reductase inhibitors increase BMD in type 2 diabetes mellitus patients. J Clin Endocrinol Metab 2000; 85: 1137-1142.

15. Inaba M, Nishizawa Y, Mita K et al. Poor glycemic control impairs the response of biochemical parameters of bone formation and resorption to exogenous 1,25-dihydroxy- vitamin D3 in patients with type 2 diabetes. Osteoporosis Int 1999; 9: 525-531.

16. Ishimi Y. The role of mevalonate pathway in osteogenic cells. Nippon Rinsho 2004; 62(Suppl 2): 779-782.

17. Karpf DB, Shapiro DR, Seeman E et al. Prevention of nonvertebral fractures by alendronate: a meta-analysis. Alendronate Osteoporosis Treatment Study Group. JAMA 1997; 277: 1159-1164.

18. Kelly PJ, Pocock NA, Sambrook PN et al. Age- and menopause-related changes in indices of bone turnover. J Clin Endocrinol Metab 1989; 69: 1160-1165.

19. LaCroix AZ, Cauley JA, Jackson R et al. Does statin use reduce risk of fracture in postmenopausal women? Results from the Women’s Health Initiative Observational Study (WHI-OS; abstract). J Bone Miner Res 2000; 15(Suppl 1): 1066.

20. Levy JR, Murray E, Manolagas S et al. Demonstration of insulin receptors and modulation of alkaline phosphatase activity by insulin in rat osteoblastic cells. Endocrinology 1986; 119: 1786-1792.

21. Luckman SP, Hughes DE, Coxon FP et al. Nitrogencontaining bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res 1998; 13: 581-589.

22. Luegmayr E, Glantschnig H, Wesolowski GA et al. Osteoclast formation, survival and morphology are highly dependent on exogenous cholesterol/lipoproteins. Cell Death Differ 2004; 1(Suppl 1): 108-118.

23. McClung MR, Geusens P, Miller PD 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.

24. Morton DJ, Barret Connor EL et al. Thiazides and bone mineral density in elderly men and women. Am J Epidemiol 1994; 139: 1107-1115.

25. Mundy G, Garrett R, Harris S et al. Stimulation of bone formation in vitro and in rodents by statins. Science 1999; 286: 1946-1949.

26. Parhami F, Garfinkel A, Demer LL. Role of lipid in osteoporosis. Arteriol Thromb Vasc Biol 2000; 20: 2346-2348.

27. Parhami, F, Morrow AD, Balucan J et al. Lipid oxidation products have opposite effects on calcifying vascular cell and bone cell differentiation. Arteriol Thromb Vasc Biol 1997; 17: 680-687.

28. Pharmindex - Brevíř 2006. Kardiologie-Angiologie. Medical Tribune 484-485.

29. Porcel ER, Lopez JL, Ferron MA et al. Effects of the sporulation conditions on the lovastatin production by Aspergillus terreus. Bioprocess Biosyst Eng 2006; 29: 1-5.

30. Rosen CJ. Biochemical markers of bone turnover. In: Rosen CJ (ed.) Osteoporosis: diagnostic and therapeutic principles. Totowa (NJ): Humana Press 1996, 129-141.

31. Seibel MJ, Cosman F, Shen V et al. Urinary hydroxypyridinium cross-links of collagen as markers of bone resorption and estrogen efficacy in postmenopausal osteoporosis. J Bone Miner Res 1993; 8: 881-889.

32. Švejda P. Statiny a osteoporóza. Vnitř Lék 2006; 52: 1190-1193.

33. Tannirandorn P, Epstein S. Drug-induced bone loss. Osteoporos Int 2000; 11: 637-659.

34. Van Beek E, Pieterman E, Cohen L et al. Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing bisphosphonates. Biochem Biophys Res Commun 1999; 264: 108-211.

35. Wasnich RD, Ross PD, Heilbrun LK et al. Differential effects of thiazide and estrogen upon bone mineral content and fracture prevalence. Obstet Gynecol 1986; 67: 457-462.

36. Watanabe S, Fukumoto S, Takeuchi Y et al. Effects of 1-year treatment with fluvastatin or pravastatin on bone. Am J Med 2001; 110: 584-587.

37. Zhang FL, Casey PJ. Protein prenylation: molecular mechanisms and functional consequences. Annu Rev Biochem 1996; 65: 241-269.