Статья
Атеросклероз и остеопороз. Общие мишени для влияния сердечно-сосудистых и антиостеопорозных препаратов (Часть I). Влияние сердечно-сосудистых препаратов на прочность костной ткани
Повседневное применение в клинической практике гипотензивных и липидснижающих препаратов диктует необходимость знаний их разнообразных плейотропных эффектов. В статье представлены результаты работ по влиянию сердечно-сосудистых препаратов, таких как статины, бета-адреноблокаторы, ингибиторы ангиотензин-превращающего фермента, диуретики, антагонисты кальция и нитраты на минеральную плотность кости и развитие переломов, связанных с остеопорозом. Раскрыты механизмы действия препаратов на костную массу, маркеры костного метаболизма, на частоту переломов при остеопорозе. Большинство работ свидетельствуют о том, что использование кардиологических препаратов наряду с положительным влиянием на сосудистую стенку замедляют костную резорбцию и повышают костную массу. Знания о дополнительном влиянии на костный обмен сердечно-сосудистых препаратов позволят выбрать адекватную терапию и улучшить прогноз обоих заболеваний.
1. Dennison T.M., Cooper C. Osteoporosis in 2010: building bones and (safely) preventing breaks. Nat Rev Rheumatol. 2011;7(1):80-2. doi:10.1038/nrrheum.2010.227.
2. Crepaldi G., Maggi S. Epidemiologic link between osteoporosis and cardiovascular disease. J Endocrinol Invest. 2009;32(4):2-5.
3. Pfister R., Mishels G., Sharp S.J. et al. Low bone mineral density predicts incidents heart failure in man and women: the EPIC (European Prospective Investigation Into Cancer and Nutrition) - Norfolk Prospective Study. JACC: Heart failure. 2014:2(4):380-9. doi:10.1016/j.jchf.2014.03.010.
4. Veronese N., Stubbs B., Crepaldi G. et al. Relationship between low bone mineral density and fractures with incidence cardiovascular desease: A systematic review and meta-analysis. J Bone Miner Res. 2017;32(5):1126-35. doi.org/10.1002/jbmr.3089.
5. den Uyl D., Nurmohamed M.T., Tuyl van L.H. et. al. (Sub)clinical cardiovascular disease is associated with increased bone loss and fracture risk; a systematic review of the association between cardiovascular disease and osteoporosis. Arthritis Res Ther. 2011;13:R5. doi:10.1186/ar3224.
6. Hofbauer L.C, Brueck C.C, Shanahan C.M., et al. Vascular calcification and osteoporosis – from clinical observation towards molecular understanding. Osteoporos Int. 2007;18(3):251-9. doi:10.1007/s00198-006-0282-z.
7. Liu J., Zhu L.P., Yang X.L. et al. HMG-CoA reductase inhibitors (statins) and bone mineral density: a meta-analysis. Bone. 2013;54(1):151-6. doi:10.1016/j.bone.2013.01.044.
8. Dai L., Xu M., Wu H. et al. The functional mechanism of simvastatin in experimental osteoporosis. Journal of Bone and Mineral Metabolism. 2016;34:23-32. doi:10.1007/s00774-014-0638-y.
9. Wong S.Y., Lynn H., Kwok T. et al. Angiotensin converting enzyme inhibitor use is associated with higher bone mineral density in elderly Chinese. Bone. 2014;34(4):584-88. doi:10.1016/j.bone.2005.09.011.
10. Mundi G., Garret S., Harris S. et al. Stimulation of bone formation in vitro and in rodents by statins. Science. 2009;286:1946-49. doi:10.1126/science.286.5446.1946.
11. Stark W., Blaskovich M., Johnson B. et al. Inhibiting geranylgeranylation blocks growth and promotes apoptosis in pulmonary vascular smooth muscle cells. American journal of physiology 1998;275: 55-63.
12. Vickers S., Duncan C.A., Chen I.W. et al. Metabolic disposition studies on simvastatin, a cholesterollowering prodrug. Drug Metab Dispos. 2000;18:138-45.
13. LaCroix A.Z., Cauley J., LaCroix A.Z. et al. Statin use, clinical fracture, and bone density in postmenopausal women: results from the Women's Health Initiative Observational Study. Ann Intern Med. 2003;139(2):97-104. doi:10.7326/0003-4819-139-2-200307150-00009.
14. Chan M.H., Mak T.W., Chiu R.W. et al. Simvastatin increases serum osteocalcin concentration in patients treated for hypercholesterolemia. J Clin Endocrinol Metab. 2001; 86:4556-59. doi:10.1210/jcem.86.9.8001.
15. Edwards C.J., Hart D.J., Spector T.D. Oral statins and increased bone mineral density in postmenopausal women. Lancet. 2000;355:2218-19. doi:10.1016/S0140-6736(00)02408-9.
16. Chung Y.S., Lee M.D., Lee S.K. et al. HMG-CoA reductase inhibitors increase BMD in type 2 diabetes mellitus patients. J Clin Endocrinol Metab. 2000;85:1137-42. doi:10.1210/jcem.85.3.6476.
17. Hatzigeorgiou C., Jackson J.L. Hydroxymethylglutaryl-coenzyme-A reductase inhibitors and osteoporosis: a meta-analysis. Osteoporos Int. 2005;16:990-98. doi:10.1007/s00198-004-1793-0.
18. Rejnmark L., Vestergaard P., Mosekilde L. Statin but not non-statin lipid-lowering drugs decrease fracture risk: A nation-wide case-control study. Calcif Tissue Int. 2006;79:27-36. doi:10.2147/CLEP.S145311.
19. Wang P.S., Solomon D.H., Mogun H. et al. HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients. JAMA. 2010;283:3211-16. doi:10.1001/jama.283.24.3211.
20. Gong Ja., Wang Z., Lee Yi. et al. Effect of statins on bone mineral density and fracture rick: A PRISMAcompliant systematic review and meta-analysis. Medicine. 2016;95(22):e3042. doi:10.1097/MD.0000000000003042.
21. Wang X.Y., Masilamani S., Nielsen J. et al. The renal thiazide-sensitive Na-Cl cotransporter as mediator of the aldosterone-escape phenomenon. J Clin Invest. 2011;108:215-22. doi:10.1172/JCI10366.
22. Dvorak M.M., De Joussineau C., Carter D.H. et al. Thiazide diuretics directly induce osteoblast differentiation and mineralized nodule formation by interacting with a sodium chloride co-transporter in bone. J Am Soc Nephrol. 2007;18:2509-16. doi:10.1681/ASN.2007030348.
23. Rejnmark L., Vestergaard P., Ped A.R. et al. Dose-effect relations of loop - and thiazide-diuretics on calcium homeostasis: a randomized, double blinded Latin-square multiple cross-over study in postmenopausal osteopenic women. Eur J Clin Invest. 2003;33:41-50. doi:10.1046/j.1365-2362.2003.01103.x.
24. Sigurdsson G., Franzson L. Increased bone mineral density in a population-based group of 70-yearold women on thiazide diuretics, independent of parathyroid hormone levels. J Intern Med. 2001;250:51-6. doi:10.1046/j.1365-2796.2001.00850.x.
25. Aung K., Htay T. Thiazide diuretics and the risk of hip fracture. Cochrane Database Syst. Rev. 2011;10:CD005185. doi:10.1002/14651858.CD005185.
26. Barzilay J.I., Davis B.R., Pressel S.L. et al. The impact of antihypertensive medication on Bone Mineral density and fracture risk. Current Cardiology Report. 2017;19(76):176-84. doi:10.1007/s11886-017-0888-0.
27. Rejnmark L., Vestergaard P., Heickendorff L. et al. Loop diuretics increase bone turnover and decrease BMD in osteopenic postmenopausal women: results from a randomized controlled study with bumetanide. J Bone Miner Res. 2006;21:163-70. doi:10.1359/JBMR.051003.
28. Solomon D.H., Mogun H., Garneau K. et al. Risk of fractures in older adults using antihypertensive medications. J Bone Miner Res. 2011;26:1561-7. doi:10.1002/jbmr.356.
29. Bonnet N., Gadois C., McCloskey E. et al. Protective effect of beta-blockers in postmenopausal women: influence on fractures, bone density, micro and macroarchitecture. Bone. 2008;40:1209- 16. doi:10.1016/j.bone.2007.01.006.
30. Weins M., Etminan M., Gill S.S. et al. Effects of antihypertensive drug treatments on fractures outcomes: a meta-analysis of observational studies. Journal of International Studies. 2006;260:350- 62. doi:10.1111/j.1365-2796.2006.01695.x.
31. Rejnmark L., Vestergaard P., Kassem M. et.al. Fracture risk in perimenopausal women treated with beta-blockers. Calcif Tissue Int. 2004;75:365-72. doi:10.1007/s00223-004-0222-x.
32. Pasco J.A., Henry M.J., Nicholson G.C. et.al. B-blockers reduce bone resorption marker in early postmenopausal women. Ann Human Biol. 2005;32:738-45. doi:10.1080/03014460500292168.
33. Скрипникова И.А., Собченко К.Е., Косматова О.В., Небиеридзе Д.В. Влияние сердечно-сосудистых препаратов на костную ткань и возможность их использования для профилактики остеопороза. Рациональная Фармакотерапия в Кардиологии. 2012;8(4):587-94. doi:10.20996/1819-6446-2012-8-4-587-594.
34. Yang S., Nguyen N.D., Center J.R. et al. Association between beta-blocker use and fracture risk the Dubbo Osteoporosis Epidemiology Study. Bone. 2011;48(3):451-55. doi:10.1016/j.bone.2010. 10.170.
35. Turker S., Karatosun V., Gunai I. Beta-blockers increase bone mineral density. Clin Orthop. 2006;443:73-4. doi:10.1097/01.blo.0000200242.52802.6d.
36. Pasco J.A., Henry M.J., Sanders K.M. et al. Beta-adrenergic blockers reduce the risk of fracture partly by increasing bone mineral density: Geelong Osteoporosis Study. J Bone Miner Res. 2004; 19: 19-24. doi:1359/JBMR.0301214.
37. Schlienger R.G., Kraenzlin M.E., Jick S.S. et al. Use of beta-blockers and risk of fractures. JAMA. 2004;292:1326-32. doi:10.1001/jama.292.11.1326.
38. de Vries F., Souverein P.C., Leufkens H.G. et al. Use of beta-blockers and the risk of hip/femur fracture in the United Kingdom and the Netherlands. Calcif Tissue Int. 2007;80:69-75. doi:10.1007/s00223-006-0213-1.
39. Rejnmark L., Vestergaard P., Mosekilde L. Treatment with beta-blockers, ACE inhibitors, and calciumchannel blockers is associated with a reduced fracture risk: a nationwide case-control study. J Hypertens. 2006;24:581-89. doi:10.1097/01.hjh.0000203845.26690.cb.
40. Reid I.R., Gamble G.D., Grey A.B. et al. Beta-blockers use, BMD, and fractures in the study of osteoporotic fractures. J Bone Miner Res. 2005;20:613-18. doi:10.1359/JBMR.041202.
41. Toker A., Gulcan E., Toker S. et al. Nebivolol might be beneficial in osteoporosis treatment: a hypothesis. TJPR. 2009; (2):181-86. doi:10.4314/tjpr.v8i2.44528.
42. Тепоян И.Л., Небиеридзе Д.В., Скрипникова И.А. и др. Сравнительная оценка плейотропных эффектов небиволола и атенолола на параметры микроциркуляции и костную ткань у женщин постменопаузального периода с мягкой артериальной гипертонией. Кардиоваскулярная Терапия и Профилактика. 2016;15(2):26-31. doi:10.15829/1728-8800-2016-2-26-31.
43. Брошусь В.В. Оксид азота как регулятор защитных и гомеостатических реакций организма. Украинский Ревматологический Журнал. 2003;4:3-11.
44. Lavasseur R., Marcelli C., Savatier J.p. et al. Beta-blockers use, BMD, and fractures risk in older women: results from the Epidemiologie de L’Osteoporose Prospective Study. J Am Geriatr Soc 2005;53:550-52. doi:10.1111/j.1532-5415.2005.53178_7.x.
45. Reid I.R., Gamble G.D., Grey A.B et al. Beta-blockers use, BMD, and fractures in the study of osteoporotic fractures. J Bone Miner Resю 2005;20:613-18. doi:10.1359/JBMR.041202.
46. Hatton R., Stimpel M., Chambers T.J. Angiotensin II is generated from angiotensin I by bone cells and stimulates osteoclastic bone resorption in vitro. J Endocrinol. 2007;152:5-10. doi:10.1677/joe. 0.1520005.
47. Nakagami H., Morishita R. Hormones and osteoporosis update. Effect of angiotensin II on bone metabolism. Clin Calcium. 2009;19:997-1002.
48. Bleicher K., Cumming R.G., Naganathan V. Predictors of the rate of BMD loss in older men: findings from the CHAMP study. Osteoporos Int. 2013;24(7):1951-63. doi:10.1007/s00198- 012-2226-0.
49. Zaidi M., MacIntyre I., Datta H. Intracellular calcium in the control of osteoclast function. II. Paradoxical elevation of cytosolic free calcium by verapamil. Biochemical and Biophysical Research Communications. 1990;167(2):807-12. doi:10.1016/0006-291X (90)92097.
50. Zacharieva S., Shigarminova R., Nachev E. et al. Effect of amlodipine and hormone replacement ther - apy on blood pressure and bone markers in menopause. Methods Find Exp Clin Pharmacol. 2003;25:209-13. doi:10.1358/mf.2003.25.3.769642.
51. Ağaçayak K.S., Güven S., Koparal M. et al. Long-term effects of antihypertensive medications on bone mineral density in men older than 55 years. Clin Interv Aging. 2014;9:509-13. doi:10.2147/CIA.S60669.
52. Solomon D.H., Mogun H., Garneau K. et al. Risk of fractures in older adults using antihypertensive medications. J Bone Miner Res. 2011;26:1561-67. doi:10.1002/jbmr.356.
53. Ruths S., Bakken M.S., Rantoff A.H. et al. Risk of hip fracture among older people using antihypertensivedrugs: a nationwide cohort study. BMC Geriatrics. 2015.15:153-62. doi:10.1186/s12877- 015-0154-5.
54. Ralston S.H., Ho L., Helfrich M.H. et al. Nitric oxide: A cytokine-induced regulator of bone resorption. J Bone Miner Res. 1995;10:1040-9. doi:10.1002/jbmr.5650100708.
55. Jamal S.A., Browner W.S., Bauer D.C., Cummings S.R. Intermittent use of nitrates increases bone mineral density: the study of osteoporotic fractures. J Bone Miner Res. 1998;13(11):1755-9. doi:10.1359/jbmr.1998.13.11.1755.
56. Rejnmark L., Vestergaard P., Mosekilde L. Decreased fracture risk in users of organic nitrates: a nationwide case-control study. J Bone Miner Res. 2006;21:1811-7. doi:10.1359/jbmr.060804.
57. Jamal S.A., Cummings S.R., Hawker G.A. Isosorbide mononitrate increases bone formation and decreases bone resorption in postmenopausal women: a randomized trial. J Bone Miner Res. 2004;19:1512-7. doi:10.1359/JBMR.040716.
58. Golchin N., Hohensee C., LaCroix A. Nitrate Medications, Fractures, and Change in Bone Mineral Density in Postmenopausal Women: Results from the Women's Health Initiative. J Bone Miner Res. 2016;31(9):1760-6. doi:10.1002/jbmr.2838.
59. Rejnmark L., Vestergaard P., Mosekilde L. Fracture risk in patients treated with amiodarone or digoxin for cardiac arrhythmias: a nation-wide case-control study. Osteoporosis Int. 2009;18:409-17. doi:10.1007/s00198-006-0250-7.
60. Gandavati A., Hajjar I., Quach L. et al. Hypertension, orthostatic hypotension, and the risk of falls in a community-dwelling elderly population: the maintenance of balance, independent living, intellect and zest in the Elderly of Boston Study. J Am Geriatr Soc. 2011;59:383-9. doi:10.1111/j.1532- 5415.2011.03317.x.
61. Colon-Emeric S.C., Lee R. Dodging Complexity: cardiovascular medications and fractures. JAMA Intern Med. 2017;177(1):77-8. doi:10.1001/jamainternmed.2016.7040.
62. But D.A., Mamdani M., Austin P.C. et al. The risk of falls on initiation of antihypertensive drugs in the elderly. Osteoporosis Int. 2013;24:2649-57. doi:10.1007/s00198-013-2369-7.
63. But D.A., Mamdani M., Austin P.C. et al. The risk of hip fractures after initiating antihypertensive drugs in the elderly. Arch Intern Med. 2012;172:1739-44. doi:10.1001/2013.jamainternmed. 469.
64. Woolcott J.C., Richardson K.J., Wens M.O. et al. Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Arch Intern Med. 2009;169:1952-60. doi:10.1001/archinternmed.2009.357.