porozendoОстеопороз и остеопатииOsteoporosis and Bone Diseases2072-26802311-0716Endocrinology Research Centre10.14341/osteo2014315-21porozendo-8890Research ArticleСтатьиArticlesВОЗМОЖНОСТИ ВЛИЯНИЯ ТЕРАПИИ ВИСФОСФОНАТАМИ, А ТАКЖЕ ИХ КОМБИНАЦИИ СО СТАТИНАМИ НА ПАРАМЕТРЫ ЖЕСТКОСТИ АОРТЫ У ЖЕНЩИН С ПОСТМЕНОПАУЗАЛЬНЫМ ОСТЕОПОРОЗОМTHE POSSIBLE INFLUENCE OF BISPHOSPHONATE THERAPY AND ITS COMBINATION WITH STATINS ON PARAMETERS OF AORTIC STIFFNESS IN WOMEN WITH POSTMENOPAUSAL OSTEOPOROSISБариноваИ ВBarinovaI V

м.н.с. научно-диспансерного отдела

-БланковаЗ НBlankovaZ N

к.м.н., младший научный сотрудник научно-диспансерного отдела

-АсланянН СAslanyanN S

аспирант научно-диспансерного отдела

-АгеевФ ТAgeevF T

д.м.н., профессор, научный руководитель научно-диспансерного отдела

-РябцеваО ЮRyabtsevaO Yu

врач-эндокринолог научно-диспансерного отдела

-КочетовА ГKochetovA G

д.м.н., профессор кафедры госпитальной терапии с курсом клинической лабораторной диагностики РУДН, заведующий отделом экспериментально-теоретических исследований механизмов поведения и защиты головного мозга при сосудистой патологии НИИ цереброваскулярной патологии и инсульта РНИМУ им. Н.И. Пирогова.

-МасенкоВ ПMasenkoV P

д.м.н., профессор, руководитель отдела нейрогуморальных и иммунологических исследований

-НИИ клинической кардиологии им. А.Л. Мясникова ФГБУ «РКНПК» МЗ РФРУДН; НИИ цереброваскулярной патологии и инсульта РНИМУ им. Н.И. Пирогова201415122014173№3 (2014)1521Copyright © Баринова И.В., Бланкова З.Н., Асланян Н.С., Агеев Ф.Т., Рябцева О.Ю., Кочетов А.Г., Масенко В.П., 20142014Баринова И.В., Бланкова З.Н., Асланян Н.С., Агеев Ф.Т., Рябцева О.Ю., Кочетов А.Г., Масенко В.П.Barinova I.V., Blankova Z.N., Aslanyan N.S., Ageev F.T., Ryabtseva O.Y., Kochetov A.G., Masenko V.P.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.osteo-endojournals.ru/jour/article/view/8890

В исследовании показано, что добавление статинов к комплексной терапии остеопороза у женщин в периоде постменопаузы с различным сердечно-сосудистым риском помимо ожидаемого гиполипидемического эффекта и снижения артериальной жесткости (СПВкф, -0,36 м/сек по сравнению с группой контроля, р<0,05) сопровождается дополнительным увеличением минеральной плотности костной ткани (МПК) шейки бедра (на 4,9%, по сравнению с исходными значениями, р<0,05). терапия бисфосфонатами у женщин с постменопаузальным остеопорозом и различным сердечно-сосудистым риском сопровождалась не только ожидаемым снижением уровня маркеров костного обмена и увеличением МПК (р<0,05), а также снижением центрального систолического давления (на -4,14 и -4,18 мм рт.ст. в подгруппах активной и базовой терапии по сравнению с подгруппой контроля, соответственно, все р<0,05) и тенденцией к снижению СПВкф (-0,31 м/сек, р=0,056). динамика жесткости аорты коррелировала с изменениями интенсивности костного ремоделирования (для PINP r=0,47,p=0,019, для CITP r=0,40, p=0,05), а также центрального систолического давления (r=0,52, p=0,008)

The study shows that addition of statins to osteoporotic therapy in postmenopausal women with different cardiovascular risk beside desired hypolipidemic effect and reduction of arterial stiffness also elevates BMD at femoral neck by 4,9% from the baseline (p<0.05). Bisphosphonates therapy in postmenopausal women gives additional reduction of central systolic arterial pressure of 4.1 mm Hg with the tendency to improvement in the arterial stiffness. The dynamics of aortal stiffness was correlated with changers in intensity of bone remodeling (for N-terminal propeptides of type I procollagen (P1NP) p =0.47, p=0.019; for carboxyl-terminal telopeptide of collagen type I (CITP1) p=0.40, p=0.05) as well as systolic blood pressure (r=0.52, p=0.008). Conclusions. Bisphosphonate therapy and its combination with statins may influence the on parameters of blood pressure and aortic stiffness in women with postmenopausal osteoporosis.

остеопорозбисфосфонатыстатиныжесткость артерийosteoporosisbisphosphonatesstatinsarterial stiffnessReferencesHamerman D. Osteoporosis and atherosclerosis: biological linkages and the emergence of dual-purpose therapies. QJM. 2005 Jul; 98(7): 467-84.Hamerman D. Osteoporosis and atherosclerosis: biological linkages and the emergence of dual-purpose therapies. QJM. 2005 Jul; 98(7): 467-84.Гельцер Б.И., Кочеткова Е.А., Семисотова Е.Ф. и др. Атеросклероз и остеопороз: общий взгляд на проблему. Тера-певтическийархив. 2006; № 10: 81-85.Гельцер Б.И., Кочеткова Е.А., Семисотова Е.Ф. и др. Атеросклероз и остеопороз: общий взгляд на проблему. Тера-певтическийархив. 2006; № 10: 81-85.Zhu B.Q., Sun Y.P., Sievers R.E., et al. Effects of etidronate and lovastatin on the regression of atherosclerosis in cholesterol-fed rabbits. Cardiology. 1994; 85(6): 370-7.Zhu B.Q., Sun Y.P., Sievers R.E., et al. Effects of etidronate and lovastatin on the regression of atherosclerosis in cholesterol-fed rabbits. Cardiology. 1994; 85(6): 370-7.Bevilacqua M., Dominguez L.J., Rosini S., et al. Bisphosphonates and atherosclerosis: why? Lupus. 2005; 14(9): 773-9. Review.Bevilacqua M., Dominguez L.J., Rosini S., et al. Bisphosphonates and atherosclerosis: why? Lupus. 2005; 14(9): 773-9. Review.Adami S., Braga V., Guidi G., et al. Chronic intravenous aminobisphosphonate therapy increases high-density lipoprotein cholesterol and decreases low-density lipoprotein cholesterol. J Bone Miner Res. 2000 Mar; 15(3): 599-604.Adami S., Braga V., Guidi G., et al. Chronic intravenous aminobisphosphonate therapy increases high-density lipoprotein cholesterol and decreases low-density lipoprotein cholesterol. J Bone Miner Res. 2000 Mar; 15(3): 599-604.Edwards C.J., Hart D.J., Spector T.D. Oral statins and increased bone-mineral density in postmenopausal women. Lancet. 2000 Jun 24; 355(9222): 2218-9.Edwards C.J., Hart D.J., Spector T.D. Oral statins and increased bone-mineral density in postmenopausal women. Lancet. 2000 Jun 24; 355(9222): 2218-9.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. 2003 Apr; 32(4): 427-33.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. 2003 Apr; 32(4): 427-33.Lupattelli G., Scarponi A.M., Vaudo G., Simvastatin increases bone mineral density in hypercholesterolemic postmenopausal women. Metabolism. 2004 Jun; 53(6): 744-8.Lupattelli G., Scarponi A.M., Vaudo G., Simvastatin increases bone mineral density in hypercholesterolemic postmenopausal women. Metabolism. 2004 Jun; 53(6): 744-8.Скрипникова И.А., Собченко К.Е., Косматова О.В., др. Влияние сердечно-сосудистых препаратов на костную ткань и возможность их использования для профилактики остеопороза. Рациональная фармакотерапия в кардиологии. 2012; 4: 587-594.Скрипникова И.А., Собченко К.Е., Косматова О.В., др. Влияние сердечно-сосудистых препаратов на костную ткань и возможность их использования для профилактики остеопороза. Рациональная фармакотерапия в кардиологии. 2012; 4: 587-594.Coxon F.P., Rogers M.J. The role of prenylated small GTP-binding proteins in the regulation of osteoclast function. Calcif Tissue Int. 2003 Jan; 72(1): 80-4.Coxon F.P., Rogers M.J. The role of prenylated small GTP-binding proteins in the regulation of osteoclast function. Calcif Tissue Int. 2003 Jan; 72(1): 80-4.Luckman S.P., Hughes D.E., Coxon F.P., et al. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res. 1998 Apr; 13(4): 581-9.Luckman S.P., Hughes D.E., Coxon F.P., et al. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res. 1998 Apr; 13(4): 581-9.Беневоленская Л.И. Руководство по остеопорозу. М.: Бином, 2003.Беневоленская Л.И. Руководство по остеопорозу. М.: Бином, 2003.Mundy G., Garrett R., Harris S., et al. Stimulation of bone formation in vitro and in rodents by statins. Science. 1999 Dec 3; 286(5446): 1946-9.Mundy G., Garrett R., Harris S., et al. Stimulation of bone formation in vitro and in rodents by statins. Science. 1999 Dec 3; 286(5446): 1946-9.Laurent S., Boutouyrie P., Asmar R., et al. A. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001 May; 37(5): 1236-41.Laurent S., Boutouyrie P., Asmar R., et al. A. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001 May; 37(5): 1236-41.Cruickshank K., Riste L., Anderson S.G., et al. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Circulation. 2002 Oct 15; 106 (16): 2085-90.Cruickshank K., Riste L., Anderson S.G., et al. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Circulation. 2002 Oct 15; 106 (16): 2085-90.Guerin A.P., Blacher J., Pannier B. Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure. Circulation. 2001 Feb 20; 103(7): 987-92.Guerin A.P., Blacher J., Pannier B. Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure. Circulation. 2001 Feb 20; 103(7): 987-92.Kontopoulos A.G., Athyros V.G., Pehlivanidis A.N., Long-term treatment effect of atorvastatin on aortic stiffness in hypercholesterolaemic patients. Curr Med Res Opin. 2003; 19(1): 22-7.Kontopoulos A.G., Athyros V.G., Pehlivanidis A.N., Long-term treatment effect of atorvastatin on aortic stiffness in hypercholesterolaemic patients. Curr Med Res Opin. 2003; 19(1): 22-7.Matsuo T., Iwade K., Hirata N., Improvement of arterial stiffness by the antioxidant and anti-inflammatory effects of shortterm statin therapy in patients with hypercholesterolemia. Heart Vessels. 2005 Feb; 20(1): 8-12.Matsuo T., Iwade K., Hirata N., Improvement of arterial stiffness by the antioxidant and anti-inflammatory effects of shortterm statin therapy in patients with hypercholesterolemia. Heart Vessels. 2005 Feb; 20(1): 8-12.Mäki-Petäjä K.M., Booth A.D., Hall F.C. Ezetimibe and simvastatin reduce inflammation, disease activity, and aortic stiffness and improve endothelial function in rheumatoid arthritis. J Am CollCardiol. 2007 Aug 28; 50(9): 852-8.Mäki-Petäjä K.M., Booth A.D., Hall F.C. Ezetimibe and simvastatin reduce inflammation, disease activity, and aortic stiffness and improve endothelial function in rheumatoid arthritis. J Am CollCardiol. 2007 Aug 28; 50(9): 852-8.Hongo M., Tsutsui H., Mawatari E., et al. Fluvastatin improves arterial stiffness in patients with coronary artery disease and hyperlipidemia: a 5-year follow-up study. Circ J. 2008 May; 72(5): 722-8.Hongo M., Tsutsui H., Mawatari E., et al. Fluvastatin improves arterial stiffness in patients with coronary artery disease and hyperlipidemia: a 5-year follow-up study. Circ J. 2008 May; 72(5): 722-8.Luckish A., Cernes R., Boaz M., et al. Effect of long-term treatment with risedronate on arterial compliance in osteoporotic patients with cardiovascular risk fac-tors. Bone. 2008 Aug; 43(2): 279-83.Luckish A., Cernes R., Boaz M., et al. Effect of long-term treatment with risedronate on arterial compliance in osteoporotic patients with cardiovascular risk fac-tors. Bone. 2008 Aug; 43(2): 279-83.Toussaint N.D., Lau K.K., Strauss B.J. Effect of alendronate on vascular calcification in CKD stages 3 and 4: a pilot randomized controlled trial. Am J Kidney Dis. 2010 Jul; 56(1): 57-68.Toussaint N.D., Lau K.K., Strauss B.J. Effect of alendronate on vascular calcification in CKD stages 3 and 4: a pilot randomized controlled trial. Am J Kidney Dis. 2010 Jul; 56(1): 57-68.Kawahara T., Nishikawa M., Kawahara C., et al. Atorvastatin, etidronate, or both in patients at high risk for atherosclerotic aortic plaques: a randomized, controlled trial. Circulation. 2013 Jun 11; 127(23): 2327-35.Kawahara T., Nishikawa M., Kawahara C., et al. Atorvastatin, etidronate, or both in patients at high risk for atherosclerotic aortic plaques: a randomized, controlled trial. Circulation. 2013 Jun 11; 127(23): 2327-35.Tanriverdi H.A., Barut A., Sarikaya S. Statins have additive effects to vertebral bone mineral density in combination with risedronate in hypercholesterolemic postmenopausal women. Eur J Obstet Gynecol Reprod Biol. 2005 May 1; 120(1): 63-8.Tanriverdi H.A., Barut A., Sarikaya S. Statins have additive effects to vertebral bone mineral density in combination with risedronate in hypercholesterolemic postmenopausal women. Eur J Obstet Gynecol Reprod Biol. 2005 May 1; 120(1): 63-8.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. 2003 Apr; 32(4): 427-33.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. 2003 Apr; 32(4): 427-33.Bone H.G., Kiel D.P., Lindsay R.S., et al. Effects of atorvastatin on bone in postmenopausal women with dyslipidemia: a double-blind, placebo-controlled, dose-ranging trial. J Clin Endocrinol Metab. 2007 Dec; 92(12): 4671-7.Bone H.G., Kiel D.P., Lindsay R.S., et al. Effects of atorvastatin on bone in postmenopausal women with dyslipidemia: a double-blind, placebo-controlled, dose-ranging trial. J Clin Endocrinol Metab. 2007 Dec; 92(12): 4671-7.Stein E.A., Farnier M., Waldstreicher J., et al. Simvastatin/Atorvastatin Study Group. Effects of statins on biomarkers of bone metabolism: a randomised trial. NutrMetabCardiovasc Dis. 2001 Apr; 11(2): 84-7.Stein E.A., Farnier M., Waldstreicher J., et al. Simvastatin/Atorvastatin Study Group. Effects of statins on biomarkers of bone metabolism: a randomised trial. NutrMetabCardiovasc Dis. 2001 Apr; 11(2): 84-7.Чазова И.Е., Ратова Л.Г., Бойцов С.А., Небиеридзе Д.В. диагностика и лечение артериальной гипертензии (Рекомендации Российского медицинского общества по артериальной гипертонии и Всероссийского научного общества кардиологов). Системные гипертензии. 2010; 3: 5-26.Чазова И.Е., Ратова Л.Г., Бойцов С.А., Небиеридзе Д.В. диагностика и лечение артериальной гипертензии (Рекомендации Российского медицинского общества по артериальной гипертонии и Всероссийского научного общества кардиологов). Системные гипертензии. 2010; 3: 5-26.Лесняк О.М., Беневоленская Л.И. Остеопороз. диагностика, профилактика, лечение. м.: Геотар-Медиа, 2009.Лесняк О.М., Беневоленская Л.И. Остеопороз. диагностика, профилактика, лечение. м.: Геотар-Медиа, 2009.Ridker P.M., Danielson E., Fonseca F.A., et al. JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov 20; 359(21): 2195-207.Ridker P.M., Danielson E., Fonseca F.A., et al. JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov 20; 359(21): 2195-207.Taylor F., Ward K., Moore T.H., et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2011; CD004816.Taylor F., Ward K., Moore T.H., et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2011; CD004816.Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383-1389.Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383-1389.Shepherd J., Cobbe S.M., Ford I., et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995; 333: 1301-1307.Shepherd J., Cobbe S.M., Ford I., et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995; 333: 1301-1307.LIPID study group. Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Titles (a) Design features and baseline characteristics of the LIPID (Long-term Intervention with Pravastatin in Ischemic Disease) study: a randomized trial in patients with previous acute myocardial infarction and/or unstable angina pectoris. (b) Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. References (a) Am J Cardiol 1995; 76: 474-9. (b) N Engl J Med 1998; 339: 1349-57.LIPID study group. Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Titles (a) Design features and baseline characteristics of the LIPID (Long-term Intervention with Pravastatin in Ischemic Disease) study: a randomized trial in patients with previous acute myocardial infarction and/or unstable angina pectoris. (b) Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. References (a) Am J Cardiol 1995; 76: 474-9. (b) N Engl J Med 1998; 339: 1349-57.Lewis S.J., Moye L.A., Sacks F.M., et al. Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range. Results of the Cholesterol and Recurrent Events (CARE) trial. Ann Intern Med 1998; 129: 681-689.Lewis S.J., Moye L.A., Sacks F.M., et al. Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range. Results of the Cholesterol and Recurrent Events (CARE) trial. Ann Intern Med 1998; 129: 681-689.Reiner Zetal. Рекомендации Европейского общества кардиологов и Европейского общества атеросклероза по лечению дислипидемий. Рациональная фармакотерапия в кардиологии. 2012, приложение № 1.Reiner Zetal. Рекомендации Европейского общества кардиологов и Европейского общества атеросклероза по лечению дислипидемий. Рациональная фармакотерапия в кардиологии. 2012, приложение № 1.Yue J., Zhang X., Dong B., et al. Statins and bone health in postmenopausal women: a systematic review of randomized controlled trials. Menopause. 2010 Sep-Oct; 17(5): 1071-9.Yue J., Zhang X., Dong B., et al. Statins and bone health in postmenopausal women: a systematic review of randomized controlled trials. Menopause. 2010 Sep-Oct; 17(5): 1071-9.Rejnmark L., Buus N.H., Vestergaard P. Effects of simvastatin on bone turnover and BMD: a 1-year randomized controlled trial in postmenopausal osteopenic women. J Bone Miner Res. 2004 May; 19(5): 737-44.Rejnmark L., Buus N.H., Vestergaard P. Effects of simvastatin on bone turnover and BMD: a 1-year randomized controlled trial in postmenopausal osteopenic women. J Bone Miner Res. 2004 May; 19(5): 737-44.Athyros V.G., Mikhailidis D.P., Papageorgiou A.A., et al. The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease. A subgroup analysis of the Greek atorvastatin and coronary heart disease evaluation (GREACE) study. J ClinPathol. 2004 Jul; 57(7): 728-34.Athyros V.G., Mikhailidis D.P., Papageorgiou A.A., et al. The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease. A subgroup analysis of the Greek atorvastatin and coronary heart disease evaluation (GREACE) study. J ClinPathol. 2004 Jul; 57(7): 728-34.Shepherd J., Kastelein J.J., Bittner V., et al. Effect of intensive lipid lowering with atorvastatin on renal function in patients with coronary heart disease: the Treating to New Targets (TNT) study. Clin J Am SocNephrol. 2007 Nov; 2(6): 1131-9.Shepherd J., Kastelein J.J., Bittner V., et al. Effect of intensive lipid lowering with atorvastatin on renal function in patients with coronary heart disease: the Treating to New Targets (TNT) study. Clin J Am SocNephrol. 2007 Nov; 2(6): 1131-9.Ершова О.Б., Белова К.Ю., Назарова А.В. Фармакотерапия остеопороза. применение препарата Тевабон [Электронный ресурс]. Русский медицинский журнал, № 25, 2011, http://www.rmj.ru/articles_7936.htm [дата обращения 10.12.2014].Ершова О.Б., Белова К.Ю., Назарова А.В. Фармакотерапия остеопороза. применение препарата Тевабон [Электронный ресурс]. Русский медицинский журнал, № 25, 2011, http://www.rmj.ru/articles_7936.htm [дата обращения 10.12.2014].Liu J., Zhu L.P., Yang X.L., et al. HMG-CoA reductase inhibitors (statins) and bone mineral density: a meta-analysis. Bone. 2013 May; 54(1): 151-6.Liu J., Zhu L.P., Yang X.L., et al. HMG-CoA reductase inhibitors (statins) and bone mineral density: a meta-analysis. Bone. 2013 May; 54(1): 151-6.Ikehira H., Furuichi Y., Kinjo M., et al. Multiple extra-bone accumulations of technetium-99m-HMDP. J Nucl Med Technol. 1999 Mar; 27(1): 41-2.Ikehira H., Furuichi Y., Kinjo M., et al. Multiple extra-bone accumulations of technetium-99m-HMDP. J Nucl Med Technol. 1999 Mar; 27(1): 41-2.Ylitalo R., Mönkkönen J., Urtti A., et al. Accumulation of bisphosphonates in the aorta and some other tissues of healthy and atherosclerotic rabbits. J Lab Clin Med. 1996 Feb; 127(2): 200-6.Ylitalo R., Mönkkönen J., Urtti A., et al. Accumulation of bisphosphonates in the aorta and some other tissues of healthy and atherosclerotic rabbits. J Lab Clin Med. 1996 Feb; 127(2): 200-6.Rogers M.J.1, Watts D.J., Russell R.G. Overview of bisphosphonates. Cancer. 1997 Oct 15; 80(8 Suppl): 1652-60.Rogers M.J.1, Watts D.J., Russell R.G. Overview of bisphosphonates. Cancer. 1997 Oct 15; 80(8 Suppl): 1652-60.Ylitalo R., Kalliovalkama J., Wu X., et al. Accumulation of bisphosphonates in human artery and their effects on human and rat arterial function in vitro. PharmacolToxicol. 1998 Sep; 83(3): 125-31.Ylitalo R., Kalliovalkama J., Wu X., et al. Accumulation of bisphosphonates in human artery and their effects on human and rat arterial function in vitro. PharmacolToxicol. 1998 Sep; 83(3): 125-31.Rosenblum I.Y., Flora L., Eisenstein R. The effect of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) on a rabbit model of athero-arteriosclerosis. Atherosclerosis. 1975 Nov-Dec; 22(3): 411-24.Rosenblum I.Y., Flora L., Eisenstein R. The effect of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) on a rabbit model of athero-arteriosclerosis. Atherosclerosis. 1975 Nov-Dec; 22(3): 411-24.Kramsch D.M., Aspen A.J., Rozler L.J. Atherosclerosis: Prevention by agents not affecting abnormal levels of blood lipids. Science. 1981 Sep 25; 213(4515): 1511-2.Kramsch D.M., Aspen A.J., Rozler L.J. Atherosclerosis: Prevention by agents not affecting abnormal levels of blood lipids. Science. 1981 Sep 25; 213(4515): 1511-2.Ylitalo R., Oksala O., Ylä-Herttuala S., et al. Effects of clodronate (dichloromethylene bisphosphonate) on the development of experimental atherosclerosis in rabbits. J Lab Clin Med. 1994 May; 123(5): 769-76.Ylitalo R., Oksala O., Ylä-Herttuala S., et al. Effects of clodronate (dichloromethylene bisphosphonate) on the development of experimental atherosclerosis in rabbits. J Lab Clin Med. 1994 May; 123(5): 769-76.Fleisch H.A., Russell R.G., Bisaz S., et al. The inhibitory effect of phosphonates on the formation of calcium phosphate crystals in vitro and on aortic and kidney calcification in vivo. Eur J Clin Invest. 1970 Mar; 1(1): 12-8.Fleisch H.A., Russell R.G., Bisaz S., et al. The inhibitory effect of phosphonates on the formation of calcium phosphate crystals in vitro and on aortic and kidney calcification in vivo. Eur J Clin Invest. 1970 Mar; 1(1): 12-8.Russell R.G., Smith R., Bishop M.C., et al. Treatment of myositis ossificansprogressiva with a diphosphonate. Lancet. 1972 Jan 1; 1(7740): 10-1.Russell R.G., Smith R., Bishop M.C., et al. Treatment of myositis ossificansprogressiva with a diphosphonate. Lancet. 1972 Jan 1; 1(7740): 10-1.Frith J.C., Mönkkönen J., Auriola S., et al. The molecular mechanism of action of the antiresorptive and antiinflammatory drug clodronate: evidence for the formation in vivo of a metabolite that inhibits bone resorption and causes osteoclast and macrophage apoptosis. Arthritis Rheum. 2001 Sep; 44(9): 2201-10.Frith J.C., Mönkkönen J., Auriola S., et al. The molecular mechanism of action of the antiresorptive and antiinflammatory drug clodronate: evidence for the formation in vivo of a metabolite that inhibits bone resorption and causes osteoclast and macrophage apoptosis. Arthritis Rheum. 2001 Sep; 44(9): 2201-10.Strazzullo P., Kerry S.M., Barbato A., et al. Do statins reduce blood pressure?: a meta-analysis of randomized, controlled trials. Hypertension. 2007 Apr; 49(4): 792-8.Strazzullo P., Kerry S.M., Barbato A., et al. Do statins reduce blood pressure?: a meta-analysis of randomized, controlled trials. Hypertension. 2007 Apr; 49(4): 792-8.Banach M., Nikfar S., Rahimi R., et al. Lipid and Blood Pressure Meta-Analysis Collaboration Group. Int J Cardiol. 2013 Oct 3; 168(3): 2816-24Banach M., Nikfar S., Rahimi R., et al. Lipid and Blood Pressure Meta-Analysis Collaboration Group. Int J Cardiol. 2013 Oct 3; 168(3): 2816-24

The authors declare that there are no conflicts of interest present.