Scientific Online Resource System

Varna Medical Forum

Arterial hypertension and bone health—a literature review

Radina Dimitrova, Georgi Todorov

Abstract

The prevalence of hypertension (AH) and osteoporosis is increasing worldwide, which is associated primarily with an increase in the proportion of people over the age of 50. A number of researchers have suggested that the two diseases share a common etiopathogenesis associated with low intake and correspondingly low serum calcium levels, vitamin D and vitamin K deficiency, and deviations in nitric oxide levels. In addition, there are additional prerequisites for the adverse effects of AH on bone tissue. It is known, for example, that higher blood pressure (BP) levels cause greater loss of calcium in the urine. On the other hand, AH is also associated with increased sympathetic tone, vascular disorders, abnormal cytokine levels, and increased activity of the renin-angiotensin-aldosterone system (RAAS) at the systemic and local levels. In addition, the number of falls, which are a leading factor in the occurrence of fractures, in patients with AH may be increased. A prerequisite for this is the presence of syncope associated with decreased baroreflex sensitivity or orthostatic hypotension caused by antihypertensive drugs. The potential link between AH and bone health has long been discussed, but the results of numerous clinical trials remain mixed. The presence of some inconsistencies in the literature may be related to differences in the stage and severity of AH among the studied populations, as well as to the control of AH. On the other hand, antihypertensive drugs, which have specific effects on different target organs, may further modulate bone homeostasis. However, not all studies clarify whether patients receive therapy for elevated AH.


Keywords

bone, osteoporosis, fractures, hypertension

Full Text


References

Yang S, Nguyen ND, Center JR, Eisman JA, Nguyen TV. Association between hypertension and fragility fracture: a longitudinal study. Osteoporos Int. 2014; 25: 97–103.

Do Carmo L, Harrison D.G. Hypertension and osteoporosis: Common pathophysiological mechanisms Medicine in Novel Technology and Devices. 2020; 8: 1000472

Harrington F, Murray A, Ford GA. Relationship of baroreflex sensitivity and blood pressure in an older population. J Hypertens. 2000; 18: 1629-23.

Sarasin FP, Louis-Simonet M, Carballo D, Slema S, Junod AP, Unger FP. Prevalence of orthostatic hypotension among patients presenting with syncope in the ED. Am J Emerg Med. 2002; 20: 497-50

Cappuccio FP, Meilahn E, Zmuda JM, Cauley JA. High blood pressure and bone-mineral loss in elderly white women: a prospective study. Study of Osteoporotic Fractures Research Group. Lancet. 1999; 354: 971.

Tsuda K, Nistui I, Masuyama Y. Bone mineral density in women with essential hypertension. Am J Hypertens 2001; 14: 704-707.

Afghani A, Johnson CA. Resting blood pressure and bone mineral content are inversely related in overweight and obese Hispanic women. Am J Hypertens. 2006; 19: 286–92.

Yazici S, Yazici M, Korkmaz U, et al. Relationship between blood pressure levels and bone mineral density in postmenopausal Turkish women. Arch Med Sci. 2011; 7(2): 264-270.

Li C, Zeng Y, Tao L, Liu S, Ni Z, Huang Q, Wang Q. Meta-analysis of hypertension and osteoporotic fracture risk in women and men. Osteoporos Int. 2017; 28: 2309–18

Ye Z., Lu H., Liu P. Association between essential hypertension and bone mineral density: a systematic review and meta-analysis. Oncotarget. 2017; 8: 68916-68927.

Maeda S, Miyaki A, Sasai H, Tsujimoto T, So R, Tanaka K. Lifestyle Modification Decreases Arterial Stiffness in Overweight and Obese Men: Dietary Modification vs. Exercise Training. Int J Sport Nutr Exerc Metab. 2015; 25: 69–77.

Hanley DA, Brown JP, Tenenhouse A, et al. Associations among disease conditions, bone mineral density and prevalent vertebral deformities in men and women 50 years of age and older: Crosssectional results from the Canadian Multicentre Osteoporosis Study. J Bone Miner Res 2003; 18: 784-780.

Javed F, Khan SA, Ayers EW, Aziz EF, Akram MS, Nadkarni GN, et al. Association of hypertension and bone mineral density in an elderly African American female population. J Natl Med Assoc. 2012; 104: 172–8.

Hijazi N, Alourfi Z. Association between Hypertension, Antihypertensive Drugs, and Osteoporosis in Postmenopausal Syrian Women: A Cross-Sectional Study. Adv Med. 2020; 2020:7014212.

Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people: a systematic review and meta-analysis: II. Cardiac and analgesic drugs. J Am Geriatr Soc 1999; 47: 40-50.

Hall TJ, Schaueblin M. Hydrochlorothiazide inhibits osteoclastic bone resorption in vitro. Calcif Tissue Int 1994; 55: 266-268.

Barry EL, Gesek FA, Kaplan MR, Hebert SC, Friedman PA. Expression of the sodium-chloride cotransporter in osteoblast-like cells: effect of thiazide diuretics. Am J Physiol 1997; 272: C109- C116.

Lajneusse D, Delalandre A, Guggino SE. Thieazide diuretics affect osteocalcin production in human osteoblasts at the transcription level without afecting vitamin D3 receptors. J Bone Miner Res 2000; 15: 894-901.

Kurokawa K. The kidney and calcium homeostasis. Kidney Int 1994; 45 ( Suppl 4 ): S97-S105.

Heidrich FE, Stergachis A, Gross KM. Diuretic drug use and the risk for hip fracture. Ann Intern Med 1991; 115: 1-6.

Wasnich R, Davis J, Ross P, Vogel J. Effect of thiazide on rates of bone mineral loss: a longitudinal study. BMJ 1990; 301: 1303-1305

Wasnich R.D, Davis J.W, He Y.F, Petrovich Н, Ross P.D. A randomized, double-masked, placebo-controlled trial of chlorthalidone and bone loss in elderly women. Osteoporos. Int. 1995; 5: 247–251

Cauley JA, Cummings SR, Seeley DG et al. Effects of thiazide diuretic therapy on bone mass, fractures and falls. The Study of Osteoporotic Fractures Research Group. Ann Intern Med 1993; 118: 666-673.

Reid IR, Ames RW, Orr-Walker B et al. Hydrochlorothiazide reduces loss of cortical bone in normal postmenopausal women: a randomised controlled trial. Am J Med 2000; 109: 362-370.

La Croix AZ, Ott S, Ichikawa L, et al. Low-dose HCTZ and preservation of bone mineral density in older adults. A randomised, double-blind, placebo-controlled trial. Ann Intern Med 2000; 133: 516-526

Sigurdsson G, Franzson L. Increased bone mineral density in a population-based group of 70-year-old women on thiazide diuretics, independent of parathyroid hormone levels. J. Intern. Med. 2001; 250: 51–56

Jones G, Nguyen T, Sambrook PN, Eisman JA. Thiazide diuretics and fractures: Can meta-analysis help ?. J Bone Miner Res 1995; 10: 106-111.

Schoofs M, Van der Klift M, Hofman A et al. Thiazide diuretic and the risk for hip fracture. Ann Intern Med 2003; 139: 476-482.

Aung K, Htay T. Thiazide diuretics and the risk of hip fracture. Cochrane Database Syst. Rev. 2011; 10: CD005185

Rejnmark L, Vestergaard P, Heickendorff L, Andreasen F, Mosekilde L. Effects of long-term treatment with loop diuretics on bone mineral density, calcitropic hormones and bone turnover. J. Intern. Med. 2005; 257: 176–184

Elmgreen J, Tougaard L, Leth A, Christensen. M.S. Elevated serum parathyroid hormone concentration during treatment with high ceiling diuretics. Eur. J. Clin. Pharmacol. 1980; 18: 363–364

Lim L.S, Fink H.A, Blackwell T, Taylor B.C, Ensrud K.E. Loop diuretic use and rates of hip bone loss and risk of falls and fractures in older women. J. Am. Geriatr. Soc. 2009; 57: 855–862.

Lim L.S, Fink H.A, Kuskowski M.A, Taylor B.C, Schousboe J.T, Ensrud K.E. Loop diuretic use and increased rates of hip bone loss in older men: the osteoporotic fractures in men study. Arch. Intern. Med. 2008: 168: 735–740

Rejnmark L, Vestergaard P, Heickendorff L, Andreasen F, Mosekilde L. 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: 163–170

Rejnmark L, Vestergaard P, Pedersen R.A, Heickendorff L, Andreasen F, Mosekilde L. Dose-effect relations of loop- and thiazide-diuretics on calcium homeostasis: a randomized, doubleblinded Latin-square multiple cross-over study in postmenopausa osteopenic women. Eur. J. Clin. Invest. 2003: 33: 41–50

Arampatzis S, Gaetcke L.M, Funk G.C, Schwarz C, Mohaupt M, Zimmermann H, et al. Diuretic-induced hyponatremia and osteoporotic fractures in patients admitted to the emergency department. Maturitas. 2013; 75: 81–86

Solomon DH, Mogun H, Garneau K, Fischer MA. Risk of fractures in older adults using antihypertensive medications. J Bone Miner Res Off J Am Soc Bone Miner Res. 2011; 26(7): 1561–7.

Law P.H, Sun Y, Bhattacharya S., Chhokar V.S, Weber K.T. Diuretics and bone loss in rats with aldosteronism. J. Am. Coll. Cardiol. 2005; 46: 142–146

Salcuni A.S, Palmieri S, Carnevale V, Morelli V, Battista C, Guarnieri V, et al. Bone involvement in aldosteronism. J. Bone Miner Res. 2012; 27: 2217–2222

Ceccoli L, Ronconi V, Giovannini L, Marcheggiani M, Turchi M, Boscaro M, et al. Bone health and aldosterone excess. Osteoporos Int. 2013; 24(11): 2801–2807

Carbone L.D, Cross J.D, Raza S.H, Bush A.J, Sepanski R.J, Dhawan S, et al. Fracture risk in men with congestive heart failure risk reduction with spironolactone. J. Am. Coll. Cardiol. 2008; 52: 135–138

Togari A. Adrenergic regulation of bone metabolism: possible involvement of sympathetic innervation of osteoblastic and osteoclastic cells. Microsc Res Tech 2002; 58: 77-84.

Takeda S, Elefteriou F Karsenty G et al. Leptin regulates bone formation via the sympathetic nervous system. Cell 2002; 111: 305- 317.

Kondo A, Togari A. In vivo stimulation of sympathetic nervous system modulates osteoblastic activity in mouse calvaria. Am J Physiol Endocrinol Metab 2003; 285: E661-667.

Hill E.L, Turner R, Elde R. Effects of neonatal sympathectomy and capsaicin treatment on bone remodeling in rats. Neuroscience 1991; 44: 747–755

Huang H.H, Brennan T.C, Muir M.M, Mason R.S. Functional alpha1- and beta2-adrenergic receptors in human osteoblasts. J. Cell. Physiol. 2009; 220: 267–275

Rodrigues W.F, Madeira M.F, da Silva T.A, Clemente-Napimoga J.T, Miguel C.B, Dias-da-Silva V.J, et al. Low dose of propranolol downmodulates bone resorption by inhibiting inflammation and osteoclast differentiation. Br. J. Pharmacol. 2012; 165: 2140–2151

Pasco JA, Henry MJ, Sanders KM, Kotowicz MA, Seeman E, Nicholson GC. b- adrenergic blockers reduce the risk of fracture partly by increasing bone mineral density: Geelong Osteoporosis Study. J Bone Miner Res 2004; 19: 19-24.

Schlienger RG, Kraenzlin ME, Jick SS, Meier CR. Use of bblockers and risk of fractures. JAMA 2004; 292: 1326-1332.

55. S. Yang, N.D. Nguyen, J.R. Center, J.A. Eisman, T.V. Nguyen, Association between beta-blocker use and fracture risk: the Dubbo Osteoporosis Epidemiology Study. Bone 48, 451–45 (2011)

56. H.J. Song, J. Lee, Y.J. Kim, S.Y. Jung, H.J. Kim, N.K. Choi, B.J. Park, b1 selectivity of b-blockers and reduced risk of fractures in elderly hypertension patients. Bone 51, 1008–1015 (2012)

Yang S, Nguyen N.D, Eisman J.A, Nguyen T.V. Association between beta-blockers and fracture risk: a Bayesian meta-analysis. Bone 2012; 51: 969–974

Toulis K.A, Hemming K, Stergianos S, Nirantharakumar K, Bilezikian J.P. b-Adrenergic receptor antagonists and fracture risk: a meta-analysis of selectivity, gender, and site-specific effects. Osteoporos Int. (2013). doi:10.1007/s00198-013-2498-z

Gradosova I, Zivna H, Palicka V, Hubena S, Svejkovska K, Zivny P. Protective effect of amlodipine on rat bone tissue after orchidectomy. Pharmacology. 2012; 89: 37–43

Ushijima K, Liu Y, Maekawa T, Ishikawa E, Motosugi Y, Ando H, et al. Protective effect of amlodipine against osteoporosis in stroke-prone spontaneously hypertensive rats. Eur. J. Pharmacol. 2010; 635: 227–230

Kosaka N, Uchii M. Effect of benidipine hydrochloride, a dihydropyridine-type calcium antagonist, on the function of mouse osteoblastic cells. Calcif. Tissue Int. 1998; 62: 554–556

Duriez J, Flautre B, Blary MC, Hardouin P. Effects of the calcium channel blocker nifedipine on epiphyseal growth plate and bone turnover: A study in rabbit. Calcif Tissue Int. 1993; 52:120–4.

Halici Z, Borekci B, Ozdemir Y, Cadirci E, Suleyman H. Protective effects of amlodipine and lacidipine on ovariectomyinduced bone loss in rats. Eur. J. Pharmacol. 2008; 579: 241–245

Albers M.M, Johnson W, Vivian V, Jackson R.D. Chronic use of the calcium channel blocker nifedipine has no significant effect on bone metabolism in men. Bone 1991; 12: 39–42

Zofkova´ I, Kancheva R.L, The effect of nifedipine on serum parathyroid hormone and calcitonin in postmenopausal women. Life Sci. 1995; 57: 1087–1096

Zacharieva S, Shigarminova R, Nachev E et al. Effect of amlodipine and hormone replacement therapy on blood pressure and bone markers in menopause. Methods Find Exp Clin Pharmacol 2003; 25: 209-213.

Ay S.A., Karaman M.,Cakar M, Balta S, Arslan E, Bulucu F, et al. Amlodipine increases vitamin D levels more than valsartan in newly diagnosed hypertensive patients: pointing to an additional effect on bone metabolism or a novel marker of inflammation? Ren. Fail. 2013; 35: 691–696

Fagher B, Hennigsen N, Hulthen L, Katzman P, Thulin T. Antihypertensive and renal effects of enalapril and slow-release verapamil in essential hypertension. Eur J Clin Pharmacol 1990 (Suppl 12): 41S-43S.

Perezcastrillon JL, Justo I, Sanzcantalapiedra A, Pueyo C, Hernandez G, Duenas A. Effect of the Antihypertensive Treatment on the Bone Mineral Density and Osteoporotic Fracture. Curr Hypertens Rev. 2005; 1:61–66.

Matta C, Zákány R, Mobasheri A. Voltage-dependent calcium channels in chondrocytes: roles in health and disease. Curr Rheumatol Rep. 2015; 17:43.

Ralston S.H, Todd D, Helfrich M, Benjamin N, Grabowski P.S. Human osteoblast-like cells produce nitric oxide and express inducible nitric oxide synthase. Endocrinology. 1994; 135: 330–336

Lo¨wik C.W, Nibbering P.H, van de Ruit M, Papapoulos S.E. Inducible production of nitric oxide in osteoblast-like cells and in fetal mouse bone explants is associated with suppression of osteoclastic bone resorption. J. Clin. Invest. 1994; 93: 1465–1472

Hukkanen M, Platts L.A, Lawes T, Girgis S.I, Konttinen Y.T, Goodship A.E, et al. Effect of nitric oxide donor nitroglycerin on bone mineral density in a rat model of estrogen deficiency-induced osteopenia. Bone. 2003; 32: 142–149

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: 1755–1759

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: 1811–1817

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: 1512–1517

Izu Y, Mizoguchi F, Kawamata A, et al. Angiotensin II type 2 receptor blockade increases bone mass. J Biol Chem. 2009; 284(8):4857–64.

Hatton R, Stimpel M, Chambers TJ. Angiotensin II is generated from angiotensin I by bone cells and stimulates osteoclastic bone resorption in vitro. J Endocrinol. 1997; 152(1): 5–10.

Hiruma Y, Inoue A, Hirose S, Hagiwara H. Angiotensin II stimulates the proliferation of osteoblast-rich populations of cells from rat calvariae. Biochem Biophys Res Commun. 1997; 230(1): 176–8.

Lamparter S, Kling L, Schrader M, Ziegler R, Pfeilschifter J. Effects of angiotensin II on bone cells in vitro. J Cell Physiol. 1998; 175(1): 89–98.

Hagiwara H, Hiruma Y, Inoue A, Yamaguchi A, Hirose S. Deceleration by angiotensin II of the differentiation and bone formation of rat calvarial osteoblastic cells. J Endocrinol. 1998;156(3):543–50.

Grant FD, Mandel SJ, Brown EM, Williams GH, Seely EW. Interrelationships between the renin-angiotensin-aldosterone and calcium homeostatic systems. J Clin Endocrinol Metab 1992; 75: 988-992.

Perez-Castrillón JL, Justo I, Silva J, et al. Relationship between bone mineral density and angiotensin converting enzyme polymorphism in hypertensive postmenopausal women. Am J Hypertens 2003; 16: 233-235.

Shimizu H, Nakagami H, Osako MK, et al. Angiotensin II accelerates osteoporosis by activating osteoclasts. FASEB J Off Publ Fed Am Soc Exp Biol. 2008; 22(7): 2465–75.

Donmez BO, Ozdemir S, Sarikanat M, et al. Effect of angiotensin II type 1 receptor blocker on osteoporotic rat femurs. Pharmacol Rep. 2012; 64(4): 878–88.

Garcia P, Schwenzer S, Slotta JE, et al. Inhibition of angiotensinconverting enzyme stimulates fracture healing and periosteal callus formation—role of a local renin-angiotensin system. Br J Pharmacol. 2010; 159(8): 1672–80.

Townsend R, DiPette DJ, Evans RR et al. Effects of calcium channel blockade on calcium homeostasis in mild to moderate essential hypertension. Am J Med Sci 1990; 300: 133-137.

Puig JC, Mateos FA, Ramos TH, Lavilla MP, Capitan MC, Gil A. Albumin excretion rate and metabolic modifications in patients with essential hipertensión. Effects of two angiotensin converting enzyme inhibitors. Am J Hypertens 1994; 7: 46-51.

Garcı´a-Testal A, Monzo´ A, Rabanaque G, Gonza´lez A, Romeu A. Evolution of the bone mass of hypertense menopausal women in treatment with fosinopril. Med. Clin. (Barc). 2006; 127: 692–694

Lynn H, Kwok T, Wong S.Y, Woo J, Leung P.C. Angiotensin converting enzyme inhibitor use is associated with higher bone mineral density in elderly Chinese. Bone. 2006; 38: 584–588

Rejnmark L, Vestergaard P, Mosekilde L. Treatment with betablockers, ACE inhibitors, and calcium-channel blockers is associated with a reduced fracture risk: a nationwide case-control study. J. Hypertens. 2006; 24: 581–589

Wiens M, Etminan M, Gill S.S, Takkouche B. Effects of antihypertensive drug treatments on fracture outcomes: a metaanalysis of observational studies. J. Intern. Med. 2006; 260: 350–362

Kwok T, Leung J, Zhang Y.F, Bauer D, Ensrud K.E, Barrett-Connor E, et al. Osteoporotic Fractures in Men (MrOS) Research Group. Does the use of ACE inhibitors or angiotensin receptor blockers affect bone loss in older men? Osteoporos. Int. 2012; 23: 2159–2167

Cheng YZ, Huang ZZ, Shen ZF, et al. ACE inhibitors and the risk of fractures: a meta-analysis of observational studies. Endocrine. 2017;55(3):732–40.

Broulik PD, Tesar V, Zima T, Jirsa M. Impact of antihypertensive therapy on the skeleton: Effects of enalapril and AT1 receptor antagonist Losartan in female rats. Physiol Res 2001; 50: 335-338.

Bayar A, Turan A, Gulle K, Akpolat M, Turan I, Turhan E. The effects of the angiotensin converting enzyme inhibitor enalapril and the angiotensin II type 1 receptor blocker Losartan on fracture healing in rats. Clin Invest Med. 2015; 38(4): E164–72.

Kunutsor S, Blom A, Whitehouse M, Kehoe P, Laukkanen J. Renin-angiotensin system inhibitors and risk of fractures: a prospective cohort study and meta-analysis of published observational cohort studies Eur J Epidemiol. 2017; 32: 947–959

Ruths S, Bakken MS, Ranhoff AH, Hunskaar S, Engesaeter LB, Engeland A. Risk of hip fracture among older people using antihypertensive drugs: a nationwide cohort study. BMC Geriatr. 2015; 15: 153.

Choi HJ, Park C, Lee YK, Ha YC, Jang S, Shin CS. Risk of fractures in subjects with antihypertensive medications: a nationwide claim study. Int J Cardiol. 2015; 184: 62–7.




DOI: http://dx.doi.org/10.14748/vmf.v0i0.7614

Refbacks

Font Size


|