Skip to main content
Top
Published in: Osteoporosis International 10/2019

01-10-2019 | Osteoporosis | Original Article

The renin-angiotensin aldosterone system and osteoporosis: findings from the Women’s Health Initiative

Authors: L.D. Carbone, S. Vasan, R.L. Prentice, G. Harshfield, B. Haring, J.A. Cauley, K.C. Johnson

Published in: Osteoporosis International | Issue 10/2019

Login to get access

Abstract

Summary

New users of RAAS inhibitors, including ACE inhibitors and ARBs, have a small increased risk for fracture in the first 3 years of use, with a reduced risk of fracture with longer duration of use.

Introduction

Pharmacological inhibitors of the renin-angiotensin aldosterone system (RAAS) are used to treat hypertension. However, the relationship of these medications to osteoporosis is inconsistent, and no study has included simultaneous measurements of both incident fractures and bone mineral density (BMD).

Methods

The association of RAAS inhibitor use (n = 131,793) with incident fractures in new users of these medications in women in the Women’s Health Initiative over a minimum median follow-up of 6.5 years was assessed by Cox proportional hazard models. The association of incident fractures by a cumulative duration of use of these medications (< 3 years.) and (> 3 years.) was also estimated. Subgroup analysis of fracture risk by RAAS inhibitor use confined to women with hypertension was also performed (n = 33,820). The association of RAAS inhibitor use with changes in BMD of the hip was estimated by linear regression in 8940 women with dual energy X-ray absorptiometry measurements.

Results

There was no significant association between RAAS inhibitor use and all fractures in the final adjusted multivariable models including hip BMD (HR 0.86 (0.59, 1.24)). However, among users of RAAS inhibitors, including ACE inhibitors and angiotensin receptor blockers (ARBs), hazard ratios for all incident fracture sites in final multivariable models including hip BMD showed dramatic differences by duration of use, with short duration of use (3 years or less) associated with a marked increased risk for fracture (HR 3.28 (1.66, 6.48)) to (HR 6.23 (3.11, 12.46)) and use for more than 3 years associated with a reduced fracture risk (HR 0.40 (0.24, 0.68) to (HR 0.44 (0.20, 0.97)) . Findings were similar in the subgroup of women with a history of hypertension. There was no significant change in BMD of the hip by RAAS inhibitor use.

Conclusions

In postmenopausal women, use of RAAS inhibitors, including ACE inhibitors and ARBs, is associated with an increased risk for fracture among new users of these medications in the first 3 years of use. However, long-term use (> 3 years) is associated with a reduced risk. Consideration for fracture risk may be part of the decision-making process for initiation of these medications for other disease states.
Literature
1.
go back to reference Melton LJ 3rd, Chrischilles EA, Cooper C, Lane AW, Riggs BL (1992) Perspective. How many women have osteoporosis? J Bone Miner Res Off J Am Soc Bone Miner Res 7(9):1005–1010CrossRef Melton LJ 3rd, Chrischilles EA, Cooper C, Lane AW, Riggs BL (1992) Perspective. How many women have osteoporosis? J Bone Miner Res Off J Am Soc Bone Miner Res 7(9):1005–1010CrossRef
2.
go back to reference Kanis JA, Johnell O, Oden A, Sembo I, Redlund-Johnell I, Dawson A et al (2000) Long-term risk of osteoporotic fracture in Malmo. Osteoporosis Int 11(8):669–674CrossRef Kanis JA, Johnell O, Oden A, Sembo I, Redlund-Johnell I, Dawson A et al (2000) Long-term risk of osteoporotic fracture in Malmo. Osteoporosis Int 11(8):669–674CrossRef
3.
go back to reference Cooper C, Atkinson EJ, Jacobsen SJ, O'Fallon WM, Melton LJ 3rd (1993) Population-based study of survival after osteoporotic fractures. Am J Epidemiol 137(9):1001–1005PubMedCrossRef Cooper C, Atkinson EJ, Jacobsen SJ, O'Fallon WM, Melton LJ 3rd (1993) Population-based study of survival after osteoporotic fractures. Am J Epidemiol 137(9):1001–1005PubMedCrossRef
4.
go back to reference Leibson CL, Tosteson AN, Gabriel SE, Ransom JE, Melton LJ (2002) Mortality, disability, and nursing home use for persons with and without hip fracture: a population-based study. J Am Geriatr Soc 50(10):1644–1650PubMedCrossRef Leibson CL, Tosteson AN, Gabriel SE, Ransom JE, Melton LJ (2002) Mortality, disability, and nursing home use for persons with and without hip fracture: a population-based study. J Am Geriatr Soc 50(10):1644–1650PubMedCrossRef
6.
go back to reference Carbone L, Buzkova P, Fink HA, Lee JS, Chen Z, Ahmed A, Parashar S, Robbins JR (2010) Hip fractures and heart failure: findings from the cardiovascular health study. Eur Heart J 31(1):77–84PubMedCrossRef Carbone L, Buzkova P, Fink HA, Lee JS, Chen Z, Ahmed A, Parashar S, Robbins JR (2010) Hip fractures and heart failure: findings from the cardiovascular health study. Eur Heart J 31(1):77–84PubMedCrossRef
7.
go back to reference Baldini V, Mastropasqua M, Francucci CM, D'Erasmo E (2005) Cardiovascular disease and osteoporosis. J Endocrinol Investig 28(10 Suppl):69–72 Baldini V, Mastropasqua M, Francucci CM, D'Erasmo E (2005) Cardiovascular disease and osteoporosis. J Endocrinol Investig 28(10 Suppl):69–72
8.
go back to reference Harshfield GA, Dong Y, Kapuku GK, Zhu H, Hanevold CD (2009) Stress-induced sodium retention and hypertension: a review and hypothesis. Curr Hypertens Rep 11(1):29–34PubMedCrossRef Harshfield GA, Dong Y, Kapuku GK, Zhu H, Hanevold CD (2009) Stress-induced sodium retention and hypertension: a review and hypothesis. Curr Hypertens Rep 11(1):29–34PubMedCrossRef
9.
go back to reference Shimizu H, Nakagami H, Osako MK, Hanayama R, Kunugiza Y, Kizawa T, Tomita T, Yoshikawa H, Ogihara T, Morishita R (2008) Angiotensin II accelerates osteoporosis by activating osteoclasts. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 22(7):2465–2475CrossRef Shimizu H, Nakagami H, Osako MK, Hanayama R, Kunugiza Y, Kizawa T, Tomita T, Yoshikawa H, Ogihara T, Morishita R (2008) Angiotensin II accelerates osteoporosis by activating osteoclasts. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 22(7):2465–2475CrossRef
10.
go back to reference Kaneko K, Ito M, Fumoto T, Fukuhara R, Ishida J, Fukamizu A, Ikeda K (2011) Physiological function of the angiotensin AT1a receptor in bone remodeling. J Bone Miner Res Off J Am Soc Bone Miner Res 26(12):2959–2966CrossRef Kaneko K, Ito M, Fumoto T, Fukuhara R, Ishida J, Fukamizu A, Ikeda K (2011) Physiological function of the angiotensin AT1a receptor in bone remodeling. J Bone Miner Res Off J Am Soc Bone Miner Res 26(12):2959–2966CrossRef
11.
go back to reference Li Y, Shen G, Yu C, Li G, Shen J, Gong J, Xu Y (2014) Angiotensin II induces mitochondrial oxidative stress and mtDNA damage in osteoblasts by inhibiting SIRT1-FoxO3a-MnSOD pathway. Biochem Biophys Res Commun 455(1–2):113–118PubMedCrossRef Li Y, Shen G, Yu C, Li G, Shen J, Gong J, Xu Y (2014) Angiotensin II induces mitochondrial oxidative stress and mtDNA damage in osteoblasts by inhibiting SIRT1-FoxO3a-MnSOD pathway. Biochem Biophys Res Commun 455(1–2):113–118PubMedCrossRef
12.
go back to reference Zainabadi K, Liu CJ, Caldwell ALM, Guarente L (2017) SIRT1 is a positive regulator of in vivo bone mass and a therapeutic target for osteoporosis. PLoS One 12(9):e0185236PubMedPubMedCentralCrossRef Zainabadi K, Liu CJ, Caldwell ALM, Guarente L (2017) SIRT1 is a positive regulator of in vivo bone mass and a therapeutic target for osteoporosis. PLoS One 12(9):e0185236PubMedPubMedCentralCrossRef
13.
go back to reference Butt DA, Mamdani M, Gomes T, Lix L, Lu H, Tu K (2014) Risk of osteoporotic fractures with angiotensin II receptor blockers versus angiotensin-converting enzyme inhibitors in hypertensive community-dwelling elderly. J Bone Miner Res Off J Am Soc Bone Miner Res 29(11):2483–2488CrossRef Butt DA, Mamdani M, Gomes T, Lix L, Lu H, Tu K (2014) Risk of osteoporotic fractures with angiotensin II receptor blockers versus angiotensin-converting enzyme inhibitors in hypertensive community-dwelling elderly. J Bone Miner Res Off J Am Soc Bone Miner Res 29(11):2483–2488CrossRef
14.
go back to reference Lynn H, Kwok T, Wong SY, Woo J, Leung PC (2006) Angiotensin converting enzyme inhibitor use is associated with higher bone mineral density in elderly Chinese. Bone 38(4):584–588PubMedCrossRef Lynn H, Kwok T, Wong SY, Woo J, Leung PC (2006) Angiotensin converting enzyme inhibitor use is associated with higher bone mineral density in elderly Chinese. Bone 38(4):584–588PubMedCrossRef
15.
go back to reference Kwok T, Leung J, Zhang YF, Bauer D, Ensrud KE, Barrett-Connor E et al (2012) Does the use of ACE inhibitors or angiotensin receptor blockers affect bone loss in older men? Osteoporosis Int 23(8):2159–2167CrossRef Kwok T, Leung J, Zhang YF, Bauer D, Ensrud KE, Barrett-Connor E et al (2012) Does the use of ACE inhibitors or angiotensin receptor blockers affect bone loss in older men? Osteoporosis Int 23(8):2159–2167CrossRef
16.
go back to reference Zhang YF, Qin L, Leung PC, Kwok TC (2012) The effect of angiotensin-converting enzyme inhibitor use on bone loss in elderly Chinese. J Bone Miner Metab 30(6):666–673PubMedCrossRef Zhang YF, Qin L, Leung PC, Kwok TC (2012) The effect of angiotensin-converting enzyme inhibitor use on bone loss in elderly Chinese. J Bone Miner Metab 30(6):666–673PubMedCrossRef
17.
go back to reference Masunari N, Fujiwara S, Nakata Y, Furukawa K, Kasagi F (2008) Effect of angiotensin converting enzyme inhibitor and benzodiazepine intake on bone loss in older Japanese. Hiroshima J Med Sci 57(1):17–25PubMed Masunari N, Fujiwara S, Nakata Y, Furukawa K, Kasagi F (2008) Effect of angiotensin converting enzyme inhibitor and benzodiazepine intake on bone loss in older Japanese. Hiroshima J Med Sci 57(1):17–25PubMed
18.
go back to reference Solomon DH, Mogun H, Garneau K, Fischer MA (2011) Risk of fractures in older adults using antihypertensive medications. J Bone Miner Res 26(7):1561–1567PubMedCrossRef Solomon DH, Mogun H, Garneau K, Fischer MA (2011) Risk of fractures in older adults using antihypertensive medications. J Bone Miner Res 26(7):1561–1567PubMedCrossRef
19.
go back to reference Zhang Y, Wang L, Song Y, Zhao X, Wong MS, Zhang W (2016) Renin inhibitor aliskiren exerts beneficial effect on trabecular bone by regulating skeletal renin-angiotensin system and kallikrein-kinin system in ovariectomized mice. Osteoporosis Int 27(3):1083–1092CrossRef Zhang Y, Wang L, Song Y, Zhao X, Wong MS, Zhang W (2016) Renin inhibitor aliskiren exerts beneficial effect on trabecular bone by regulating skeletal renin-angiotensin system and kallikrein-kinin system in ovariectomized mice. Osteoporosis Int 27(3):1083–1092CrossRef
20.
go back to reference Carbone LD, Cross JD, Raza SH, Bush AJ, Sepanski RJ, Dhawan S, Khan BQ, Gupta M, Ahmad K, Khouzam RN, Dishmon DA, Nesheiwat JP, Hajjar MA, Chishti WA, Nasser W, Khan M, Womack CR, Cho T, Haskin AR, Weber KT (2008) Fracture risk in men with congestive heart failure risk reduction with spironolactone. J Am Coll Cardiol 52(2):135–138PubMedCrossRef Carbone LD, Cross JD, Raza SH, Bush AJ, Sepanski RJ, Dhawan S, Khan BQ, Gupta M, Ahmad K, Khouzam RN, Dishmon DA, Nesheiwat JP, Hajjar MA, Chishti WA, Nasser W, Khan M, Womack CR, Cho T, Haskin AR, Weber KT (2008) Fracture risk in men with congestive heart failure risk reduction with spironolactone. J Am Coll Cardiol 52(2):135–138PubMedCrossRef
21.
go back to reference Kwok T, Leung J, Barrett-Connor E (2017) ARB users exhibit a lower fracture incidence than ACE inhibitor users among older hypertensive men. Age Ageing 46(1):57–64PubMed Kwok T, Leung J, Barrett-Connor E (2017) ARB users exhibit a lower fracture incidence than ACE inhibitor users among older hypertensive men. Age Ageing 46(1):57–64PubMed
22.
go back to reference Hargrove JL, Golightly YM, Pate V, Casteel CH, Loehr LR, Marshall SW, Stürmer T (2017) Initiation of antihypertensive monotherapy and incident fractures among Medicare beneficiaries. Inj Epidemiol 4(1):27PubMedPubMedCentralCrossRef Hargrove JL, Golightly YM, Pate V, Casteel CH, Loehr LR, Marshall SW, Stürmer T (2017) Initiation of antihypertensive monotherapy and incident fractures among Medicare beneficiaries. Inj Epidemiol 4(1):27PubMedPubMedCentralCrossRef
23.
go back to reference Chen CI, Yeh JS, Tsao NW, Lin FY, Shih CM, Chiang KH, Kao YT, Fang YA, Tsai LW, Liu WC, Nakagami H, Morishita R, Kuo YJ, Huang CY (2017) Association between renin-angiotensin-aldosterone system blockade and future osteoporotic fracture risk in hypertensive population: a population-based cohort study in Taiwan. Medicine 96(46):e8331PubMedPubMedCentralCrossRef Chen CI, Yeh JS, Tsao NW, Lin FY, Shih CM, Chiang KH, Kao YT, Fang YA, Tsai LW, Liu WC, Nakagami H, Morishita R, Kuo YJ, Huang CY (2017) Association between renin-angiotensin-aldosterone system blockade and future osteoporotic fracture risk in hypertensive population: a population-based cohort study in Taiwan. Medicine 96(46):e8331PubMedPubMedCentralCrossRef
24.
go back to reference Kunutsor SK, Blom AW, Whitehouse MR, Kehoe PG, Laukkanen JA (2017) Renin-angiotensin system inhibitors and risk of fractures: a prospective cohort study and meta-analysis of published observational cohort studies. Eur J Epidemiol 32(11):947–959PubMedPubMedCentralCrossRef Kunutsor SK, Blom AW, Whitehouse MR, Kehoe PG, Laukkanen JA (2017) Renin-angiotensin system inhibitors and risk of fractures: a prospective cohort study and meta-analysis of published observational cohort studies. Eur J Epidemiol 32(11):947–959PubMedPubMedCentralCrossRef
25.
go back to reference Schlienger RG, Kraenzlin ME, Jick SS, Meier CR (2004) Use of beta-blockers and risk of fractures. JAMA 292(11):1326–1332PubMedCrossRef Schlienger RG, Kraenzlin ME, Jick SS, Meier CR (2004) Use of beta-blockers and risk of fractures. JAMA 292(11):1326–1332PubMedCrossRef
26.
go back to reference Rejnmark L, Vestergaard P, Mosekilde L (2006) Treatment with beta-blockers, ACE inhibitors, and calcium-channel blockers is associated with a reduced fracture risk: a nationwide case-control study. J Hypertens 24(3):581–589PubMedCrossRef Rejnmark L, Vestergaard P, Mosekilde L (2006) Treatment with beta-blockers, ACE inhibitors, and calcium-channel blockers is associated with a reduced fracture risk: a nationwide case-control study. J Hypertens 24(3):581–589PubMedCrossRef
27.
go back to reference Butt DA, Mamdani M, Austin PC, Tu K, Gomes T, Glazier RH (2012) The risk of hip fracture after initiating antihypertensive drugs in the elderly. Arch Intern Med 172(22):1739–1744PubMedCrossRef Butt DA, Mamdani M, Austin PC, Tu K, Gomes T, Glazier RH (2012) The risk of hip fracture after initiating antihypertensive drugs in the elderly. Arch Intern Med 172(22):1739–1744PubMedCrossRef
28.
go back to reference Cheng YZ, Huang ZZ, Shen ZF, Wu HY, Peng JX, Waye MM et al (2017) ACE inhibitors and the risk of fractures: a meta-analysis of observational studies. Endocrine 55(3):732–740PubMedCrossRef Cheng YZ, Huang ZZ, Shen ZF, Wu HY, Peng JX, Waye MM et al (2017) ACE inhibitors and the risk of fractures: a meta-analysis of observational studies. Endocrine 55(3):732–740PubMedCrossRef
29.
go back to reference Chen HY, Ma KY, Hsieh PL, Liou YS, Jong GP (2016) Long-term effects of antihypertensive drug use and new-onset osteoporotic fracture in elderly patients: a population-based longitudinal cohort study. Chin Med J 129(24):2907–2912PubMedPubMedCentralCrossRef Chen HY, Ma KY, Hsieh PL, Liou YS, Jong GP (2016) Long-term effects of antihypertensive drug use and new-onset osteoporotic fracture in elderly patients: a population-based longitudinal cohort study. Chin Med J 129(24):2907–2912PubMedPubMedCentralCrossRef
30.
go back to reference Choi HJ, Park C, Lee YK, Ha YC, Jang S, Shin CS (2015) Risk of fractures in subjects with antihypertensive medications: a nationwide claim study. Int J Cardiol 184:62–67PubMedCrossRef Choi HJ, Park C, Lee YK, Ha YC, Jang S, Shin CS (2015) Risk of fractures in subjects with antihypertensive medications: a nationwide claim study. Int J Cardiol 184:62–67PubMedCrossRef
31.
go back to reference Barzilay JI, Davis BR, Pressel SL, Ghosh A, Puttnam R, Margolis KL, Whelton PK (2017) The impact of antihypertensive medications on bone mineral density and fracture risk. Curr Cardiol Rep 19(9):76PubMedCrossRef Barzilay JI, Davis BR, Pressel SL, Ghosh A, Puttnam R, Margolis KL, Whelton PK (2017) The impact of antihypertensive medications on bone mineral density and fracture risk. Curr Cardiol Rep 19(9):76PubMedCrossRef
32.
go back to reference Aoki M, Kawahata H, Sotobayashi D, Yu H, Moriguchi A, Nakagami H, Ogihara T, Morishita R (2015) Effect of angiotensin II receptor blocker, olmesartan, on turnover of bone metabolism in bedridden elderly hypertensive women with disuse syndrome. Geriatr Gerontol Int 15(8):1064–1072PubMedCrossRef Aoki M, Kawahata H, Sotobayashi D, Yu H, Moriguchi A, Nakagami H, Ogihara T, Morishita R (2015) Effect of angiotensin II receptor blocker, olmesartan, on turnover of bone metabolism in bedridden elderly hypertensive women with disuse syndrome. Geriatr Gerontol Int 15(8):1064–1072PubMedCrossRef
33.
go back to reference Solomon DH, Ruppert K, Zhao Z, Lian YJ, Kuo IH, Greendale GA, Finkelstein JS (2016) Bone mineral density changes among women initiating blood pressure lowering drugs: a SWAN cohort study. Osteoporosis Int 27(3):1181–1189CrossRef Solomon DH, Ruppert K, Zhao Z, Lian YJ, Kuo IH, Greendale GA, Finkelstein JS (2016) Bone mineral density changes among women initiating blood pressure lowering drugs: a SWAN cohort study. Osteoporosis Int 27(3):1181–1189CrossRef
34.
go back to reference Hays J, Hunt JR, Hubbell FA, Anderson GL, Limacher M, Allen C, Rossouw JE (2003) The Women's Health Initiative recruitment methods and results. Ann Epidemiol 13(9 Suppl):S18–S77PubMedCrossRef Hays J, Hunt JR, Hubbell FA, Anderson GL, Limacher M, Allen C, Rossouw JE (2003) The Women's Health Initiative recruitment methods and results. Ann Epidemiol 13(9 Suppl):S18–S77PubMedCrossRef
35.
go back to reference Curb JD, McTiernan A, Heckbert SR, Kooperberg C, Stanford J, Nevitt M et al (2003) Outcomes ascertainment and adjudication methods in the Women's Health Initiative. Ann Epidemiol 13(9 Suppl):S122–S128PubMedCrossRef Curb JD, McTiernan A, Heckbert SR, Kooperberg C, Stanford J, Nevitt M et al (2003) Outcomes ascertainment and adjudication methods in the Women's Health Initiative. Ann Epidemiol 13(9 Suppl):S122–S128PubMedCrossRef
36.
go back to reference Crandall CJ, Yildiz VO, Wactawski-Wende J, Johnson KC, Chen Z, Going SB, Wright NC, Cauley JA (2015) Postmenopausal weight change and incidence of fracture: post hoc findings from Women's Health Initiative observational study and clinical trials. BMJ 350:h25PubMedPubMedCentralCrossRef Crandall CJ, Yildiz VO, Wactawski-Wende J, Johnson KC, Chen Z, Going SB, Wright NC, Cauley JA (2015) Postmenopausal weight change and incidence of fracture: post hoc findings from Women's Health Initiative observational study and clinical trials. BMJ 350:h25PubMedPubMedCentralCrossRef
37.
go back to reference Jackson RD, LaCroix AZ, Cauley JA, McGowan J (2003) The Women's Health Initiative calcium-vitamin D trial: overview and baseline characteristics of participants. Ann Epidemiol ;13(9 Suppl):S98–106PubMedCrossRef Jackson RD, LaCroix AZ, Cauley JA, McGowan J (2003) The Women's Health Initiative calcium-vitamin D trial: overview and baseline characteristics of participants. Ann Epidemiol ;13(9 Suppl):S98–106PubMedCrossRef
38.
go back to reference Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE et al (2006) Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 354(7):669–683CrossRefPubMed Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE et al (2006) Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 354(7):669–683CrossRefPubMed
39.
go back to reference Anderson GL, Manson J, Wallace R, Lund B, Hall D, Davis S, Shumaker S, Wang CY, Stein E, Prentice RL (2003) Implementation of the Women's Health Initiative study design. Ann Epidemiol 13(9 Suppl):S5–17PubMedCrossRef Anderson GL, Manson J, Wallace R, Lund B, Hall D, Davis S, Shumaker S, Wang CY, Stein E, Prentice RL (2003) Implementation of the Women's Health Initiative study design. Ann Epidemiol 13(9 Suppl):S5–17PubMedCrossRef
40.
go back to reference Hall WD, Pettinger M, Oberman A, Watts NB, Johnson KC, Paskett ED et al (2001) Risk factors for kidney stones in older women in the southern United States. Am J Med Sci 322(1):12–18PubMedCrossRef Hall WD, Pettinger M, Oberman A, Watts NB, Johnson KC, Paskett ED et al (2001) Risk factors for kidney stones in older women in the southern United States. Am J Med Sci 322(1):12–18PubMedCrossRef
41.
go back to reference Patterson RE, Kristal AR, Tinker LF, Carter RA, Bolton MP, Agurs-Collins T (1999) Measurement characteristics of the Women's Health Initiative food frequency questionnaire. Ann Epidemiol 9(3):178–187PubMedCrossRef Patterson RE, Kristal AR, Tinker LF, Carter RA, Bolton MP, Agurs-Collins T (1999) Measurement characteristics of the Women's Health Initiative food frequency questionnaire. Ann Epidemiol 9(3):178–187PubMedCrossRef
42.
go back to reference Gong Z, Aragaki AK, Chlebowski RT, Manson JE, Rohan TE, Chen C et al (2016) Diabetes, metformin and incidence of and death from invasive cancer in postmenopausal women: results from the women's health initiative. Int J Cancer 138(8):1915–1927PubMedCrossRef Gong Z, Aragaki AK, Chlebowski RT, Manson JE, Rohan TE, Chen C et al (2016) Diabetes, metformin and incidence of and death from invasive cancer in postmenopausal women: results from the women's health initiative. Int J Cancer 138(8):1915–1927PubMedCrossRef
44.
go back to reference Wang Z, White DL, Hoogeveen R, Chen L, Whitsel EA, Richardson PA, Virani S, Garcia J, el-Serag H, Jiao L Anti-hypertensive medication use, soluble receptor for glycation end products and risk of pancreatic cancer in the Women's Health Initiative study. J Clin Med 2018;7(8)PubMedCentralCrossRef Wang Z, White DL, Hoogeveen R, Chen L, Whitsel EA, Richardson PA, Virani S, Garcia J, el-Serag H, Jiao L Anti-hypertensive medication use, soluble receptor for glycation end products and risk of pancreatic cancer in the Women's Health Initiative study. J Clin Med 2018;7(8)PubMedCentralCrossRef
45.
go back to reference Sink KM, Evans GW, Shorr RI, Bates JT, Berlowitz D, Conroy MB, Felton DM, Gure T, Johnson KC, Kitzman D, Lyles MF, Servilla K, Supiano MA, Whittle J, Wiggers A, Fine LJ (2018) Syncope, hypotension, and falls in the treatment of hypertension: results from the randomized clinical systolic blood pressure intervention trial. J Am Geriatr Soc 66(4):679–686PubMedCrossRefPubMedCentral Sink KM, Evans GW, Shorr RI, Bates JT, Berlowitz D, Conroy MB, Felton DM, Gure T, Johnson KC, Kitzman D, Lyles MF, Servilla K, Supiano MA, Whittle J, Wiggers A, Fine LJ (2018) Syncope, hypotension, and falls in the treatment of hypertension: results from the randomized clinical systolic blood pressure intervention trial. J Am Geriatr Soc 66(4):679–686PubMedCrossRefPubMedCentral
46.
go back to reference Moreland JD, Richardson JA, Goldsmith CH, Clase CM (2004) Muscle weakness and falls in older adults: a systematic review and meta-analysis. J Am Geriatr Soc 52(7):1121–1129PubMedCrossRef Moreland JD, Richardson JA, Goldsmith CH, Clase CM (2004) Muscle weakness and falls in older adults: a systematic review and meta-analysis. J Am Geriatr Soc 52(7):1121–1129PubMedCrossRef
47.
go back to reference Mertens B, Vanderheyden P, Michotte Y, Sarre S (2010) The role of the central renin-angiotensin system in Parkinson's disease. J Renin Angiotensin Aldosterone Syst 11(1):49–56PubMedCrossRef Mertens B, Vanderheyden P, Michotte Y, Sarre S (2010) The role of the central renin-angiotensin system in Parkinson's disease. J Renin Angiotensin Aldosterone Syst 11(1):49–56PubMedCrossRef
48.
go back to reference Onder G, Penninx BW, Balkrishnan R, Fried LP, Chaves PH, Williamson J et al (2002) Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: an observational study. Lancet 359(9310):926–930PubMedCrossRef Onder G, Penninx BW, Balkrishnan R, Fried LP, Chaves PH, Williamson J et al (2002) Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: an observational study. Lancet 359(9310):926–930PubMedCrossRef
49.
go back to reference Huges A (1992) Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Nuerusurg Psychiatry 55:181–184CrossRef Huges A (1992) Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Nuerusurg Psychiatry 55:181–184CrossRef
50.
go back to reference Hutcheon SD, Gillespie ND, Crombie IK, Struthers AD, McMurdo ME (2002) Perindopril improves six minute walking distance in older patients with left ventricular systolic dysfunction: a randomised double blind placebo controlled trial. Heart 88(4):373–377PubMedPubMedCentralCrossRef Hutcheon SD, Gillespie ND, Crombie IK, Struthers AD, McMurdo ME (2002) Perindopril improves six minute walking distance in older patients with left ventricular systolic dysfunction: a randomised double blind placebo controlled trial. Heart 88(4):373–377PubMedPubMedCentralCrossRef
51.
go back to reference Ahimastos AA, Lawler A, Reid CM, Blombery PA, Kingwell BA (2006) Brief communication: ramipril markedly improves walking ability in patients with peripheral arterial disease: a randomized trial. Ann Intern Med 144(9):660–664PubMedCrossRef Ahimastos AA, Lawler A, Reid CM, Blombery PA, Kingwell BA (2006) Brief communication: ramipril markedly improves walking ability in patients with peripheral arterial disease: a randomized trial. Ann Intern Med 144(9):660–664PubMedCrossRef
52.
go back to reference Sumukadas D, Witham MD, Struthers AD, McMurdo ME (2007) Effect of perindopril on physical function in elderly people with functional impairment: a randomized controlled trial. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 177(8):867–874PubMedCrossRef Sumukadas D, Witham MD, Struthers AD, McMurdo ME (2007) Effect of perindopril on physical function in elderly people with functional impairment: a randomized controlled trial. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 177(8):867–874PubMedCrossRef
53.
go back to reference Ruths S, Bakken MS, Ranhoff AH, Hunskaar S, Engesaeter LB, Engeland A (2015) Risk of hip fracture among older people using antihypertensive drugs: a nationwide cohort study. BMC Geriatr 15:153PubMedPubMedCentralCrossRef Ruths S, Bakken MS, Ranhoff AH, Hunskaar S, Engesaeter LB, Engeland A (2015) Risk of hip fracture among older people using antihypertensive drugs: a nationwide cohort study. BMC Geriatr 15:153PubMedPubMedCentralCrossRef
54.
go back to reference Garcia-Testal A, Monzo A, Rabanaque G, Gonzalez A, Romeu A (2006) Evolution of the bone mass of hypertense menopausal women in treatment with fosinopril. Med Clin 127(18):692–694CrossRef Garcia-Testal A, Monzo A, Rabanaque G, Gonzalez A, Romeu A (2006) Evolution of the bone mass of hypertense menopausal women in treatment with fosinopril. Med Clin 127(18):692–694CrossRef
55.
go back to reference Ray WA (2003) Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol 158(9):915–920PubMedCrossRef Ray WA (2003) Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol 158(9):915–920PubMedCrossRef
56.
go back to reference Cummings SR, Nevitt MC, Kidd S (1988) Forgetting falls. The limited accuracy of recall of falls in the elderly. J Am Geriatr Soc 36(7):613–616PubMedCrossRef Cummings SR, Nevitt MC, Kidd S (1988) Forgetting falls. The limited accuracy of recall of falls in the elderly. J Am Geriatr Soc 36(7):613–616PubMedCrossRef
57.
go back to reference Tinetti ME, Williams CS (1998) The effect of falls and fall injuries on functioning in community-dwelling older persons. J Gerontol A Biol Sci Med Sci 53(2):M112–M119PubMedCrossRef Tinetti ME, Williams CS (1998) The effect of falls and fall injuries on functioning in community-dwelling older persons. J Gerontol A Biol Sci Med Sci 53(2):M112–M119PubMedCrossRef
58.
go back to reference Davison J, Bond J, Dawson P, Steen IN, Kenny RA (2005) Patients with recurrent falls attending accident and emergency benefit from multifactorial intervention--a randomised controlled trial. Age Ageing 34(2):162–168PubMedCrossRef Davison J, Bond J, Dawson P, Steen IN, Kenny RA (2005) Patients with recurrent falls attending accident and emergency benefit from multifactorial intervention--a randomised controlled trial. Age Ageing 34(2):162–168PubMedCrossRef
59.
go back to reference Latham NK, Anderson CS, Reid IR (2003) Effects of vitamin D supplementation on strength, physical performance, and falls in older persons: a systematic review. J Am Geriatr Soc 51(9):1219–1226PubMedCrossRef Latham NK, Anderson CS, Reid IR (2003) Effects of vitamin D supplementation on strength, physical performance, and falls in older persons: a systematic review. J Am Geriatr Soc 51(9):1219–1226PubMedCrossRef
60.
go back to reference Hale WA, Delaney MJ, Cable T (1993) Accuracy of patient recall and chart documentation of falls. The Journal of the American Board of Family Practice 6(3):239–242PubMed Hale WA, Delaney MJ, Cable T (1993) Accuracy of patient recall and chart documentation of falls. The Journal of the American Board of Family Practice 6(3):239–242PubMed
61.
go back to reference Cauley JA, Hovey KM, Stone KL, Andrews CA, Barbour KE, Hale L, Jackson RD, Johnson KC, LeBlanc ES, Li W, Zaslavsky O, Ochs-Balcom H, Wactawski-Wende J, Crandall CJ (2019) Characteristics of self-reported sleep and the risk of falls and fractures: the Women's Health Initiative (WHI). JBMR 34(3):464–474CrossRef Cauley JA, Hovey KM, Stone KL, Andrews CA, Barbour KE, Hale L, Jackson RD, Johnson KC, LeBlanc ES, Li W, Zaslavsky O, Ochs-Balcom H, Wactawski-Wende J, Crandall CJ (2019) Characteristics of self-reported sleep and the risk of falls and fractures: the Women's Health Initiative (WHI). JBMR 34(3):464–474CrossRef
62.
go back to reference Cauley JA, Smagula SF, Hovey KM, Wactawski-Wende J, Andrews CA, Crandall CJ, LeBoff MS, Li W, Coday M, Sattari M, Tindle HA (2017) Optimism, cynical hostility, falls, and fractures: the Women's Health Initiative observational study (WHI-OS). J Bone Miner Res Off J Am Soc Bone Miner Res 32(2):221–229CrossRef Cauley JA, Smagula SF, Hovey KM, Wactawski-Wende J, Andrews CA, Crandall CJ, LeBoff MS, Li W, Coday M, Sattari M, Tindle HA (2017) Optimism, cynical hostility, falls, and fractures: the Women's Health Initiative observational study (WHI-OS). J Bone Miner Res Off J Am Soc Bone Miner Res 32(2):221–229CrossRef
Metadata
Title
The renin-angiotensin aldosterone system and osteoporosis: findings from the Women’s Health Initiative
Authors
L.D. Carbone
S. Vasan
R.L. Prentice
G. Harshfield
B. Haring
J.A. Cauley
K.C. Johnson
Publication date
01-10-2019
Publisher
Springer London
Published in
Osteoporosis International / Issue 10/2019
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-019-05041-3

Other articles of this Issue 10/2019

Osteoporosis International 10/2019 Go to the issue