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Bone mineral density changes among women initiating blood pressure lowering drugs: a SWAN cohort study

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Abstract

Summary

We examined the effect of blood pressure lowering drugs on BMD using data from the Study of Women’s Health Across the Nation. Thiazide users had a slower decline in BMD compared to nonusers, while decline among ACE inhibitor and beta blocker users were similar to rates in nonusers.

Introduction

Several blood pressure lowering drugs may affect bone mineral density (BMD), leading to altered fracture risk. We examined the effect of blood pressure lowering drugs on BMD using data from the Study of Women’s Health Across the Nation.

Methods

We conducted a propensity score matched cohort study. Women were initiators of ACE inhibitors (ACEi), beta-blockers (BB), or thiazide diuretics (THZD). Their annualized BMD changes during the 14 years of observation were compared with nonusers.

Results

Among the 2312 eligible women, we found 69 ACEi, 71 BB, and 74 THZD users who were matched by a propensity score with the same number of nonusers. THZD users had a slower annual percent decline in BMD compared to nonusers at the femoral neck (FN) (−0.28 % vs −0.88 %; p = 0.008) and the spine (−0.74 % vs −1.0 %; p = 0.34), albeit not statistically significant. Annual percent changes in BMD among ACEi and BB users were similar to rates in nonusers. In comparison with BB, THZD use was associated with a trend toward less annualized BMD loss at the spine (−0.35 % vs −0.60 %; p = 0.08) and a similar trend at the FN (−0.39 % vs −0.64 %; p = 0.08); in comparisons with ACEi, THZD was also associated with less loss at the FN (−0.48 % vs −0.82 %; p = 0.02), but not at the spine (−0.40 % vs −0.56 %; p = 0.23).

Conclusions

Neither ACEi nor BB was associated with improvements in BMD. THZD use was associated with less annualized loss of BMD compared with nonusers, as well as compared with ACEi and BB.

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References

  1. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Mussolino ME, Neumar RW, Nichol G, Pandey DK, Paynter NP, Reeves MJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Wong ND, Woo D, Turner MB (2014) Heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation 129:e28–e292

    Article  PubMed  Google Scholar 

  2. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ (2003) Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 42:1206–1252

    Article  CAS  PubMed  Google Scholar 

  3. Reid IR, Ames RW, Orr-Walker BJ, Clearwater JM, Horne AM, Evans MC, Murray MA, McNeil AR, Gamble GD (2000) Hydrochlorothiazide reduces loss of cortical bone in normal postmenopausal women: a randomized controlled trial. Am J Med 109:362–370

    Article  CAS  PubMed  Google Scholar 

  4. LaCroix AZ, Ott SM, Ichikawa L, Scholes D, Barlow WE (2000) Low-dose hydrochlorothiazide and preservation of bone mineral density in older adults. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 133:516–526

    Article  CAS  PubMed  Google Scholar 

  5. Shimizu H, Nakagami H, Osako MK, Nakagami F, Kunugiza Y, Tomita T, Yoshikawa H, Rakugi H, Ogihara T, Morishita R (2009) Prevention of osteoporosis by angiotensin-converting enzyme inhibitor in spontaneous hypertensive rats. Hypertens Res 32:786–790

    Article  CAS  PubMed  Google Scholar 

  6. 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 38:584–588

    Article  CAS  PubMed  Google Scholar 

  7. Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, Armstrong D, Ducy P, Karsenty G (2002) Leptin regulates bone formation via the sympathetic nervous system. Cell 111:305–317

    Article  CAS  PubMed  Google Scholar 

  8. Yang S, Nguyen ND, Center JR, Eisman JA, Nguyen TV (2011) Association between beta-blocker use and fracture risk: the Dubbo Osteoporosis Epidemiology Study. Bone 48:451–455

    Article  CAS  PubMed  Google Scholar 

  9. Bonnet N, Gadois C, McCloskey E, Lemineur G, Lespessailles E, Courteix D, Benhamou CL (2007) Protective effect of beta blockers in postmenopausal women: influence on fractures, bone density, micro and macroarchitecture. Bone 40:1209–1216

    Article  CAS  PubMed  Google Scholar 

  10. Turker S, Karatosun V, Gunal I (2006) Beta-blockers increase bone mineral density. Clin Orthop Relat Res 443:73–74

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  12. Reid IR, Gamble GD, Grey AB, Black DM, Ensrud KE, Browner WS, Bauer DC (2005) beta-Blocker use, BMD, and fractures in the study of osteoporotic fractures. J Bone Miner Res 20:613–618

    Article  CAS  PubMed  Google Scholar 

  13. Perez-Castrillon JL, Vega G, Abad L, Sanz A, Mendo M, Porrero MG, Duenas A (2007) Effect of beta-blockers on bone mass and biomechanical parameters of the femoral neck in males with acute myocardial infarction. Joint Bone Spine 74:259–262

    Article  CAS  PubMed  Google Scholar 

  14. Sowers MF, Crawford S, Sternfeld B, Morganstein D, Gold EB, Greendale GA, Evans D, Neer RM, Mattews K, Sherman S, Lo A, Weiss G, Kelsey JL (2000) Design, survey, sampling and recruitment methods of SWAN: a multi-center, multi-ethnic, community based cohort study of women and the menopausal transition. In: Lobo RAKJ, Marcus M (eds) Menopause: biology and pathobiology. Academic Press, San Diego, pp 175–188

    Chapter  Google Scholar 

  15. Sherbourne CD, Stewart AL (1991) The MOS social support survey. Soc Sci Med (1982) 32:705–714

    Article  CAS  Google Scholar 

  16. Baecke JA, Burema J, Frijters JE (1982) A short questionnaire for the measurement of habitual physical activity in epidemiological studies. Am J Clin Nutr 36:936–942

    CAS  PubMed  Google Scholar 

  17. Sternfeld B, Ainsworth BE, Quesenberry CP (1999) Physical activity patterns in a diverse population of women. Prev Med 28:313–323

    Article  CAS  PubMed  Google Scholar 

  18. Rubin DB (1997) Estimating causal effects from large data sets using propensity scores. Ann Intern Med 127:757–763

    Article  CAS  PubMed  Google Scholar 

  19. Austin PC (2009) Some methods of propensity-score matching had superior performance to others: results of an empirical investigation and Monte Carlo simulations. Biom J 51:171–184

    Article  PubMed  Google Scholar 

  20. Parsons LS Reducing bias in a propensity score matched-pair sample using greedy matching techniques. In. SAS

  21. Solomon DH, Diem SJ, Ruppert K, Lian YJ, Liu CC, Wohlfart A, Greendale GA, Finkelstein JS (2015) Bone mineral density changes among women initiating proton pump inhibitors or H2 receptor antagonists: a SWAN cohort study. J Bone Miner Res 30:232–239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hernan MA, Alonso A, Logan R, Grodstein F, Michels KB, Willett WC, Manson JE, Robins JM (2008) Observational studies analyzed like randomized experiments: an application to postmenopausal hormone therapy and coronary heart disease. Epidemiology 19:766–779

    Article  PubMed  PubMed Central  Google Scholar 

  23. Liu YY, Yao WM, Wu T, Xu BL, Chen F, Cui L (2011) Captopril improves osteopenia in ovariectomized rats and promotes bone formation in osteoblasts. J Bone Miner Metab 29:149–158

    Article  PubMed  Google Scholar 

  24. Perez-Castrillon JL, Silva J, Justo I, Sanz A, Martin-Luquero M, Igea R, Escudero P, Pueyo C, Diaz C, Hernandez G, Duenas A (2003) Effect of quinapril, quinapril-hydrochlorothiazide, and enalapril on the bone mass of hypertensive subjects: relationship with angiotensin converting enzyme polymorphisms. Am J Hypertens 16:453–459

    Article  CAS  PubMed  Google Scholar 

  25. 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 57:17–25

    PubMed  Google Scholar 

  26. Kwok T, Leung J, Zhang YF, Bauer D, Ensrud KE, Barrett-Connor E, Leung PC (2012) Does the use of ACE inhibitors or angiotensin receptor blockers affect bone loss in older men? Osteoporos Int 23:2159–2167

    Article  CAS  PubMed  Google Scholar 

  27. Ray WA (2003) Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol 158:915–920

    Article  PubMed  Google Scholar 

  28. Austin PC, Steyerberg EW (2015) The number of subjects per variable required in linear regression analyses. J Clin Epidemiol 68:627–636

    Article  PubMed  Google Scholar 

  29. Butt DA, Mamdani M, Austin PC, Tu K, Gomes T, Glazier RH (2013) The risk of falls on initiation of antihypertensive drugs in the elderly. Osteoporos Int 24:2649–2657

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank the study staff at each site and all the women who participated in SWAN.

Author information

Authors and Affiliations

  1. Division of Rheumatology, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02115, USA

    D. H. Solomon, Y. J. Lian & I.-H. Kuo

  2. Division of Pharmacoepidemiology, Brigham and Women’s Hospital, Boston, MA, USA

    D. H. Solomon

  3. Department of Medicine and Division of Epidemiology & Community Health, Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA

    K. Ruppert & Z. Zhao

  4. Department of Medicine, University of California – Los Angeles, Los Angeles, CA, USA

    G. A. Greendale

  5. Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA

    J. S. Finkelstein

Authors
  1. D. H. Solomon
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  2. K. Ruppert
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  3. Z. Zhao
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  4. Y. J. Lian
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  5. I.-H. Kuo
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  6. G. A. Greendale
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  7. J. S. Finkelstein
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Corresponding author

Correspondence to D. H. Solomon.

Ethics declarations

Clinical centers

University of Michigan, Ann Arbor – Siobán Harlow, PI 2011 – present, MaryFran Sowers, PI 1994–2011; Massachusetts General Hospital, Boston, MA – Joel Finkelstein, PI 1999 – present; Robert Neer, PI 1994 – 1999; Rush University, Rush University Medical Center, Chicago, IL – Howard Kravitz, PI 2009 – present; Lynda Powell, PI 1994 – 2009; University of California, Davis/Kaiser – Ellen Gold, PI; University of California, Los Angeles – Gail Greendale, PI; Albert Einstein College of Medicine, Bronx, NY – Carol Derby, PI 2011 – present, Rachel Wildman, PI 2010 – 2011; Nanette Santoro, PI 2004 – 2010; University of Medicine and Dentistry – New Jersey Medical School, Newark – Gerson Weiss, PI 1994 – 2004; and the University of Pittsburgh, Pittsburgh, PA – Karen Matthews, PI.

NIH program office

National Institute on Aging, Bethesda, MD – Winifred Rossi 2012 - present; Sherry Sherman 1994 – 2012; Marcia Ory 1994 – 2001; National Institute of Nursing Research, Bethesda, MD – Program Officers.

Coordinating center

University of Pittsburgh, Pittsburgh, PA – Maria Mori Brooks, PI 2012 - present; Kim Sutton-Tyrrell, PI 2001 – 2012; New England Research Institutes, Watertown, MA - Sonja McKinlay, PI 1995 – 2001.

Steering committee

Susan Johnson (Current Chair), Chris Gallagher (Former Chair)

Statistical analysis

Kristine Ruppert and YinJuan Lian performed the statistical analyses and are independent of any commercial funder. They had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analyses.

Source of funding

The Study of Women’s Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), and the NIH Office of Research on Women’s Health (ORWH) (Grants NR004061; AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495). The funding agencies had no direct role in the design or conduct of the study, the collection, management, analyses, and interpretation of the data, or preparation or approval of the manuscript.

Conflicts of interest

DHS receives salary support through grants to his institution from Amgen, Lilly, Pfizer, and CORRONA. He serves in unpaid roles on trials sponsored by Lilly and Pfizer and as an unpaid member of the Governing Board of the National Bone Health Alliance. Kris Ruppert, Zhenping Zhao, YinJuan Lian, I-Hsin Kuo, Gail Greendale, and Joel Finkelstein declare that they have no conflict of interest.

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Solomon, D.H., Ruppert, K., Zhao, Z. et al. Bone mineral density changes among women initiating blood pressure lowering drugs: a SWAN cohort study. Osteoporos Int 27, 1181–1189 (2016). https://doi.org/10.1007/s00198-015-3332-6

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  • DOI: https://doi.org/10.1007/s00198-015-3332-6

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