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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2019

Open Access 01-12-2019 | Stroke | Research article

Association between diuretic use and the risk of vertebral fracture after stroke: a population-based retrospective cohort study

Authors: Shu-Man Lin, Shih-Hsien Yang, Chih-Yung Wang, Huei-Kai Huang

Published in: BMC Musculoskeletal Disorders | Issue 1/2019

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Abstract

Background

Stroke is a major risk factor for osteoporosis and fractures. No study has evaluated the association between diuretic use and risk of vertebral fracture in stroke patients, although a considerable proportion of stroke patients are prescribed diuretics for hypertension. Our study aimed to investigate whether treatment with thiazides or loop diuretics affects the risk of vertebral fracture after stroke.

Methods

A population-based propensity score-matched retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database. Patients with a new diagnosis of stroke between 2000 and 2011 were included. After propensity score matching, 9468 patients were included in the analysis of the effect of thiazides, of who 4734 received thiazides within 2 years after stroke. To analyze the loop diuretic effect, 4728 patients were included, of who 2364 received loop diuretics. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) of vertebral fractures among patients according to thiazide or loop diuretic use within 2 years following stroke. Sensitivity analyses based on the duration of thiazide or loop diuretic use were further conducted.

Results

There was no significant difference in vertebral fracture risk between thiazide users and non-users (adjusted HR [aHR] = 1.14, 95% confidence interval [CI] = 0.88–1.47, p = 0.316). Loop diuretic users had a significantly higher vertebral fracture risk than non-users (aHR = 1.45, 95% CI = 1.06–1.98, p = 0.019). However, the sensitivity analysis revealed that short-term thiazide use (exposure duration < 90 days within 2 years after stroke) significantly increased the risk of vertebral fracture versus non-use (aHR = 1.38, 95% CI = 1.02–1.88, p = 0.039). Only short-term loop diuretic users had significantly higher risk of vertebral fracture (aHR = 1.56, 95% CI = 1.11–2.20, p = 0.011). The other two subgroups with longer exposure duration in analyses for both thiazides and loop diuretics revealed no significant effect.

Conclusions

Short-term thiazide or loop diuretic use was associated with an increased risk of vertebral fracture after stroke. Further prospective clinical trials are required to confirm this finding.
Literature
1.
Riggs BL, Melton LJ 3rd. The worldwide problem of osteoporosis: insights afforded by epidemiology. Bone. 1995;17(5 Suppl):505S–11S.PubMedCrossRef
2.
Waterloo S, Ahmed LA, Center JR, Eisman JA, Morseth B, Nguyen ND, Nguyen T, Sogaard AJ, Emaus N. Prevalence of vertebral fractures in women and men in the population-based Tromso study. BMC Musculoskelet Disord. 2012;13:3.PubMedPubMedCentralCrossRef
3.
Hasserius R, Karlsson MK, Jonsson B, Redlund-Johnell I, Johnell O. Long-term morbidity and mortality after a clinically diagnosed vertebral fracture in the elderly--a 12- and 22-year follow-up of 257 patients. Calcif Tissue Int. 2005;76(4):235–42.PubMedCrossRef
4.
Nevitt MC, Ettinger B, Black DM, Stone K, Jamal SA, Ensrud K, Segal M, Genant HK, Cummings SR. The association of radiographically detected vertebral fractures with back pain and function: a prospective study. Ann Intern Med. 1998;128(10):793–800.PubMedCrossRef
5.
Kado DM, Browner WS, Palermo L, Nevitt MC, Genant HK, Cummings SR. Vertebral fractures and mortality in older women: a prospective study. Study of osteoporotic fractures research group. Arch Intern Med. 1999;159(11):1215–20.PubMedCrossRef
6.
Carda S, Cisari C, Invernizzi M, Bevilacqua M. Osteoporosis after stroke: a review of the causes and potential treatments. Cerebrovasc Dis. 2009;28(2):191–200.PubMedCrossRef
7.
Jorgensen L, Engstad T, Jacobsen BK. Bone mineral density in acute stroke patients: low bone mineral density may predict first stroke in women. Stroke. 2001;32(1):47–51.PubMedCrossRef
8.
Sato Y, Kuno H, Kaji M, Etoh K, Oizumi K. Influence of immobilization upon calcium metabolism in the week following hemiplegic stroke. J Neurol Sci. 2000;175(2):135–9.PubMedCrossRef
9.
Dennis MS, Lo KM, McDowall M, West T. Fractures after stroke: frequency, types, and associations. Stroke. 2002;33(3):728–34.PubMedCrossRef
10.
Kapral MK, Fang J, Alibhai SM, Cram P, Cheung AM, Casaubon LK, Prager M, Stamplecoski M, Rashkovan B, Austin PC. Risk of fractures after stroke: results from the Ontario stroke registry. Neurology. 2017;88(1):57–64.PubMedPubMedCentralCrossRef
11.
12.
Hsieh FI, Lien LM, Chen ST, Bai CH, Sun MC, Tseng HP, Chen YW, Chen CH, Jeng JS, Tsai SY, et al. Get with the guidelines-stroke performance indicators: surveillance of stroke care in the Taiwan stroke registry: get with the guidelines-stroke in Taiwan. Circulation. 2010;122(11):1116–23.PubMedCrossRef
13.
Musini VM, Nazer M, Bassett K, Wright JM. Blood pressure-lowering efficacy of monotherapy with thiazide diuretics for primary hypertension. Cochrane Database Syst Rev. 2014;5:CD003824.
14.
15.
Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA. 2002;287(3):337–44.PubMedCrossRef
16.
LaCroix AZ, Ott SM, Ichikawa L, Scholes D, Barlow WE. Low-dose hydrochlorothiazide and preservation of bone mineral density in older adults. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2000;133(7):516–26.PubMedCrossRef
17.
Dvorak MM, De Joussineau C, Carter DH, Pisitkun T, Knepper MA, Gamba G, Kemp PJ, Riccardi D. 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(9):2509–16.PubMedCrossRef
18.
Hoorn EJ, Rivadeneira F, van Meurs JB, Ziere G, Stricker BH, Hofman A, Pols HA, Zietse R, Uitterlinden AG, Zillikens MC: Mild hyponatremia as a risk factor for fractures: the Rotterdam study. J Bone Miner Res 2011, 26(8):1822–1828.
19.
Kinsella S, Moran S, Sullivan MO, Molloy MG, Eustace JA. Hyponatremia independent of osteoporosis is associated with fracture occurrence. Clin J Am Soc Nephrol. 2010;5(2):275–80.PubMedPubMedCentralCrossRef
20.
Usala RL, Fernandez SJ, Mete M, Cowen L, Shara NM, Barsony J, Verbalis JG. Hyponatremia is associated with increased osteoporosis and bone fractures in a large US health system population. J Clin Endocrinol Metab. 2015;100(8):3021–31.PubMedPubMedCentralCrossRef
21.
Jamal SA, Arampatzis S, Harrison SL, Bucur RC, Ensrud K, Orwoll ES, Bauer DC. Hyponatremia and fractures: findings from the MrOS study. J Bone Miner Res. 2015;30(6):970–5.PubMedCrossRef
22.
Friedman PA, Bushinsky DA. Diuretic effects on calcium metabolism. Semin Nephrol. 1999;19(6):551–6.PubMed
23.
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(2):176–84.PubMedCrossRef
24.
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(1):163–70.PubMedCrossRef
25.
Lim LS, Fink HA, Kuskowski MA, Taylor BC, Schousboe JT, Ensrud KE. Loop diuretic use and increased rates of hip bone loss in older men: the osteoporotic fractures in men study. Arch Intern Med. 2008;168(7):735–40.PubMedCrossRef
26.
Okada K, Okada M, Kamada N, Yamaguchi Y, Kakehashi M, Sasaki H, Katoh S, Morita K. Reduction of diuretics and analysis of water and muscle volumes to prevent falls and fall-related fractures in older adults. Geriatr Gerontol Int. 2017;17(2):262–9.
27.
Aung K, Htay T. Thiazide diuretics and the risk of hip fracture. Cochrane Database Syst Rev. 2011;10:CD005185.
28.
Puttnam R, Davis BR, Pressel SL, Whelton PK, Cushman WC, Louis GT, Margolis KL, Oparil S, Williamson J, Ghosh A, et al. Association of 3 different antihypertensive medications with hip and pelvic fracture risk in older adults: secondary analysis of a randomized clinical trial. JAMA Intern Med. 2017;177(1):67–76.PubMedCrossRef
29.
Corrao G, Mazzola P, Monzio Compagnoni M, Rea F, Merlino L, Annoni G, Mancia G. Antihypertensive Medications, Loop Diuretics, and Risk of hip fracture in the elderly: a population-based cohort study of 81,617 Italian patients newly treated between 2005 and 2009. Drugs Aging. 2015;32(11):927–36.PubMedCrossRef
30.
Berry SD, Zhu Y, Choi H, Kiel DP, Zhang Y. Diuretic initiation and the acute risk of hip fracture. Osteoporos Int. 2013;24(2):689–95.PubMedCrossRef
31.
Schoofs MW, van der Klift M, Hofman A, de Laet CE, Herings RM, Stijnen T, Pols HA, Stricker BH. Thiazide diuretics and the risk for hip fracture. Ann Intern Med. 2003;139(6):476–82.PubMedCrossRef
32.
LaCroix AZ, Wienpahl J, White LR, Wallace RB, Scherr PA, George LK, Cornoni-Huntley J, Ostfeld AM. Thiazide diuretic agents and the incidence of hip fracture. N Engl J Med. 1990;322(5):286–90.PubMedCrossRef
33.
Nevitt MC, Cummings SR, Stone KL, Palermo L, Black DM, Bauer DC, Genant HK, Hochberg MC, Ensrud KE, Hillier TA, et al. Risk factors for a first-incident radiographic vertebral fracture in women > or = 65 years of age: the study of osteoporotic fractures. J Bone Miner Res. 2005;20(1):131–40.PubMedCrossRef
34.
Rejnmark L, Vestergaard P, Mosekilde L. Reduced fracture risk in users of thiazide diuretics. Calcif Tissue Int. 2005;76(3):167–75.PubMedCrossRef
35.
Rejnmark L, Vestergaard P, Mosekilde L. Fracture risk in patients treated with loop diuretics. J Intern Med. 2006;259(1):117–24.PubMedCrossRef
36.
Carbone LD, Johnson KC, Bush AJ, Robbins J, Larson JC, Thomas A, LaCroix AZ. Loop diuretic use and fracture in postmenopausal women: findings from the Women's Health Initiative. Arch Intern Med. 2009;169(2):132–40.PubMedCrossRef
37.
38.
Wu TY, Majeed A, Kuo KN. An overview of the healthcare system in Taiwan. London J Prim Care (Abingdon). 2010;3(2):115–9.CrossRef
39.
Chou YC, Liao CC, Su LT, Yang PY, Sung FC. Stroke rehabilitation is associated with a reduction in dementia risk: a population-based retrospective cohort study. J Rehabil Med. 2012;44(4):319–24.PubMedCrossRef
40.
Chen YJ, Chang YT, Wang CB, Wu CY. The risk of cancer in patients with rheumatoid arthritis: a nationwide cohort study in Taiwan. Arthritis Rheum. 2011;63(2):352–8.PubMedCrossRef
41.
Tsan YT, Lee CH, Wang JD, Chen PC. Statins and the risk of hepatocellular carcinoma in patients with hepatitis B virus infection. J Clin Oncol. 2012;30(6):623–30.PubMedCrossRef
42.
Lin SM, Yang SH, Liang CC, Huang HK. Proton pump inhibitor use and the risk of osteoporosis and fracture in stroke patients: a population-based cohort study. Osteoporos Int. 2018;29(1):153–62.
43.
Lin SM, Yang SH, Cheng HY, Liang CC, Huang HK. Thiazide diuretics and the risk of hip fracture after stroke: a population-based propensity-matched cohort study using Taiwan's National Health Insurance Research Database. BMJ Open. 2017;7(9):e016992.PubMedPubMedCentralCrossRef
44.
Wang WJ, Chao CT, Huang YC, Wang CY, Chang CH, Huang TM, Lai CF, Huang HY, Shiao CC, Chu TS, et al. The impact of acute kidney injury with temporary dialysis on the risk of fracture. J Bone Miner Res. 2014;29(3):676–84.PubMedCrossRef
45.
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.PubMedCrossRef
46.
Wu JC, Liu L, Wen-Cheng H, Chen YC, Ko CC, Wu CL, Chen TJ, Cheng H, Su TP. The incidence of adjacent segment disease requiring surgery after anterior cervical diskectomy and fusion: estimation using an 11-year comprehensive nationwide database in Taiwan. Neurosurgery. 2012;70(3):594–601.PubMedCrossRef
47.
Lin HC, Chao PZ, Lee HC. Sudden sensorineural hearing loss increases the risk of stroke: a 5-year follow-up study. Stroke. 2008;39(10):2744–8.PubMedCrossRef
48.
Liu CYHY, Chuang YL, Chen YJ, Weng WS, KY LJSL. Incorporating development stratification of Taiwan townships into sampling design of large scale health interview survey (in Chinese). J Health Manag. 2006;4(1):1–22.
49.
Leung AA, Wright A, Pazo V, Karson A, Bates DW. Risk of thiazide-induced hyponatremia in patients with hypertension. Am J Med. 2011;124(11):1064–72.PubMedCrossRef
50.
Barber J, McKeever TM, McDowell SE, Clayton JA, Ferner RE, Gordon RD, Stowasser M, O'Shaughnessy KM, Hall IP, Glover M. A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation? Br J Clin Pharmacol. 2015;79(4):566–77.PubMedCrossRef
51.
Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med. 2006;119(1):71 e71–78.PubMedCrossRef
52.
Gankam Kengne F, Andres C, Sattar L, Melot C, Decaux G. Mild hyponatremia and risk of fracture in the ambulatory elderly. QJM. 2008;101(7):583–8.PubMedCrossRef
53.
Hoorn EJ, Liamis G, Zietse R, Zillikens MC. Hyponatremia and bone: an emerging relationship. Nat Rev Endocrinol. 2011;8(1):33–9.PubMedCrossRef
54.
Seeman E, Delmas PD. Bone quality--the material and structural basis of bone strength and fragility. N Engl J Med. 2006;354(21):2250–61.PubMedCrossRef
55.
Kruse C, Eiken P, Vestergaard P. Hyponatremia and osteoporosis: insights from the Danish National Patient Registry. Osteoporos Int. 2015;26(3):1005–16.PubMedCrossRef
56.
Seref-Ferlengez Z, Kennedy OD, Schaffler MB. Bone microdamage, remodeling and bone fragility: how much damage is too much damage? Bonekey Rep. 2015;4:644.PubMedPubMedCentralCrossRef
57.
Bolland MJ, Ames RW, Horne AM, Orr-Walker BJ, Gamble GD, Reid IR. The effect of treatment with a thiazide diuretic for 4 years on bone density in normal postmenopausal women. Osteoporos Int. 2007;18(4):479–86.PubMedCrossRef
58.
Kruse C, Eiken P, Vestergaard P. Continuous and long-term treatment is more important than dosage for the protective effect of thiazide use on bone metabolism and fracture risk. J Intern Med. 2016;279(1):110–22.PubMedCrossRef
59.
Rejnmark L, Vestergaard P, Pedersen AR, Heickendorff L, Andreasen F, Mosekilde L. 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 Investig. 2003;33(1):41–50.CrossRef
60.
Xiao F, Qu X, Zhai Z, Jiang C, Li H, Liu X, Ouyang Z, Gu D. Association between loop diuretic use and fracture risk. Osteoporos Int. 2015;26(2):775–84.PubMedCrossRef
61.
Poon IO, Braun U. High prevalence of orthostatic hypotension and its correlation with potentially causative medications among elderly veterans. J Clin Pharm Ther. 2005;30(2):173–8.PubMedCrossRef
62.
Harnod T, Wang YC, Kao CH. Association of Migraine and Sleep-Related Breathing Disorder: a population-based cohort study. Medicine (Baltimore). 2015;94(36):e1506.CrossRef
Metadata
Title
Association between diuretic use and the risk of vertebral fracture after stroke: a population-based retrospective cohort study
Authors
Shu-Man Lin
Shih-Hsien Yang
Chih-Yung Wang
Huei-Kai Huang
Publication date
01-12-2019
Publisher
BioMed Central
Keywords
Stroke
Diuretics
Published in
BMC Musculoskeletal Disorders / Issue 1/2019
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-019-2471-x

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