Top

Published in:

01-05-2014 | Original Article

Antidepressant use and 10-year incident fracture risk: the population-based Canadian Multicentre Osteoporosis Study (CaMoS)

Authors: C. Moura, S. Bernatsky, M. Abrahamowicz, A. Papaioannou, L. Bessette, J. Adachi, D. Goltzman, J. Prior, N. Kreiger, T. Towheed, W. D. Leslie, S. Kaiser, G. Ioannidis, L. Pickard, L.-A. Fraser, E. Rahme

Published in: Osteoporosis International | Issue 5/2014

Abstract

Summary

We used data from a large, prospective Canadian cohort to assess the association between selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) and fracture. We found an increased risk of fractures in individuals who used SSRI or SNRI, even after controlling for multiple risk factors.

Introduction

Previous studies have suggested an association between SSRIs and increasing risk of fragility fractures. However, the majority of these studies were not long-term analyses or were performed using administrative data and, thus, could not fully control for potential confounders. We sought to determine whether the use of SSRIs and SNRIs is associated with increased risk of fragility fracture, in adults aged 50 + .

Methods

We used data from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective randomly selected population-based community cohort; our analyses focused on subjects aged 50+. Time to event methodology was used to assess the association between SSRI/SNRI use, modeled time-dependently, and fragility fracture.

Results

Among 6,645 subjects, 192 (2.9 %) were using SSRIs or/and SNRIs at baseline. During the 10-year study period, 978 (14.7 %) participants experienced at least one fragility fracture. In our main analysis, SSRI/SNRI use was associated with increased risk of fragility fracture (hazard ratio (HR), 1.88; 95 % confidence intervals (CI), 1.48–2.39). After controlling for multiple risk factors, including Charlson score, previous falls, and bone mineral density hip and lumbar bone density, the adjusted HR for current SSRI/SNRI use remained elevated (HR, 1.68; 95 % CI, 1.32–2.14).

Conclusions

Our results lend additional support to an association between SSRI/SNRI use and fragility fractures. Given the high prevalence of antidepressants use, and the impact of fractures on health, our findings may have a significant clinical impact.

Adachi JD, Ioannidis G, Pickard L, Berger C, Prior JC, Joseph L, Hanley DA, Olszynski WP, Murray TM, Anastassiades T, Hopman W, Brown JP, Kirkland S, Joyce C, Papaioannou A, Poliquin S, Tenenhouse A, Papadimitropoulos EA (2003) The association between osteoporotic fractures and health-related quality of life as measured by the Health Utilities Index in the Canadian Multicentre Osteoporosis Study (CaMos). Osteoporos Int 14(11):895–904PubMedCrossRef

Papaioannou A, Morin S, Cheung AM, Atkinson S, Brown JP, Feldman S, Hanley DA, Hodsman A, Jamal SA, Kaiser SM, Kvern B, Siminoski K, Leslie WD (2010) 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. Cmaj 182(17):1864–1873PubMedCentralPubMedCrossRef

Berger C, Goltzman D, Langsetmo L, Joseph L, Jackson S, Kreiger N, Tenenhouse A, Davison KS, Josse RG, Prior JC, Hanley DA (2010) Peak bone mass from longitudinal data: implications for the prevalence, pathophysiology, and diagnosis of osteoporosis. J Bone Miner Res 25(9):1948–1957PubMedCrossRef

Richards JB, Papaioannou A, Adachi JD, Joseph L, Whitson HE, Prior JC, Goltzman D (2007) Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med 167(2):188–194PubMedCrossRef

Vestergaard P, Prieto-Alhambra D, Javaid MK, Cooper C (2013) Fractures in users of antidepressants and anxiolytics and sedatives: effects of age and dose. Osteoporos Int 24(2):671–680PubMedCentralPubMedCrossRef

Gribbin J, Hubbard R, Gladman J, Smith C, Lewis S (2011) Serotonin-norepinephrine reuptake inhibitor antidepressants and the risk of falls in older people: case–control and case-series analysis of a large UK primary care database. Drugs Aging 28(11):895–902PubMedCrossRef

Rabenda V, Nicolet D, Beaudart C, Bruyere O, Reginster JY (2013) Relationship between use of antidepressants and risk of fractures: a meta-analysis. Osteoporos Int 24(1):121–137PubMedCrossRef

Walker AM (1996) Confounding by indication. Epidemiology 7(4):335–336PubMed

Hansen DG, Rosholm JU, Gichangi A, Vach W (2007) Increased use of antidepressants at the end of life: population-based study among people aged 65 years and above. Age Ageing 36(4):449–454PubMedCrossRef

10.

Kreiger N, Tenenhouse A, Joseph L, Mackenzie T, Poliquin S, Brown JP, Prior JC, Rittmaster RS (1999) The Canadian Multicentre Osteoporosis Study (CaMos): background, rationale, methods. Can J Aging 18(3):376–387

11.

Vestergaard P, Rejnmark L, Mosekilde L (2006) Anxiolytics, sedatives, antidepressants, neuroleptics and the risk of fracture. Osteoporos Int 17(6):807–816PubMedCrossRef

12.

Fraser LA, Leslie WD, Targownik LE, Papaioannou A, Adachi JD (2013) The effect of proton pump inhibitors on fracture risk: report from the Canadian Multicenter Osteoporosis Study. Osteoporos Int 24(4):1161–1168PubMedCrossRef

13.

World Health Organization (2013) Guidelines for ATC classification and DDD assignment 2013, vol 16th. WHO Collaborating Centre for Drug Statistics Methodology, Oslo

14.

Genant HK, Grampp S, Gluer CC, Faulkner KG, Jergas M, Engelke K, Hagiwara S, Van Kuijk C (1994) Universal standardization for dual X-ray absorptiometry: patient and phantom cross-calibration results. J Bone Miner Res 9(10):1503–1514PubMedCrossRef

15.

Berwick DM, Murphy JM, Goldman PA, Ware JE Jr, Barsky AJ, Weinstein MC (1991) Performance of a five-item mental health screening test. Med Care 29(2):169–176PubMedCrossRef

16.

Rogers WH, Adler DA, Bungay KM, Wilson IB (2005) Depression screening instruments made good severity measures in a cross-sectional analysis. J Clin Epidemiol 58(4):370–377PubMedCrossRef

17.

Ware JEJ, Snow K, Kowinski M, Gandek B (1993) SF-36 Health Survey: manual and Interpretation Guide. 1st edn. The Health Institute, Boston

18.

Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8(9):1137–1148PubMedCrossRef

19.

Lenchik L, Rogers LF, Delmas PD, Genant HK (2004) Diagnosis of osteoporotic vertebral fractures: importance of recognition and description by radiologists. AJR Am J Roentgenol 183(4):949–958PubMedCrossRef

20.

Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40(5):373–383PubMedCrossRef

21.

Abrahamowicz M, Beauchamp ME, Sylvestre MP (2012) Comparison of alternative models for linking drug exposure with adverse effects. Stat Med 31(11–12):1014–1030PubMedCrossRef

22.

Abrahamowicz M, Tamblyn R (2005) Drug utilization patterns. In: Armitage P, Colton T (eds) Encyclopedia of biostatistics, vol 4, 2nd edn. Wiley, Chichester, pp 1533–1553

23.

Schwarz G (1978) Estimating the dimension of a model. The Annals of Statistics 6(2):461–464CrossRef

24.

Volinsky CT, Raftery AE (2000) Bayesian information criterion for censored survival models. Biometrics 56(1):256–262PubMedCrossRef

25.

Abrahamowicz M, MacKenzie TA (2007) Joint estimation of time-dependent and non-linear effects of continuous covariates on survival. Stat Med 26(2):392–408PubMedCrossRef

26.

Rubin DB, Schenker N (1991) Multiple imputation in health-care databases: an overview and some applications. Stat Med 10(4):585–598PubMedCrossRef

27.

Eom CS, Lee HK, Ye S, Park SM, Cho KH (2012) Use of selective serotonin reuptake inhibitors and risk of fracture: a systematic review and meta-analysis. J Bone Miner Res 27(5):1186–1195PubMedCrossRef

28.

Darowski A, Chambers SA, Chambers DJ (2009) Antidepressants and falls in the elderly. Drugs Aging 26(5):381–394PubMedCrossRef

29.

Thapa PB, Gideon P, Cost TW, Milam AB, Ray WA (1998) Antidepressants and the risk of falls among nursing home residents. N Engl J Med 339(13):875–882PubMedCrossRef

30.

Battaglino R, Fu J, Spate U, Ersoy U, Joe M, Sedaghat L, Stashenko P (2004) Serotonin regulates osteoclast differentiation through its transporter. J Bone Miner Res 19(9):1420–1431PubMedCrossRef

31.

Bliziotes M, Eshleman A, Burt-Pichat B, Zhang XW, Hashimoto J, Wiren K, Chenu C (2006) Serotonin transporter and receptor expression in osteocytic MLO-Y4 cells. Bone 39(6):1313–1321PubMedCentralPubMedCrossRef

32.

Diem SJ, Blackwell TL, Stone KL, Yaffe K, Haney EM, Bliziotes MM, Ensrud KE (2007) Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med 167(12):1240–1245PubMedCrossRef

33.

Haney EM, Chan BK, Diem SJ, Ensrud KE, Cauley JA, Barrett-Connor E, Orwoll E, Bliziotes MM (2007) Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med 167(12):1246–1251PubMedCrossRef

34.

Coupland C, Dhiman P, Morriss R, Arthur A, Barton G, Hippisley-Cox J (2011) Antidepressant use and risk of adverse outcomes in older people: population based cohort study. Bmj 343:d4551PubMedCentralPubMedCrossRef

35.

Gagne JJ, Patrick AR, Mogun H, Solomon DH (2011) Antidepressants and fracture risk in older adults: a comparative safety analysis. Clin Pharmacol Ther 89(6):880–887PubMedCrossRef

36.

Verdel BM, Souverein PC, Egberts TC, van Staa TP, Leufkens HG, de Vries F (2010) Use of antidepressant drugs and risk of osteoporotic and non-osteoporotic fractures. Bone 47(3):604–609PubMedCrossRef

37.

Bliziotes M (2010) Update in serotonin and bone. J Clin Endocrinol Metab 95(9):4124–4132PubMedCentralPubMedCrossRef

38.

Modder UI, Achenbach SJ, Amin S, Riggs BL, Melton LJ 3rd, Khosla S (2010) Relation of serum serotonin levels to bone density and structural parameters in women. J Bone Miner Res 25(2):415–422PubMedCentralPubMedCrossRef

39.

Kuchuk NO, Pluijm SM, van Schoor NM, Looman CW, Smit JH, Lips P (2009) Relationships of serum 25-hydroxyvitamin D to bone mineral density and serum parathyroid hormone and markers of bone turnover in older persons. J Clin Endocrinol Metab 94(4):1244–1250PubMedCrossRef

40.

Aydin H, Mutlu N, Akbas NB (2011) Treatment of a major depression episode suppresses markers of bone turnover in premenopausal women. J Psychiatr Res 45(10):1316–1320PubMedCrossRef

41.

Mussolino ME (2005) Depression and hip fracture risk: the NHANES I epidemiologic follow-up study. Public Health Rep 120(1):71–75PubMedCentralPubMed

42.

Whitson HE, Sanders L, Pieper CF, Gold DT, Papaioannou A, Richards JB, Adachi JD, Lyles KW (2008) Depressive symptomatology and fracture risk in community-dwelling older men and women. Aging Clin Exp Res 20(6):585–592PubMedCentralPubMedCrossRef

43.

Beusterien KM, Steinwald B, Ware JE Jr (1996) Usefulness of the SF-36 Health Survey in measuring health outcomes in the depressed elderly. J Geriatr Psychiatry Neurol 9(1):13–21PubMedCrossRef

44.

Wells KB, Hays RD, Burnam MA, Rogers W, Greenfield S, Ware JE Jr (1989) Detection of depressive disorder for patients receiving prepaid or fee-for-service care. Results from the Medical Outcomes Study. JAMA 262(23):3298–3302PubMedCrossRef

Title: Antidepressant use and 10-year incident fracture risk: the population-based Canadian Multicentre Osteoporosis Study (CaMoS)
Authors: C. Moura
S. Bernatsky
M. Abrahamowicz
A. Papaioannou
L. Bessette
J. Adachi
D. Goltzman
J. Prior
N. Kreiger
T. Towheed
W. D. Leslie
S. Kaiser
G. Ioannidis
L. Pickard
L.-A. Fraser
E. Rahme
Publication date: 01-05-2014
Publisher: Springer London
Published in: Osteoporosis International / Issue 5/2014
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-014-2649-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Antidepressant use and 10-year incident fracture risk: the population-based Canadian Multicentre Osteoporosis Study (CaMoS)

Abstract

Summary

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 5/2014

Refracture of osteoporotic vertebral body concurrent with cement fragmentation at the previously treated vertebral level after balloon kyphoplasty: a case report

Incidence and risk of osteonecrosis of the jaw among the Taiwan osteoporosis population

Theoretical consideration of the effect of drug holidays on BMD and tissue age

Vitamin D status of schoolchildren in Northern Algeria, seasonal variations and determinants of vitamin D deficiency

Comparison of interactive voice response, patient mailing, and mailed registry to encourage screening for osteoporosis: a randomized controlled trial

Erratum to: Impact of vitamin D fortified milk supplementation on vitamin D status of healthy school children aged 10–14 years