Skip to main content
Top
Published in: Osteoporosis International 6/2018

01-06-2018 | Original Article

Depression and risk of fracture and bone loss: an updated meta-analysis of prospective studies

Authors: Q. Wu, B. Liu, S. Tonmoy

Published in: Osteoporosis International | Issue 6/2018

Login to get access

Abstract

Summary

This meta-analysis pooled results from 23 qualifying individual cohort studies and found that depression was significantly associated with an increased risk of fractures and bone loss.

Introduction

The association between depression and risk of fracture remains controversial. We conducted a comprehensive meta-analysis to examine the effect of depression on the risk of osteoporotic fractures and bone loss.

Methods

We searched databases and reviewed citations in relevant articles for eligible cohort studies. Two investigators independently conducted study selection, appraisal, and data abstraction through the use of a standardized protocol. Random effect models were used for meta-analysis. Cochrane Q and I2 statistics were used to assess heterogeneity. Funnel plots and rank correlation tests were used to evaluate publication bias.

Results

Twenty-three studies were included for meta-analysis. In studies that reported hazard ratio (HR) as the outcome (nine studies [n = 309,862]), depression was associated with 26% increase in fracture risk (HR = 1.26, 95% CI, 1.10–1.43, p < 0.001). Studies that reported risk ratio (RR) as the outcome (seven studies [n = 64,975]) suggested that depression was associated with 39% increase in fracture risk (RR = 1.39, 95% CI, 1.19–1.62, p < 0.001). Among studies that reported hip bone mineral density (BMD) as an outcome (eight studies [n = 15,442]), depression was associated with a reduced mean annual bone loss rate of 0.35% (0.18–0.53%, p < 0.001). The increased risk of fracture and bone loss associated with depression was consistent in all meta-analysis having modified inclusion criteria and in different subgroup analyses as well. Significant heterogeneity was observed in the meta-analysis; however, no significant publication bias was detected.

Conclusion

Depression is associated with a significant increased risk in fracture and bone loss. Effective prevention may decrease such risk.
Appendix
Available only for authorised users
Literature
1.
go back to reference Johnell O, Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17:1726–1733CrossRefPubMed Johnell O, Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17:1726–1733CrossRefPubMed
2.
go back to reference Melton LJ, Atkinson EJ, O'Connor MK, O'Fallon WM, Riggs BL (1998) Bone density and fracture risk in men. J Bone Miner Res 13:1915–1923CrossRefPubMed Melton LJ, Atkinson EJ, O'Connor MK, O'Fallon WM, Riggs BL (1998) Bone density and fracture risk in men. J Bone Miner Res 13:1915–1923CrossRefPubMed
3.
go back to reference Melton LJ, Chrischilles EA, Cooper C, Lane AW, Riggs BL (1992) Perspective. How many women have osteoporosis? J Bone Miner Res 7:1005–1010CrossRefPubMed Melton LJ, Chrischilles EA, Cooper C, Lane AW, Riggs BL (1992) Perspective. How many women have osteoporosis? J Bone Miner Res 7:1005–1010CrossRefPubMed
4.
go back to reference Gullberg B, Johnell O, Kanis JA (1997) World-wide projections for hip fracture. Osteoporos Int 7:407–413CrossRefPubMed Gullberg B, Johnell O, Kanis JA (1997) World-wide projections for hip fracture. Osteoporos Int 7:407–413CrossRefPubMed
5.
go back to reference Hernlund E, Svedbom A, Ivergård M, Compston J, Cooper C, Stenmark J, McCloskey EV, Jönsson B, Kanis JA (2013) Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 8:136CrossRefPubMedPubMedCentral Hernlund E, Svedbom A, Ivergård M, Compston J, Cooper C, Stenmark J, McCloskey EV, Jönsson B, Kanis JA (2013) Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 8:136CrossRefPubMedPubMedCentral
6.
go back to reference Shim RS, Baltrus P, Ye J, Rust G (2011) Prevalence, treatment, and control of depressive symptoms in the United States: results from the National Health and Nutrition Examination Survey (NHANES), 2005-2008. J Am Board Fam Med 24:33–38CrossRefPubMedPubMedCentral Shim RS, Baltrus P, Ye J, Rust G (2011) Prevalence, treatment, and control of depressive symptoms in the United States: results from the National Health and Nutrition Examination Survey (NHANES), 2005-2008. J Am Board Fam Med 24:33–38CrossRefPubMedPubMedCentral
7.
go back to reference Kessler RC, Ustün TB (2004) The World Mental Health (WMH) survey initiative version of the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI). Int J Methods Psychiatr Res 13:93–121CrossRefPubMed Kessler RC, Ustün TB (2004) The World Mental Health (WMH) survey initiative version of the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI). Int J Methods Psychiatr Res 13:93–121CrossRefPubMed
8.
go back to reference Schweiger JU, Schweiger U, Hüppe M, Kahl KG, Greggersen W, Fassbinder E (2016) Bone density and depressive disorder: a meta-analysis. Brain Behav 6:e00489CrossRefPubMedPubMedCentral Schweiger JU, Schweiger U, Hüppe M, Kahl KG, Greggersen W, Fassbinder E (2016) Bone density and depressive disorder: a meta-analysis. Brain Behav 6:e00489CrossRefPubMedPubMedCentral
9.
go back to reference Stubbs B, Brefka S, Dallmeier D, Stubbs J, Vancampfort D, Denkinger MD (2016) Depression and reduced bone mineral density at the hip and lumbar spine: a comparative meta-analysis of studies in adults 60 years and older. Psychosom Med 78:492–500CrossRefPubMed Stubbs B, Brefka S, Dallmeier D, Stubbs J, Vancampfort D, Denkinger MD (2016) Depression and reduced bone mineral density at the hip and lumbar spine: a comparative meta-analysis of studies in adults 60 years and older. Psychosom Med 78:492–500CrossRefPubMed
10.
go back to reference Wu Q, Magnus JH, Liu J, Bencaz AF, Hentz JG (2009) Depression and low bone mineral density: a meta-analysis of epidemiologic studies. Osteoporos Int 20:1309–1320CrossRefPubMed Wu Q, Magnus JH, Liu J, Bencaz AF, Hentz JG (2009) Depression and low bone mineral density: a meta-analysis of epidemiologic studies. Osteoporos Int 20:1309–1320CrossRefPubMed
11.
go back to reference Yirmiya R, Bab I (2009) Major depression is a risk factor for low bone mineral density: a meta-analysis. Biol Psychiatry 66:423–432CrossRefPubMed Yirmiya R, Bab I (2009) Major depression is a risk factor for low bone mineral density: a meta-analysis. Biol Psychiatry 66:423–432CrossRefPubMed
12.
go back to reference Wu Q, Liu J, Gallegos-Orozco JF, Hentz JG (2010) Depression, fracture risk, and bone loss: a meta-analysis of cohort studies. Osteoporos Int 21:1627–1635CrossRefPubMed Wu Q, Liu J, Gallegos-Orozco JF, Hentz JG (2010) Depression, fracture risk, and bone loss: a meta-analysis of cohort studies. Osteoporos Int 21:1627–1635CrossRefPubMed
13.
go back to reference Diem SJ, Harrison SL, Haney E, Cauley JA, Stone KL, Orwoll E, Ensrud KE, Osteoporotic Fractures in Men Research, G (2013) Depressive symptoms and rates of bone loss at the hip in older men. Osteoporos Int 24:111–119CrossRefPubMed Diem SJ, Harrison SL, Haney E, Cauley JA, Stone KL, Orwoll E, Ensrud KE, Osteoporotic Fractures in Men Research, G (2013) Depressive symptoms and rates of bone loss at the hip in older men. Osteoporos Int 24:111–119CrossRefPubMed
14.
go back to reference Diem SJ, Ruppert K, Cauley JA, Lian Y, Bromberger JT, Finkelstein JS, Greendale GA, Solomon DH (2013) Rates of bone loss among women initiating antidepressant medication use in midlife. J Clin Endocrinol Metab 98:4355–4363CrossRefPubMedPubMedCentral Diem SJ, Ruppert K, Cauley JA, Lian Y, Bromberger JT, Finkelstein JS, Greendale GA, Solomon DH (2013) Rates of bone loss among women initiating antidepressant medication use in midlife. J Clin Endocrinol Metab 98:4355–4363CrossRefPubMedPubMedCentral
15.
go back to reference Cheng B-H, Chen P-C, Yang Y-H, Lee C-P, Huang K-E, Chen VC (2016) Effects of depression and antidepressant medications on hip fracture: a population-based cohort study in Taiwan. Medicine (Baltimore) 95:e4655CrossRef Cheng B-H, Chen P-C, Yang Y-H, Lee C-P, Huang K-E, Chen VC (2016) Effects of depression and antidepressant medications on hip fracture: a population-based cohort study in Taiwan. Medicine (Baltimore) 95:e4655CrossRef
16.
go back to reference Williams LJ, Pasco JA, Jackson H, Kiropoulos L, Stuart AL, Jacka FN, Berk M (2016) Depression as a risk factor for fracture in women: a 10 year longitudinal study. J Affect Disord 192:34–40CrossRefPubMed Williams LJ, Pasco JA, Jackson H, Kiropoulos L, Stuart AL, Jacka FN, Berk M (2016) Depression as a risk factor for fracture in women: a 10 year longitudinal study. J Affect Disord 192:34–40CrossRefPubMed
18.
go back to reference Gale CR, Dennison EM, Edwards M, Sayer AA, Cooper C (2012) Symptoms of anxiety or depression and risk of fracture in older people: the Hertfordshire cohort study. Arch Osteoporos 7:59–65CrossRefPubMedPubMedCentral Gale CR, Dennison EM, Edwards M, Sayer AA, Cooper C (2012) Symptoms of anxiety or depression and risk of fracture in older people: the Hertfordshire cohort study. Arch Osteoporos 7:59–65CrossRefPubMedPubMedCentral
19.
go back to reference Cizza G, Mistry S, Nguyen VT, Eskandari F, Martinez P, Torvik S, Reynolds JC, Gold PW, Sinaii N, Sinai N, Csako G, Group, P. S (2012) Do premenopausal women with major depression have low bone mineral density? A 36-month prospective study. PLoS One 7:e40894CrossRefPubMedPubMedCentral Cizza G, Mistry S, Nguyen VT, Eskandari F, Martinez P, Torvik S, Reynolds JC, Gold PW, Sinaii N, Sinai N, Csako G, Group, P. S (2012) Do premenopausal women with major depression have low bone mineral density? A 36-month prospective study. PLoS One 7:e40894CrossRefPubMedPubMedCentral
20.
go back to reference Jørgensen TSH, Hansen AH, Sahlberg M, Gislason GH, Torp-Pedersen C, Andersson C, Holm E (2015) Nationwide time trends and risk factors for in-hospital falls-related major injuries. Int J Clin Pract 69:703–709CrossRefPubMed Jørgensen TSH, Hansen AH, Sahlberg M, Gislason GH, Torp-Pedersen C, Andersson C, Holm E (2015) Nationwide time trends and risk factors for in-hospital falls-related major injuries. Int J Clin Pract 69:703–709CrossRefPubMed
21.
go back to reference Rauma PH, Honkanen RJ, Williams LJ, Tuppurainen MT, Kröger HP, Koivumaa-Honkanen H (2016) Effects of antidepressants on postmenopausal bone loss—a 5-year longitudinal study from the OSTPRE cohort. Bone 89:25–31CrossRefPubMed Rauma PH, Honkanen RJ, Williams LJ, Tuppurainen MT, Kröger HP, Koivumaa-Honkanen H (2016) Effects of antidepressants on postmenopausal bone loss—a 5-year longitudinal study from the OSTPRE cohort. Bone 89:25–31CrossRefPubMed
22.
go back to reference Bolton JM, Morin SN, Majumdar SR, Sareen J, Lix LM, Johansson H, Odén A, McCloskey EV, Kanis JA, Leslie WD (2017) Association of mental disorders and related medication use with risk for major osteoporotic fractures. JAMA Psychiatry 74:641–648CrossRefPubMedPubMedCentral Bolton JM, Morin SN, Majumdar SR, Sareen J, Lix LM, Johansson H, Odén A, McCloskey EV, Kanis JA, Leslie WD (2017) Association of mental disorders and related medication use with risk for major osteoporotic fractures. JAMA Psychiatry 74:641–648CrossRefPubMedPubMedCentral
23.
go back to reference Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–2012CrossRefPubMed Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–2012CrossRefPubMed
24.
go back to reference Moher D, Liberati A, Tetzlaff J, Altman DG, Group, P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(264–269):W64 Moher D, Liberati A, Tetzlaff J, Altman DG, Group, P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(264–269):W64
25.
go back to reference Davidson GC, Neale JM (2001) Abnormal psychology, 6th edn. John Wiley, New York Davidson GC, Neale JM (2001) Abnormal psychology, 6th edn. John Wiley, New York
26.
go back to reference Whooley MA, Kip KE, Cauley JA, Ensrud KE, Nevitt MC, Browner WS (1999) Depression, falls, and risk of fracture in older women. Study of Osteoporotic Fractures Research Group. Arch Intern Med 159:484–490CrossRefPubMed Whooley MA, Kip KE, Cauley JA, Ensrud KE, Nevitt MC, Browner WS (1999) Depression, falls, and risk of fracture in older women. Study of Osteoporotic Fractures Research Group. Arch Intern Med 159:484–490CrossRefPubMed
28.
go back to reference Forsén L, Meyer HE, Søgaard AJ, Naess S, Schei B, Edna TH (1999) Mental distress and risk of hip fracture. Do broken hearts lead to broken bones? J Epidemiol Community Health 53:343–347CrossRefPubMedPubMedCentral Forsén L, Meyer HE, Søgaard AJ, Naess S, Schei B, Edna TH (1999) Mental distress and risk of hip fracture. Do broken hearts lead to broken bones? J Epidemiol Community Health 53:343–347CrossRefPubMedPubMedCentral
29.
go back to reference Søgaard AJ, Joakimsen RM, Tverdal A, Fønnebø V, Magnus JH, Berntsen GKR (2005) Long-term mental distress, bone mineral density and non-vertebral fractures. The Tromsø study. Osteoporos Int 16:887–897CrossRefPubMed Søgaard AJ, Joakimsen RM, Tverdal A, Fønnebø V, Magnus JH, Berntsen GKR (2005) Long-term mental distress, bone mineral density and non-vertebral fractures. The Tromsø study. Osteoporos Int 16:887–897CrossRefPubMed
30.
go back to reference Piirtola M, Vahlberg T, Isoaho R, Aarnio P, Kivelä S-L (2008) Predictors of fractures among the aged: a population-based study with 12-year follow-up in a Finnish municipality. Aging Clin Exp Res 20:242–252CrossRefPubMed Piirtola M, Vahlberg T, Isoaho R, Aarnio P, Kivelä S-L (2008) Predictors of fractures among the aged: a population-based study with 12-year follow-up in a Finnish municipality. Aging Clin Exp Res 20:242–252CrossRefPubMed
31.
go back to reference Tolea MI, Black SA, Carter-Pokras OD, Kling MA (2007) Depressive symptoms as a risk factor for osteoporosis and fractures in older Mexican American women. Osteoporos Int 18:315–322CrossRefPubMed Tolea MI, Black SA, Carter-Pokras OD, Kling MA (2007) Depressive symptoms as a risk factor for osteoporosis and fractures in older Mexican American women. Osteoporos Int 18:315–322CrossRefPubMed
32.
go back to reference 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 20:585–592CrossRefPubMedPubMedCentral 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 20:585–592CrossRefPubMedPubMedCentral
33.
go back to reference Ojo F, Al Snih S, Ray LA, Raji MA, Markides KS (2007) History of fractures as predictor of subsequent hip and nonhip fractures among older Mexican Americans. J Natl Med Assoc 99:412–418PubMedPubMedCentral Ojo F, Al Snih S, Ray LA, Raji MA, Markides KS (2007) History of fractures as predictor of subsequent hip and nonhip fractures among older Mexican Americans. J Natl Med Assoc 99:412–418PubMedPubMedCentral
34.
go back to reference Lewis CE, Ewing SK, Taylor BC, Shikany JM, Fink HA, Ensrud KE, Barrett-Connor E, Cummings SR, Orwoll E (2007) Predictors of non-spine fracture in elderly men: the MrOS study. J Bone Miner Res 22:211–219CrossRefPubMed Lewis CE, Ewing SK, Taylor BC, Shikany JM, Fink HA, Ensrud KE, Barrett-Connor E, Cummings SR, Orwoll E (2007) Predictors of non-spine fracture in elderly men: the MrOS study. J Bone Miner Res 22:211–219CrossRefPubMed
35.
go back to reference Spangler L, Scholes D, Brunner RL, Robbins J, Reed SD, Newton KM, Melville JL, Lacroix AZ (2008) Depressive symptoms, bone loss, and fractures in postmenopausal women. J Gen Intern Med 23:567–574CrossRefPubMedPubMedCentral Spangler L, Scholes D, Brunner RL, Robbins J, Reed SD, Newton KM, Melville JL, Lacroix AZ (2008) Depressive symptoms, bone loss, and fractures in postmenopausal women. J Gen Intern Med 23:567–574CrossRefPubMedPubMedCentral
36.
go back to reference Whooley MA, Cauley JA, Zmuda JM, Haney EM, Glynn NW (2004) Depressive symptoms and bone mineral density in older men. J Geriatr Psychiatry Neurol 17:88–92CrossRefPubMed Whooley MA, Cauley JA, Zmuda JM, Haney EM, Glynn NW (2004) Depressive symptoms and bone mineral density in older men. J Geriatr Psychiatry Neurol 17:88–92CrossRefPubMed
37.
go back to reference Milliken LA, Wilhelmy J, Martin CJ, Finkenthal N, Cussler E, Metcalfe L, Guido TA, Going SB, Lohman TG (2006) Depressive symptoms and changes in body weight exert independent and site-specific effects on bone in postmenopausal women exercising for 1 year. J Gerontol A Biol Sci Med Sci 61:488–494CrossRefPubMed Milliken LA, Wilhelmy J, Martin CJ, Finkenthal N, Cussler E, Metcalfe L, Guido TA, Going SB, Lohman TG (2006) Depressive symptoms and changes in body weight exert independent and site-specific effects on bone in postmenopausal women exercising for 1 year. J Gerontol A Biol Sci Med Sci 61:488–494CrossRefPubMed
38.
go back to reference 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 167:1240–1245CrossRefPubMed 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 167:1240–1245CrossRefPubMed
41.
go back to reference Ganesan K, Teklehaimanot S, Tran T-H, Asuncion M, Norris K (2005) Relationship of C-reactive protein and bone mineral density in community-dwelling elderly females. J Natl Med Assoc 97:329–333PubMedPubMedCentral Ganesan K, Teklehaimanot S, Tran T-H, Asuncion M, Norris K (2005) Relationship of C-reactive protein and bone mineral density in community-dwelling elderly females. J Natl Med Assoc 97:329–333PubMedPubMedCentral
43.
go back to reference Gkiatas I, Lykissas M, Kostas-Agnantis I, Korompilias A, Batistatou A, Beris A (2015) Factors affecting bone growth. Am J Orthop Belle Mead NJ 44:61–67PubMed Gkiatas I, Lykissas M, Kostas-Agnantis I, Korompilias A, Batistatou A, Beris A (2015) Factors affecting bone growth. Am J Orthop Belle Mead NJ 44:61–67PubMed
45.
go back to reference Anstey KJ, Burns R, von Sanden C, Luszcz MA (2008) Psychological well-being is an independent predictor of falling in an 8-year follow-up of older adults. J Gerontol B Psychol Sci Soc Sci 63:P249–P257CrossRefPubMed Anstey KJ, Burns R, von Sanden C, Luszcz MA (2008) Psychological well-being is an independent predictor of falling in an 8-year follow-up of older adults. J Gerontol B Psychol Sci Soc Sci 63:P249–P257CrossRefPubMed
Metadata
Title
Depression and risk of fracture and bone loss: an updated meta-analysis of prospective studies
Authors
Q. Wu
B. Liu
S. Tonmoy
Publication date
01-06-2018
Publisher
Springer London
Published in
Osteoporosis International / Issue 6/2018
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-018-4420-1

Other articles of this Issue 6/2018

Osteoporosis International 6/2018 Go to the issue