Osteoporosis International

, Volume 21, Issue 10, pp 1627–1635 | Cite as

Depression, fracture risk, and bone loss: a meta-analysis of cohort studies

  • Q. Wu
  • J. Liu
  • J. F. Gallegos-Orozco
  • J. G. Hentz



Whether depression can increase the risk of bone fractures is uncertain. This meta-analysis, which pooled results from 14 qualifying individual cohort studies, found that depression was associated with a significantly increased risk of fractures and bone loss.


The effect of depression on the risk of bone fractures is controversial. We conducted a meta-analysis of prospective studies that examined the risk of osteoporotic fractures and bone loss associated with depression.


We searched databases and reviewed citations in relevant articles to identify cohort studies that met prestated inclusion criteria; 14 studies were identified. Information on study design, participant characteristics, exposure and outcome measures, control for potential confounders, and risk estimates was abstracted independently by two investigators using a standardized protocol. Data were pooled by use of a random-effects model.


In studies that reported fracture outcomes as hazard ratios (HRs) (six studies [n = 108,157]), depression was associated with a 17% increase in fracture risk (HR = 1.17; 95% confidence interval [CI], 1.00–1.36; P = 0.05); in studies that reported risk ratios as fracture outcomes (four studies [n = 33,428]), depression was associated with a 52% increase in risk (risk ratio, 1.52; 95% CI, 1.26–1.85; P < 0.001). In studies that reported bone mineral density as an outcome (five studies [n = 8,931]), depression was associated with a reduced annualized bone loss rate of 0.25% (0.05–0.45%; P = 0.02) at the hip and 0.29% (−0.07–0.64%; P = 0.11) at the spine. The HR for the three studies (n = 14,777) that did not adjust for antidepressant treatment was 1.30 (95% CI, 1.11–1.52; P = 0.01), and the HR for the three studies (n = 93,380) that did adjust for antidepressant treatment was 1.05 (95% CI, 0.86–1.29; P = 0.6).


Evidence supports an association between depression and increased risk of fracture and bone loss that may be mediated by antidepressants.


Depression Depressive disorder Fractures Bone Meta-analysis Review 



Bone mineral density


Cochrane Database of Systematic Reviews


Confidence interval


Database of Abstracts of Reviews of Effects


Hazard ratio


Odds ratio


Risk ratio


Conflicts of interest



  1. 1.
    U.S. Department of Health and Human Services, Public Health Service, Office of the Surgeon General. Bone health and osteoporosis: a report of the Surgeon General 2004 [Internet]. Rockville (MD): U.S. Department of Health and Human Services, Public Health Service, Office of the Surgeon General; 2004 Oct 14 [cited 2009 Aug 17]. Available from: http://www.surgeongeneral.gov/library/bonehealth/index.html.
  2. 2.
    Sambrook P, Cooper C (2006) Osteoporosis. Lancet 367(9527):2010–2018, Erratum in: Lancet. 2006 Jul 1;368(9529):28CrossRefPubMedGoogle Scholar
  3. 3.
    Melton LJ 3rd, Cooper C (2001) Magnitude and impact of osteoporosis and fractures. In: Marcus R, Feldman D, Kelsey J (eds) osteoporosis, vol 1, 2nd edn. Academic, San Diego, pp 557–67Google Scholar
  4. 4.
    Kessler RC, Birnbaum H, Bromet E, Hwang I, Sampson N, Shahly V (2009) Age differences in major depression: results from the National Comorbidity Survey Replication (NCS-R). Psychol Med 17:1–13 [Epub ahead of print]Google Scholar
  5. 5.
    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(8):1309–1320, Epub 2009 Apr 3CrossRefPubMedGoogle Scholar
  6. 6.
    Mezuk B, Eaton WW, Golden SH (2008) Depression and osteoporosis: epidemiology and potential mediating pathways. Osteoporos Int 19(1):1–12, Epub 2007 Sep 1CrossRefPubMedGoogle Scholar
  7. 7.
    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(5):484–490CrossRefPubMedGoogle Scholar
  8. 8.
    Mussolino ME (2005) Depression and hip fracture risk: the NHANES I epidemiologic follow-up study. Public Health Rep 120(1):71–75PubMedGoogle Scholar
  9. 9.
    Forsen L, Meyer HE, Sogaard 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(6):343–347CrossRefPubMedGoogle Scholar
  10. 10.
    Sogaard AJ, Joakimsen RM, Tverdal A, Fonnebo V, Magnus JH, Berntsen GK (2005) Long-term mental distress, bone mineral density and non-vertebral fractures: the Tromso Study. Osteoporos Int 16(8):887–897, Epub 2004 Dec 24CrossRefPubMedGoogle Scholar
  11. 11.
    Piirtola M, Vahlberg T, Isoaho R, Aarnio P, Kivela SL (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(3):242–252PubMedGoogle Scholar
  12. 12.
    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(3):315–322, Epub 2006 Oct 20CrossRefPubMedGoogle Scholar
  13. 13.
    Whitson HE, Sanders L, Pieper CF, Gold DT, Papaioannou A, Richards JB, CaMos Research Group et al (2008) Depressive symptomatology and fracture risk in community-dwelling older men and women. Aging Clin Exp Res 20(6):585–592PubMedGoogle Scholar
  14. 14.
    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(4):412–418PubMedGoogle Scholar
  15. 15.
    Cizza G, Ravn P, Chrousos GP, Gold PW (2001) Depression: a major, unrecognized risk factor for osteoporosis? Trends Endocrinol Metab 12(5):198–203CrossRefPubMedGoogle Scholar
  16. 16.
    Gold DT, Solimeo S (2006) Osteoporosis and depression: a historical perspective. Curr Osteoporos Rep 4(4):134–139CrossRefPubMedGoogle Scholar
  17. 17.
    Lewis CE, Ewing SK, Taylor BC, Shikany JM, Fink HA, Ensrud KE, Osteoporotic Fractures in Men (MrOS) Study Research Group et al (2007) Predictors of non-spine fracture in elderly men: the MrOS study. J Bone Miner Res 22(2):211–219CrossRefPubMedGoogle Scholar
  18. 18.
    Spangler L, Scholes D, Brunner RL, Robbins J, Reed SD, Newton KM et al (2008) Depressive symptoms, bone loss, and fractures in postmenopausal women. J Gen Intern Med 23(5):567–574, Epub 2008 Feb 20CrossRefPubMedGoogle Scholar
  19. 19.
    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(2):88–92CrossRefPubMedGoogle Scholar
  20. 20.
    Milliken LA, Wilhelmy J, Martin CJ, Finkenthal N, Cussler E, Metcalfe L et al (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(5):488–494PubMedGoogle Scholar
  21. 21.
    Diem SJ, Blackwell TL, Stone KL, Yaffe K, Haney EM, Bliziotes MM et al (2007) Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med 167(12):1240–1245CrossRefPubMedGoogle Scholar
  22. 22.
    Schweiger U, Weber B, Deuschle M, Heuser I (2000) Lumbar bone mineral density in patients with major depression: evidence of increased bone loss at follow-up. Am J Psychiatry 157(1):118–120PubMedGoogle Scholar
  23. 23.
    Walter SD, Cook RJ (1991) A comparison of several point estimators of the odds ratio in a single 2 × 2 contingency table. Biometrics 47(3):795–811CrossRefPubMedGoogle Scholar
  24. 24.
    Kahn HA, Sempos CT (1989) Statistical methods in epidemiology. Vol. 12, Monographs in epidemiology and biostatistics. Oxford University Press, New York, p. 292.Google Scholar
  25. 25.
    Gavaghan DJ, Moore RA, McQuay HJ (2000) An evaluation of homogeneity tests in meta-analyses in pain using simulations of individual patient data. Pain 85(3):415–424CrossRefPubMedGoogle Scholar
  26. 26.
    Furukawa TA, Guyatt GH, Griffith LE (2002) Can we individualize the ‘number needed to treat’? An empirical study of summary effect measures in meta-analyses. Int J Epidemiol 31(1):72–76CrossRefPubMedGoogle Scholar
  27. 27.
    Mezuk B, Eaton WW, Golden SH, Wand G, Lee HB (2008) Depression, antidepressants, and bone mineral density in a population-based cohort. J Gerontol A Biol Sci Med Sci 63(12):1410–1415PubMedGoogle Scholar
  28. 28.
    Malkin I, Bigman G, Matias R, Kalichman L, Seibel MJ, Kobyliansky E et al (2006) Age-related changes of bone strength phenotypes: observational follow-up study of hand bone mineral density. Osteoporos Int 1:59–68Google Scholar
  29. 29.
    Kaji H, Kosaka R, Yamauchi M, Kuno K, Chihara K, Sugimoto T (2005) Effects of age, grip strength and smoking on forearm volumetric bone mineral density and bone geometry by peripheral quantitative computed tomography: comparisons between female and male. Endocr J 52(6):659–666CrossRefPubMedGoogle Scholar
  30. 30.
    Kato Y, Ishikawa-Takata K, Yasaku K, Okawa Y, Kawakami O, Ohta T (2005) Changes in metacarpal bone mineral density with age and menopause using computed X-ray densitometry in Japanese women: cross-sectional and longitudinal study. Ann Hum Biol 32(6):760–772CrossRefPubMedGoogle Scholar
  31. 31.
    Zhang HC, Kushida K, Atsumi K, Kin K, Nagano A (2002) Effects of age and menopause on spinal bone mineral density in Japanese women: a ten-year prospective study. Calcif Tissue Int 70(3):153–157, Epub 2002 Jan 30CrossRefPubMedGoogle Scholar
  32. 32.
    Kanis JA, Johansson H, Oden A, McCloskey EV (2009) Assessment of fracture risk. Eur J Radiol 71(3):392–397, Epub 2009 Aug 28CrossRefGoogle Scholar
  33. 33.
    Cummings SR, Nevitt MC (1989) A hypothesis: the causes of hip fractures. J Gerontol 44(4):M107–M111PubMedGoogle Scholar
  34. 34.
    Kahl KG, Greggersen W, Rudolf S, Stoeckelhuber BM, Bergmann-Koester CU, Dibbelt L et al (2006) Bone mineral density, bone turnover, and osteoprotegerin in depressed women with and without borderline personality disorder. Psychosom Med 68(5):669CrossRefPubMedGoogle Scholar
  35. 35.
    Altindag O, Altindag A, Asoglu M, Gunes M, Soran N, Deveci Z (2007) Relation of cortisol levels and bone mineral density among premenopausal women with major depression. Int J Clin Pract 61(3):416–420CrossRefPubMedGoogle Scholar
  36. 36.
    Herran A, Amado JA, Garcia-Unzueta MT, Vazquez-Barquero JL, Perera L, Gonzalez-Macias J (2000) Increased bone remodeling in first-episode major depressive disorder. Psychosom Med 62(6):779–782PubMedGoogle Scholar
  37. 37.
    Anda RF, Williamson DF, Escobedo LG, Mast EE, Giovino GA, Remington PL (1990) Depression and the dynamics of smoking: a national perspective. JAMA 264(12):1541–1545CrossRefPubMedGoogle Scholar
  38. 38.
    Grant BF, Harford TC (1995) Comorbidity between DSM-IV alcohol use disorders and major depression: results of a national survey. Drug Alcohol Depend 39(3):197–206CrossRefPubMedGoogle Scholar
  39. 39.
    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(4):P249–P257PubMedGoogle Scholar
  40. 40.
    Takkouche B, Montes-Martinez A, Gill SS, Etminan M (2007) Psychotropic medications and the risk of fracture: a meta-analysis. Drug Saf 30(2):171–184CrossRefPubMedGoogle Scholar
  41. 41.
    Henkel V, Mergl R, Kohnen R, Maier W, Moller HJ, Hegerl U (2003) Identifying depression in primary care: a comparison of different methods in a prospective cohort study. BMJ 326(7382):200–201CrossRefPubMedGoogle Scholar
  42. 42.
    Andresen EM, Malmgren JA, Carter WB, Patrick DL (1994) Screening for depression in well older adults: evaluation of a short form of the CES-D (Center for Epidemiologic Studies Depression Scale). Am J Prev Med 10(2):77–84PubMedGoogle Scholar
  43. 43.
    Kinjo M, Setoguchi S, Schneeweiss S, Solomon DH (2005) Bone mineral density in subjects using central nervous system-active medications. Am J Med 118(12):1414CrossRefPubMedGoogle Scholar
  44. 44.
    Romas E (2005) Bone loss in inflammatory arthritis: mechanisms and therapeutic approaches with bisphosphonates. Best Pract Res Clin Rheumatol 19(6):1065–1079CrossRefPubMedGoogle Scholar
  45. 45.
    Harpavat M, Keljo DJ, Regueiro MD (2004) Metabolic bone disease in inflammatory bowel disease. J Clin Gastroenterol 38(3):218–224CrossRefPubMedGoogle Scholar
  46. 46.
    Jorde R, Sneve M, Figenschau Y, Svartberg J, Waterloo K (2008) Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. J Intern Med 264(6):599–609, Epub 2008 Sep 10CrossRefPubMedGoogle Scholar
  47. 47.
    Murphy PK, Wagner CL (2008) Vitamin D and mood disorders among women: an integrative review. J Midwifery Womens Health 53(5):440–446CrossRefPubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2010

Authors and Affiliations

  • Q. Wu
    • 1
  • J. Liu
    • 2
  • J. F. Gallegos-Orozco
    • 1
  • J. G. Hentz
    • 1
  1. 1.College of MedicineMayo ClinicScottsdaleUSA
  2. 2.College of Liberal Arts and SciencesArizona State UniversityTempeUSA

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