PDF icon Download PDF
Horm Metab Res 2010; 42(7): 467-482
DOI: 10.1055/s-0030-1252020
Review

© Georg Thieme Verlag KG Stuttgart · New York

Depression and Osteoporosis: A Research Synthesis with Meta-Analysis

G. Cizza1 , S. Primma1 , M. Coyle1 , L. Gourgiotis1 , G. Csako2
  • 1Clinical Endocrine Section, Clinical Endocrinology Branch, NIDDK, NIH, DHHS, Bethesda, MD, USA
  • 2Department of Laboratory Medicine, Clinical Center, NIH, DHHS, Bethesda, MD, USA
Further Information

Publication History

received 09.06.2009

accepted after second revision 08.03.2010

Publication Date:
07 May 2010 (online)

Also available ateRef
   Permissions and Reprints
Preview

Abstract

Major depressive disorder has been associated with low bone mineral density. The strength of this association, however, varies greatly among studies; the direction of the causative link is still controversial, and the etiology remains unclear. We aimed to confirm this association, assess its magnitude and estimate its clinical relevancy. A total of 535 articles were initially identified and the research synthesis was based on 33 qualified articles. Of these, 25 articles (or 76%) showed an inverse relationship between major depression or minor depression or depressive symptoms and bone mineral density or bone turnover. Meta-analysis could be performed on 20 of the initially selected 33 articles. Standardized weighted differences in mean AP spine, total femur and femoral neck bone mineral density, each from at least 10 studies, were computed in g/cm2 and transformed into percent differences. At each site, bone mass was lower in subjects with depression as compared to controls: AP spine bone mineral density was 4.73% lower (95% CI −7.28% to −2.19%, p<0.0001; n=16 studies), total femur bone mineral density was 3.53% lower (95% CI −5.66% to −1.41%, p<0.001; n=13 studies), and femoral neck bone mineral density was 7.32% lower (95% CI −10.67% to −3.96%; p<0.0005; n=8 studies). In conclusion, major depressive disorder was associated with lower bone mineral density at the AP spine, femoral neck, and total femur. The deficits in bone mineral density in subjects with depression are of clinical significance and likely to increase fracture risk over the lifetime of these subjects.

Key words

bone - fractures - stress - antidepressants - women - evidence-based medicine - leptin

References

  • 1 Evans DL, Charney DS, Lewis L, Golden RN, Gorman JM, Krishnan KR, Nemeroff CB, Bremner JD, Carney RM, Coyne JC, Delong MR, Frasure-Smith N, Glassman AH, Gold PW, Grant I, Gwyther L, Ironson G, Johnson RL, Kanner AM, Katon WJ, Kaufmann PG, Keefe FJ, Ketter T, Laughren TP, Leserman J, Lyketsos CG, McDonald WM, McEwen BS, Miller AH, Musselman D, O'Connor C, Petitto JM, Pollock BG, Robinson RG, Roose SP, Rowland J, Sheline Y, Sheps DS, Simon G, Spiegel D, Stunkard A, Sunderland T, Tibbits Jr P, Valvo WJ. Mood disorders in the medically ill: scientific review and recommendations.  Biol Psychiatry. 2005;  58 175-189
    Search in Google Scholar
  • 2 Cizza G, Ravn P, Chrousos GP, Gold PW. Depression: a major, unrecognized risk factor for osteoporosis?.  Trends Endocrinol Metab. 2001;  12 198-203
    Search in Google Scholar
  • 3 Anonymous. Management of osteoporosis in postmenopausal women: 2006 position statement of The North American Menopause Society.  Menopause. 2006;  13 340-367 ; quiz 368-349
    Search in Google Scholar
  • 4 Kristiansen C. Catching secondary causes of osteoporosis.  Endocrine News. 2006;  1
    Search in Google Scholar
  • 5 Altindag O, Altindag A, Asoglu M, Gunes M, Soran N, Deveci Z. Relation of cortisol levels and bone mineral density among premenopausal women with major depression.  Int J Clin Pract. 2007;  61 416-420
    Search in Google Scholar
  • 6 Diem SJ, Blackwell TL, Stone KL, Yaffe K, Haney EM, Bliziotes MM, Ensrud KE. Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures.  Arch Intern Med. 2007;  167 1240-1245
    Search in Google Scholar
  • 7 Eskandari F, Martinez PE, Torvik S, Phillips TM, Sternberg EM, Mistry S, Ronsaville D, Wesley R, Toomey C, Sebring NG, Reynolds JC, Blackman MR, Calis KA, Gold PW, Cizza G. Premenopausal, Osteoporosis Women, Alendronate, Depression (POWER) Study Group. Low bone mass in premenopausal women with depression.  Arch Intern Med. 2007;  167 2329-2336
    Search in Google Scholar
  • 8 Jacka FN, Pasco JA, Henry MJ. et al . Depression and bone mineral density in a community sample of perimenopausal women: Geelong Osteoporosis Study.  Menopause. 2005;  12 88-91
    Search in Google Scholar
  • 9 Konstantynowicz J, Kadziela-Olech H, Kaczmarski M, Kotowicz MA, Dodd S, Nicholson GC, Berk M. Depression in anorexia nervosa: a risk factor for osteoporosis.  J Clin Endocrinol Metab. 2005;  90 5382-5385
    Search in Google Scholar
  • 10 Ozsoy S, Esel E, Turan MT, Kula M, Demir H, Kartalci S, Kökbudak Z. [Is there any alteration in bone mineral density in patients with depression?].  Turk Psikiyatri Derg. 2005;  16 77-82
    Search in Google Scholar
  • 11 Wong SY, Lau EM, Lynn H, Leung PC, Woo J, Cummings SR, Orwoll E. Depression and bone mineral density: is there a relationship in elderly Asian men?.  Results from Mr. Os (Hong Kong). Osteoporos Int. 2005;  16 610-615
    Search in Google Scholar
  • 12 Yazici AE, Bagis S, Tot S, Sahin G, Yazici K, Erdogan C. Bone mineral density in premenopausal women with major depression.  Joint Bone Spine. 2005;  72 540-543
    Search in Google Scholar
  • 13 Mussolino ME, Jonas BS, Looker AC. Depression and bone mineral density in young adults: results from NHANES III.  Psychosom Med. 2004;  66 533-537
    Search in Google Scholar
  • 14 Petronijevic MR, Ivkovic M, Paunovic VR, Glisic BC, Petronijevic ND, Stefanovic DZ. Chronic depression as risk factor for osteoporosis.  Osteoporosis International. 2004;  15 S80
    Search in Google Scholar
  • 15 Whooley MA, Cauley JA, Zmuda JM, Haney EM, Glynn NW. Depressive symptoms and bone mineral density in older men.  J Geriatr Psychiatry Neurol. 2004;  17 88-92
    Search in Google Scholar
  • 16 Thomas PD, A; Thomas, CH. Depression and osteoporosis. Measurements by femoral dual energy absorptiometry in elderly patients with or without depression.  Age and Nutrition. 2003;  14 17-23
    Search in Google Scholar
  • 17 Yazici KM, Akinci A, Sutcu A, Ozcakar L. Bone mineral density in premenopausal women with major depressive disorder.  Psychiatry Res. 2003;  117 271-275
    Search in Google Scholar
  • 18 Kavuncu V, Kuloglu M, Kaya A, Sahin S, Atmaca M, Firidin B. metabolism and bone mineral density in premenopausal women with mild depression.  Yonsei Med J. 2002;  43 101-108
    Search in Google Scholar
  • 19 Robbins J, Hirsch C, Whitmer R, Cauley J, Harris T. The association of bone mineral density and depression in an older population.  J Am Geriatr Soc. 2001;  49 732-736
    Search in Google Scholar
  • 20 Reginster JY, Deroisy R, Paul I, Hansenne M, Ansseau M. Depressive vulnerability is not an independent risk factor for osteoporosis in postmenopausal women.  Maturitas. 1999;  33 133-137
    Search in Google Scholar
  • 21 Whooley MA, Kip KE, Cauley JA, Ensrud KE, Nevitt MC, Browner WS. Depression, falls, and risk of fracture in older women. Study of Osteoporotic Fractures Research Group.  Arch Intern Med. 1999;  159 484-490
    Search in Google Scholar
  • 22 Amsterdam JD, Hooper MB. Bone density measurement in major depression.  Prog Neuropsychopharmacol Biol Psychiatry. 1998;  22 267-277
    Search in Google Scholar
  • 23 Michelson D, Stratakis C, Hill L, Reynolds J, Galliven E, Chrousos G, Gold P. mineral density in women with depression.  N Engl J Med. 1996;  335 1176-1181
    Search in Google Scholar
  • 24 Schweiger U, Deuschle M, Korner A, Lammers CH, Schmider J, Gotthardt U, Holsboer F, Heuser I. Low lumbar bone mineral density in patients with major depression.  Am J Psychiatry. 1994;  151 1691-1693
    Search in Google Scholar
  • 25 Dorn LD, Susman EJ, Pabst S, Huang B, Kalkwarf H, Grimes S. Association of depressive symptoms and anxiety with bone mass and density in ever-smoking and never-smoking adolescent girls.  Arch Pediatr Adolesc Med. 2008;  162 1181-1188
    Search in Google Scholar
  • 26 Petronijevic M, Petronijevic N, Ivkovic M, Stefanoviæ D, Radonjiæ N, Glisiæ B, Ristiæ G, Damjanoviæ A, Paunoviæ V. bone mineral density and high bone metabolism turnover in premenopausal women with unipolar depression.  Bone. 2008;  42 582-590
    Search in Google Scholar
  • 27 Diem SJ, Blackwell TL, Stone KL, Yaffe K, Cauley JA, Whooley MA, Ensrud KE. Study of Osteoporotic Fractures. Depressive symptoms and rates of bone loss at the hip in older women.  J Am Geriatr Soc. 2007;  55 824-831
    Search in Google Scholar
  • 28 Niti M, Ng TP, Kua EH, Ho RC, Tan CH. Depression and chronic medical illnesses in Asian older adults: the role of subjective health and functional status.  Int J Geriatr Psychiatry. 2007;  22 1087-1094
    Search in Google Scholar
  • 29 Silverman SL, Shen W, Minshall ME, Xie S, Moses KH. Prevalence of depressive symptoms in postmenopausal women with low bone mineral density and/or prevalent vertebral fracture: results from the Multiple Outcomes of Raloxifene Evaluation (MORE) study.  J Rheumatol. 2007;  34 140-144
    Search in Google Scholar
  • 30 Tolea MI, Black SA, Carter-Pokras OD, Kling MA. Depressive symptoms as a risk factor for osteoporosis and fractures in older Mexican American women.  Osteoporos Int. 2007;  18 315-322
    Search in Google Scholar
  • 31 Kahl KG, Greggersen W, Rudolf S, Stoeckelhuber BM, Bergmann-Koester CU, Dibbelt L, Schweiger U. mineral density, bone turnover, and osteoprotegerin in depressed women with and without borderline personality disorder.  Psychosom Med. 2006;  68 669-674
    Search in Google Scholar
  • 32 Korpelainen R, Korpelainen J, Heikkinen J, Vaananen K, Keinanen-Kiukaanniemi S. Lifelong risk factors for osteoporosis and fractures in elderly women with low body mass index--a population-based study.  Bone. 2006;  39 385-391
    Search in Google Scholar
  • 33 Bianchi ML, Orsini MR, Saraifoger S, Ortolani S, Radaelli G, Betti S. Quality of life in post-menopausal osteoporosis.  Health Qual Life Outcomes. 2005;  3 78
    Search in Google Scholar
  • 34 Cankurtaran M, Halil M, Yavuz BB, Dagli N, Cankurtaran ES, Ariogul S. and concomitant diseases in a Turkish geriatric outpatient setting.  Arch Gerontol Geriatr. 2005;  40 307-315
    Search in Google Scholar
  • 35 Kahl KG, Rudolf S, Dibbelt L, Stoeckelhuber BM, Gehl HB, Hohagen F, Schweiger U. Decreased osteoprotegerin and increased bone turnover in young female patients with major depressive disorder and a lifetime history of anorexia nervosa.  Osteoporos Int. 2005;  16 424-429
    Search in Google Scholar
  • 36 Mussolino ME. Depression and hip fracture risk: the NHANES I epidemiologic follow-up study.  Public Health Rep. 2005;  120 71-75
    Search in Google Scholar
  • 37 Schweiger U, Weber B, Deuschle M, Heuser I. Lumbar bone mineral density in patients with major depression: evidence of increased bone loss at follow-up.  Am J Psychiatry. 2000;  157 118-120
    Search in Google Scholar
  • 38 Egger M, Smith GD, Phillips AN. Meta-analysis: principles and procedures.  BMJ. 1997;  315 1533-1537
    Search in Google Scholar
  • 39 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses.  BMJ. 2003;  327 557-560
    Search in Google Scholar
  • 40 Chalmers TC, Smith Jr H, Blackburn B, Silverman B, Schroeder B, Reitman D, Ambroz A. A method for assessing the quality of a randomized control trial.  Control Clin Trials. 1981;  2 31-49
    Search in Google Scholar
  • 41 Syed Z, Khan A. Bone densitometry: applications and limitations.  J Obstet Gynaecol Can. 2002;  24 476-484
    Search in Google Scholar
  • 42 Forsen L, Meyer HE, Sogaard AJ, Naess S, Schei B, Edna TH. Mental distress and risk of hip fracture. Do broken hearts lead to broken bones?.  J Epidemiol Community Health. 1999;  53 343-347
    Search in Google Scholar
  • 43 Greendale GA, Unger JB, Rowe JW, Seeman TE. The relation between cortisol excretion and fractures in healthy older people: results from the MacArthur studies-Mac.  J Am Geriatr Soc. 1999;  47 799-803
    Search in Google Scholar
  • 44 Sogaard AJ, Joakimsen RM, Tverdal A, Fønnebø V, Magnus JH, Berntsen GK. Long-term mental distress, bone mineral density and non-vertebral fractures.  The Tromso Study. Osteoporos Int. 2005;  16 887-897
    Search in Google Scholar
  • 45 Milliken LA, Wilhelmy J, Martin CJ. et al . 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. 2006;  61 488-494
    Search in Google Scholar
  • 46 Ward KD, Klesges RC. A meta-analysis of the effects of cigarette smoking on bone mineral density.  Calcif Tissue Int. 2001;  68 259-270
    Search in Google Scholar
  • 47 Bonaiuti D, Shea B, Iovine R, Negrini S, Robinson V, Kemper HC, Wells G, Tugwell P, Cranney A. Exercise for preventing and treating osteoporosis in postmenopausal women.  Cochrane Database Syst Rev. 2002;  CD000333
    Search in Google Scholar
  • 48 Shea B, Bonaiuti D, Iovine R, Negrini S. Cochrane Review on exercise for preventing and treating osteoporosis in postmenopausal women.  Eura Medicophys. 2004;  40 199-209
    Search in Google Scholar
  • 49 Siris ES, Brenneman SK, Barrett-Connor E, Miller PD, Sajjan S, Berger ML, Chen YT. effect of age and bone mineral density on the absolute, excess, and relative risk of fracture in postmenopausal women aged 50–99: results from the National Osteoporosis Risk Assessment (NORA).  Osteoporos Int. 2006;  17 565-574
    Search in Google Scholar
  • 50 Wu Q, Magnus JH, Liu J, Bencaz AF, Hentz JG. Depression and low bone mineral density: a meta-analysis of epidemiologic studies.  Osteoporos Int. 2009;  20 1309-1320
    Search in Google Scholar
  • 51 Yirmiya R, Bab I. Major depression is a risk factor for low bone mineral density: a meta-analysis.  Biol Psychiatry. 2009;  66 423-432
    Search in Google Scholar
  • 52 Cizza G, Primma S, Csako G. Depression as a risk factor for osteoporosis.  Trends Endocrinol Metab. 2009;  20 367-373
    Search in Google Scholar
  • 53 Yirmiya R, Goshen I, Bajayo A, Kreisel T, Feldman S, Tam J, Trembovler V, Csernus V, Shohami E, Bab I. Depression induces bone loss through stimulation of the sympathetic nervous system.  Proc Natl Acad Sci U S A. 2006;  103 16876-16881
    Search in Google Scholar
  • 54 Muhsen K, Lipsitz J, Garty-Sandalon N, Gross R, Green MS. Correlates of generalized anxiety disorder: independent of co-morbidity with depression: findings from the first Israeli National Health Interview Survey (2003–2004).  Soc Psychiatry Psychiatr Epidemiol. 2008;  43 898-904
    Search in Google Scholar
  • 55 Siervo M, Wells JC, Cizza G. The contribution of psychosocial stress to the obesity epidemic: an evolutionary approach.  Horm Metab Res. 2009;  41 261-270
    Search in Google Scholar
  • 56 Fukumoto S, Martin TJ. Bone as an endocrine organ.  Trends Endocrinol Metab. 2009;  20 230-236
    Search in Google Scholar
  • 57 Mezuk B, Eaton WW, Golden SH, Ding Y. The influence of educational attainment on depression and risk of type 2 diabetes.  Am J Public Health. 2008;  98 1480-1485
    Search in Google Scholar
  • 58 Pittas AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B. Association between serum osteocalcin and markers of metabolic phenotype.  J Clin Endocrinol Metab. 2009;  94 827-832
    Search in Google Scholar
  • 59 Kanazawa I, Yamaguchi T, Yamamoto M. et al . Serum osteocalcin level is associated with glucose metabolism and atherosclerosis parameters in type 2 diabetes mellitus.  J Clin Endocrinol Metab. 2009;  94 45-49
    Search in Google Scholar
  • 60 Blake GM, Fogelman I. The clinical role of dual energy X-ray absorptiometry.  Eur J Radiol. 2009; 
    Search in Google Scholar
  • 61 Lowe B, Spitzer RL, Grafe K. et al . Comparative validity of three screening questionnaires for DSM-IV depressive disorders and physicians' diagnoses.  J Affect Disord. 2004;  78 131-140
    Search in Google Scholar
  • 62 Alexander JL, Richardson G, Grypma L, Hunkeler EM. Collaborative depression care, screening, diagnosis and specificity of depression treatments in the primary care setting.  Expert Rev Neurother. 2007;  7 S59-80
    Search in Google Scholar
  • 63 Fischer-Posovszky P, Wabitsch M, Hochberg Z. Endocrinology of adipose tissue - an update.  Horm Metab Res. 2007;  39 314-321
    Search in Google Scholar

Correspondence

G. CizzaMD, PhD, MHSc 

Building 10, CRC, Rm. 6-3940

MD 20892-1613 Bethesda

USA

Phone: +1/301/496 87 11

Fax: +1/301/480 20 47

Email: cizzag@intra.niddk.nih.gov