Subscribe to RSS
DOI: 10.1055/s-0030-1252020
© Georg Thieme Verlag KG Stuttgart · New York
Depression and Osteoporosis: A Research Synthesis with Meta-Analysis
Publication History
                     received 09.06.2009
                     
                     accepted after second revision 08.03.2010
                     
Publication Date:
07 May 2010 (online)

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 
            
            Reference Ris Wihthout Link
- 2 
            Cizza G, Ravn P, Chrousos GP, Gold PW. 
            Depression: a major, unrecognized risk factor for osteoporosis?. 
            Trends Endocrinol Metab. 
            2001; 
            12 
            198-203 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 4 
            Kristiansen C. 
            Catching secondary causes of osteoporosis. 
            Endocrine News. 
            2006; 
            1 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 22 
            Amsterdam JD, Hooper MB. 
            Bone density measurement in major depression. 
            Prog Neuropsychopharmacol Biol Psychiatry. 
            1998; 
            22 
            267-277 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 36 
            Mussolino ME. 
            Depression and hip fracture risk: the NHANES I epidemiologic follow-up study. 
            Public Health Rep. 
            2005; 
            120 
            71-75 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 38 
            Egger M, Smith GD, Phillips AN. 
            Meta-analysis: principles and procedures. 
            BMJ. 
            1997; 
            315 
            1533-1537 
            
            Reference Ris Wihthout Link
- 39 
            Higgins JP, Thompson SG, Deeks JJ, Altman DG. 
            Measuring inconsistency in meta-analyses. 
            BMJ. 
            2003; 
            327 
            557-560 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 41 
            Syed Z, Khan A. 
            Bone densitometry: applications and limitations. 
            J Obstet Gynaecol Can. 
            2002; 
            24 
            476-484 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 52 
            Cizza G, Primma S, Csako G. 
            Depression as a risk factor for osteoporosis. 
            Trends Endocrinol Metab. 
            2009; 
            20 
            367-373 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 56 
            Fukumoto S, Martin TJ. 
            Bone as an endocrine organ. 
            Trends Endocrinol Metab. 
            2009; 
            20 
            230-236 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 60 
            Blake GM, Fogelman I. 
            The clinical role of dual energy X-ray absorptiometry. 
            Eur J Radiol. 
            2009; 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 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 
            
            Reference Ris Wihthout Link
- 63 
            Fischer-Posovszky P, Wabitsch M, Hochberg Z. 
            Endocrinology of adipose tissue - an update. 
            Horm Metab Res. 
            2007; 
            39 
            314-321 
            
            Reference Ris Wihthout Link
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
         
         
 
     
      
    