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Osteoporosis International

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01-01-2008 | Review

Depression and osteoporosis: epidemiology and potential mediating pathways

Authors: B. Mezuk, W. W. Eaton, S. H. Golden

Published in: Osteoporosis International | Issue 1/2008

Abstract

Introduction

There have been numerous studies examining the association between depression and bone mineral density (BMD), but the underlying nature of this relationship remains unclear. Independent of this association, there is a growing body of evidence that depression impacts the risk for fracture in older adults. This article reviews the current epidemiological evidence regarding comorbidity of depression, low bone mineral density, and fracture.

Methods

A review of the literature on depression, depressive symptoms, low BMD, osteoporosis, and fracture using electronic databases.

Results

We reviewed 20 studies of the association between depression and BMD and five reports of the relationship between depression and fractures. Potential mediating mechanisms (both physiological and behavioral) are discussed, as well as potential confounding influences (e.g., medication use).

Conclusions

Most studies support the finding that depression is associated with increased risk for both low BMD and fractures, but variation in study design, sample composition, and exposure measurement make comparisons across studies difficult. Researchers should be aware of potential confounders, such as medication use, that may influence results. Future research should focus on identifying mediating pathways and targets for intervention in the relationships between depression, low BMD, and fracture.

Albright F (1947) Osteoporosis. Ann Intern Med 27:861–882PubMed

Takkouche B, Montes-Martinez A, Gill S et al (2007) Psychotropic medications and the risk of fracture: a meta-analysis. Drug Safety 30:171–184PubMedCrossRef

Cizza G, Ravn P, Chrousos G (2001) Depression: a major, unrecognized risk factor for osteoporosis? Trends Endocrinol Metab 12:198–203PubMedCrossRef

Kessler R, Berglund P, Delmer O et al (2005) Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 62:593–602PubMedCrossRef

Evans D, Charney D, Lewis L et al (2005) Mood disorders in the medically ill: scientific review and recommendations. Biol Psychiatry 58:175–189PubMedCrossRef

Schweiger U, Deuschle M, Korner A et al (1994) Low lumbar bone mineral density in patients with major depression. Am J Psychiatry 151:1691–1693PubMed

Coelho R, Silva C, Maia A et al (1999) Bone mineral density and depression: a community study of women. J Psychosom Res 46:29–35PubMedCrossRef

Halbreich U, Rojansky N, Palter S et al (1995) Decreased bone mineral density in medicated psychiatric patients. Psychosom Med 57:485–491PubMed

Jacka F, Pasco J, Henry M et al (2005) Depression and bone mineral density in a community setting of perimenopausal women: Geelong Osteoporosis Study. Menopause 12:88–91PubMedCrossRef

10.

Kahl K, Rudolf S, Stoeckelhuber B et al (2005) Bone mineral density, markers of bone turnover, and cytokines in young women with borderline personality disorder with and without comorbid major depressive disorder. Am J Psychiatry 162:168–174PubMedCrossRef

11.

Michelson D, Stratakis C, Hill L et al (1996) Bone mineral density in women with depression. NEJM 335:1176–1181PubMedCrossRef

12.

Robbins J, Hirsch C, Whitmer R et al (2001) The association of bone mineral density and depression in an older population. J Am Geriatr Soc 49:732–736PubMedCrossRef

13.

Schweiger U, Weber B, Meuschle M et al (2000) Lumbar bone mineral density in patients with major depression: evidence of increased bone loss at followup. Am J Psychiatry 157:118–120PubMed

14.

Vrkljan M, Thaller V, Lovricevic I et al (2001) Depressive disorder as a possible risk factor for osteoporosis. Coll Antropol 25:485–492PubMed

15.

Wong S, Lau E, Lynn H et al (2005) Depression and bone mineral density: is there a relationship in elderly Asian men? Results from Mr. Os (Hong Kong). Osteoporos Int 16:610–615PubMedCrossRef

16.

Yazici K, Akinci A, Sutcu A et al (2003) Bone mineral density in premenopausal women with major depressive disorder. Psychiatry Res 117:271–275PubMedCrossRef

17.

Altindag O, Altindag A, Asoglu M et al (2007) Relation of cortisol levels and bone mineral density among premenopausal women with major depression. Int J Clin Pract 61:416–420PubMedCrossRef

18.

Mussolino M, Jonas B, Looker A (2004) Depression and bone mineral density in young adults: results from NHANES III. Psychosom Med 66:533–537PubMedCrossRef

19.

Sogaard A, Joakimsen R, Tverdal A et al (2005) Long-term mental distress, bone mineral density and non-vertebral factures: the Tromso Study. Osteoporos Int 16:887–897PubMedCrossRef

20.

Amsterdam J, Hooper M (1998) Bone mineral density in major depression. Prog Neuro-Psychopharmacol Biol Psychiatry 22:267–277CrossRef

21.

Kavuncu V, Kuloglu M, Kaya A et al (2002) Bone metabolism and bone mineral density in premenopausal women with mild depression. Yonsei Med J 43:101–108PubMed

22.

Reginster J, Deroisy R, Paul I et al (1999) Depressive vulnerability is not an independent risk factor for osteoporosis in post-menopausal women. Maturitas 33:133–137PubMedCrossRef

23.

Whooley M, Cauley J, Zmuda J et al (2004) Depressive symptoms and bone mineral density in men. J Geriatr Psychiatry Neurol 17:88–92PubMedCrossRef

24.

Whooley M, Kip K, Cauley J et al (1999) Depression, falls and risk of fracture in older women. Arch Intern Med 159:484–490PubMedCrossRef

25.

Yazici A, Bagis S, Tot S et al (2005) Bone mineral density in premenopausal women with major depression. Joint Bone Spine 72:540–543PubMedCrossRef

26.

Berkson J (1946) Limitations of the application of fourfold table analysis to hospital data. Biometrics 2:47–53CrossRef

27.

Eaton WW, Anthony J, Gallo J et al (1997) Natural history of Diagnostic Interview Schedule/DSM-IV major depression: the Baltimore Epidemiologic Catchment Area followup. Arch Gen Psych 54:993–999

28.

Copeland K, Checkoway H, McMichael A et al (1977) Bias due to misclassification in the estimation of relative risk. Am J Epidemiol 105:488–495PubMed

29.

Forsen L, Sogaard A, Meyer H et al (1999) Survival after hip fracture: short and long-term excess mortality according to age and gender. Osteoporos Int 10:73–78PubMedCrossRef

30.

Kelsey J, Prill M, Keegan T et al (2005) Reducing the risk of distal forearm fracture: preserve bone mass, slow down and don't fall! Osteoporos Int 16:681–690PubMedCrossRef

31.

Greendale G, Unger J, Rowe J et al (1999) The relation between cortisol excretion and fractures in healthy older people: results from the MacArthur Studies. J Am Geriatr Soc 47:799–803PubMed

32.

Mussolino M (2005) Depression and hip fracture: the NHANES I Epidemiologic followup study. Public Health Rep 120:71–75PubMed

33.

Forsen L, Meyer H, Sogaard A et al (1999) Mental distress and risk of hip fracture: do broken hearts lead to broken bones? J Epidemiol Community Health 53:343–347PubMed

34.

Carroll B, Curtis G, Davies B et al (1976) Urinary free cortisol excretion in depression. Psychol Med 6:43–50PubMedCrossRef

35.

World Health Organization (1994) Assessment of fracture risk and its application to screening for post-menopausal osteoporosis: report of the WHO study group. World Health Organ Tech Rep Ser 843:1–126

36.

Korpelainen R, Korpelainen J, Heikkinen J et al (2006) Lifelong risk factors for osteoporosis and fractures in elderly women with low body mass index-a population-based study. Bone 39:385–391PubMedCrossRef

37.

Shoback D, Marcus R, Bikle D (2004) Metabolic Bone Disease. In Greenspan F, Gardner D (eds) Basic and clinical endocrinology. Lange Medical Books/McGraw-Hill, New York, pp 295–361

38.

Raisz L (1999) Physiology and pathophysiology of bone remodeling. Clin Chem 48:1353–1358

39.

Kann P, Laudes M, Piepkorn B et al (2001) Suppressed levels of serum cortisol following high-dose oral dexamethasone administration differ between healthy postmenopausal females and patients with established primary vertebral osteoporosis. Clin Rheumatol 20:25–29PubMedCrossRef

40.

Licinio J, Wong M (1999) The role of inflammatory mediators in the biology of major depression: central nervous system cytokines modulate the biological substrate of depressive symptoms, regulate stress-response systems, and contribute to neurotoxicity and neuroprotection. Mol Psychiatry 4:317–327PubMedCrossRef

41.

Ganesan K, Teklehaimanot S, Tran T et al (2005) Relationship of c-reactive protein and bone mineral density in community-dwelling elderly females. J Natl Med Assoc 97:329–333PubMed

42.

Papanicolaou D, Wilder R, Manolagas S et al (1998) The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med 128:127–137PubMed

43.

Lake C, Pickar D, Ziegler M et al (1982) High plasma norepinephrine levels in patients with major affective disorder. Am J Psychiatry 139:1315–1318PubMed

44.

Maes M, Vandewoude M, Schotte C et al (1990) Positive relationship between the catecholaminergic turnover and the DST results in depression. Psychol Med 20:493–499PubMedCrossRef

45.

Winokur A, Maislin G, Phillips J et al (1988) Insulin resistance after oral glucose tolerance testing in patients with major depression. Am J Psychiatry 145:325–330PubMed

46.

Thrailkill K, Lumpkin C, Bunn R-C et al (2005) Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues. Am J Physiol Endocrinol Metab 289:735–745

47.

Rehman H, Masson E (2005) Neuroendocrinology of female aging. Gend Med 2:41–56PubMedCrossRef

48.

Carnahan R, Perry P (2004) Depression in aging men: the role of testosterone. Drugs Aging 21:361–376PubMedCrossRef

49.

Khosla S, Melton LJ 3rd, O’Fallon W et al (1998) Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J Clin Endocrinol Metab 83:2266–2274PubMedCrossRef

50.

Herran A, Amado J, Garcia-Unzueta M et al (2000) Increased bone remodeling in first-episode major depressive disorder. Psychosom Med 62:779–782PubMed

51.

Kanis J (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. Osteoporos Int 4:368–381PubMedCrossRef

52.

Anda R, Williamson D, Escobedo L et al (1990) Depression and the dynamics of smoking: a national perspective. JAMA 264:1541–1545PubMedCrossRef

53.

Kapoor D, Jones T (2005) Smoking and hormones in health and endocrine disorders. Eur J Endocrinol 152:491–499PubMedCrossRef

54.

Grant B, Harford T (1995) Comorbidity between DSM-IV alcohol use disorders and major depression: results of a national survey. Drug Alcohol Depend 39:197–206PubMedCrossRef

55.

Chakkalakal D (2005) Alcohol-induced bone loss and deficient bone repair. Alcohol Clin Exp Res 29:2077–2090PubMedCrossRef

56.

Friday K, Howard G (1991) Ethanol inhibits human bone cell proliferation and function in vitro. Metabolism 40:562–565PubMedCrossRef

57.

Camancho T, Roberts R, Lazarus N et al (1991) Physical activity and depression: evidence from the Alameda County Study. Am J Epidemiol 134:220–231

58.

Kritz-Silverstein D, Barrett-Connor E, Corbeau C (2001) Cross-sectional and prospective study of exercise and depressed mood in the elderly: the Rancho Bernardo Study. Am J Epidemiol 153:596–603PubMedCrossRef

59.

Heo M, Pietrobelli A, Fontaine K et al (2006) Depressive mood and obesity in US adults: comparison and moderation by sex, age and race. Int J Obes 30:513–519CrossRef

60.

Weber-Hamann B, Hentschel F, Kniest A et al (2002) Hypercortisolemic depression is associated with increased intra-abdominal fat. Psychosom Med 64:274–277PubMed

61.

Bjorntorp P (1992) Abdominal fat distribution and disease: an overview of epidemiological data. Ann Med 24:15–18PubMedCrossRef

62.

Dargent-Molina P, Poitiers F, Breart G (2000) In elderly women weight is the best predictor of a very low bone mineral density: evidence from the EPIDOS study. Osteoporos Int 11:881–888PubMedCrossRef

63.

Schiff I (1995) Menopause. In Becker K (ed) Principles and practice of endocrinology and metabolism. J.B. Lippincott Company, Philadelphia, PA, pp 915–924

64.

Bjorntorp P, Rosmond R (1999) Hypothalamic origin of the metabolic syndrome X. Ann NY Acad Sci 18:297–307CrossRef

65.

Ljung T, Holm G, Friberg P et al (2000) The activity of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system in relation to waist/hip circumference ratio in men. Obes Res 8:487–495PubMedCrossRef

66.

Anderson R, Freedland K, Clouse R et al (2001) The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care 24:1069–1078PubMedCrossRef

67.

Sert M, Tetiker T, Kirim S et al (2003) Type 2 diabetes mellitus and osteopenia: is there an association? Acta Diabetol 40:105–108PubMed

68.

Kao W, Krammerer C, Schneider J et al (2003) Type 2 diabetes is associated with increased bone mineral density in Mexican-American women. Arch Med Res 34:399–406PubMedCrossRef

69.

de Liefde I, van der Klift M, de Laet C et al (2005) Bone mineral density and fracture risk in type 2 diabetes mellitus: the Rotterdam Study. Osteoporos Int 16:1713–1720PubMedCrossRef

70.

Lopez-Ibarra P, Pastor M, Escobar-Jimenez F et al (2001) Bone mineral density and time of clinical diagnosis of adult-onset type 1 diabetes mellitus. Endocr Pract 7:346–351PubMed

71.

Forsen L, Meyer H, Midthjell K et al (1999) Diabetes mellitus and the incidence of hip fracture: results from the Nord-Trondelag Health Survey. Diabetologia 42:920–925PubMedCrossRef

72.

Vestergaard P, Rejnmark L, Mosekilde L (2005) Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia 48:1292–1299PubMedCrossRef

73.

Vestergaard P (2005) Epilepsy, osteoporosis and fracture risk-a meta-analysis. Acta Neurol Scand 112:277–286PubMedCrossRef

74.

Hela S, Nihel M, Faten L et al (2005) Osteoporosis and Crohn′s disease. Joint Bone Spine 72:403–407PubMedCrossRef

75.

Romas E (2005) Bone loss in inflammatory arthritis: mechanisms and therapeutic approaches with biophosphonates. Best Pract Res Clin Rheumatol 19:1065–1079PubMedCrossRef

76.

Bertoli A, Alarcon G, Calvo-Alen M et al (2006) Systemic lupus erythematosus in a multiethnic US cohort: clinical features, course and outcome in patients with late-onset disease. Arthritis Rheum 54:1580–1587PubMedCrossRef

77.

Harpavat M, Keljo D, Reguerio M (2004) Metabolic bone disease in inflammatory bowel disease. J Clin Gastroenterol 38:218–224PubMedCrossRef

78.

Misra M, Papakostas G, Klibanski A (2004) Effects of psychiatric disorders and psychotropic medications on prolactin and bone metabolism. J Clin Psychiatry 65:1607–1618PubMedCrossRef

79.

Kinjo M, Setoguchi S, Schneeweiss S et al (2005) Bone mineral density in subjects using central nervous system-active medications. Am J Med 118:1414.e7–1414.e12CrossRef

80.

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

81.

Rejnmark L, Olsen M, Johnsen S et al (2004) Hip fracture risk in statin users-a population-based Danish case-control study. Osteoporos Int 15:452–458PubMed

82.

Kinoshita H, Kobayashi S, Ebara S et al (2000) Phosphodiesterase inhibitors, pentoxifylline and rolipram, increase bone mass mainly by promoting bone formation in normal mice. Bone 27:811–817PubMedCrossRef

83.

Waki Y, Horita T, Miyamoto K-I et al (1999) Effects of XT-44, a phosphodiesterase 4 inhibitor, in osteoblastgenesis and osteoclastgenesis in culture and its therapeutic effects in rat osteopenia models. Jpn J Pharmacol 79:477–483PubMedCrossRef

84.

Bliziotes M, Gunness M, Eshleman A et al (2002) The role of dopamine and serotonin in regulating bone mass and strength: studies on dopamine and serotonin transporter null mice. J Musculoskele Neuronal Interact 2:291–295

85.

Warden S, Robling A, Sanders M et al (2005) Inhibition of the serotonin (5-hydroxytryptamine) transporter reduces bone accrual during growth. Endocrinology 146:685–693PubMedCrossRef

86.

Battaglino R, Vokes M, Schulze-Spate U et al (2007) Fluoxetine treatment increases trabecular bone formation in mice. J Cell Biochem 100:1387–1394PubMedCrossRef

87.

Bonnet N, Bernard P, Beaupied H et al (2007) Various effects of antidepressant drugs on bone microarchitecture, mechanical properties and bone remodeling. Toxicol Applied Pharmacol 221:111–118CrossRef

88.

Cauley J, Fullman R, Stone K et al (2005) Factors associated with the lumbar spine and proximal femur bone mineral density in older men. Osteoporos Int 16:1525–1537PubMedCrossRef

89.

Diem S, Blackwell T, Stone K et al (2007) Use of antidepressants and rates of hip bone loss in older women. Arch Intern Med 167:1240–1245PubMedCrossRef

90.

Haney E, Chan B, Diem S et al (2007) Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med 167:1246–1251PubMedCrossRef

91.

Richards J, Papaioannou A, Adachi J et al (2007) Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med 167:188–194PubMedCrossRef

92.

Ensrud K, Blackwell T, Mangione C et al (2003) Central nervous system active medications and risk for fractures in older women. Arch Intern Med 163:949–957PubMedCrossRef

93.

Liu B, Anderson G, Mittmann N et al (1998) Use of selective serotonin reuptake inhibitors or tricyclic antidepressants and risk of hip fractures in elderly people. Lancet 351:1303–1307PubMedCrossRef

94.

Hubbard R, Farrington P, Smith C et al (2003) Exposure to tricyclic and selective serotonin reuptake inhibitor antidepressants and the risk of hip fracture. Am J Epidemiol 158:77–84PubMedCrossRef

95.

Thapa P, Gideon P, Cost T et al (1998) Antidepressants and the risk of falls among nursing home residents. NEJM 339:875–882PubMedCrossRef

96.

Svensson T (2000) Brain noradrenaline and the mechanisms of action of antidepressant drugs. Acta Psychiatr Scand Suppl 402:18–27PubMedCrossRef

Title: Depression and osteoporosis: epidemiology and potential mediating pathways
Authors: B. Mezuk
W. W. Eaton
S. H. Golden
Publication date: 01-01-2008
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 1/2008
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-007-0449-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Depression and osteoporosis: epidemiology and potential mediating pathways

Abstract

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

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