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Depressive Symptoms, Bone Loss, and Fractures in Postmenopausal Women

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Abstract

Background

Osteoporosis and depression may be associated through common physiologic systems or risk factors.

Objective

To assess the associations between depressive symptoms (Burnam’s scale) or antidepressant use and bone outcomes.

Design

Prospective cohort study.

Participants

A total of 93,676 postmenopausal women (50 to 79 years old) enrolled in the Women’s Health Initiative Observational Study.

Measurements

Self-reported fractures (n = 14,982) (hip [adjudicated], spine, wrist, and “other”). Analyses included 82,410 women with complete information followed on average for 7.4 years. Bone mineral density (BMD) of the hip (n = 4539), spine (n = 4417), and whole body (n = 4502) was measured at baseline and 3 years in women enrolled at 3 densitometry study sites.

Results

Overall, there were no statistically significant associations between depressive symptoms or antidepressant therapy and 3-year change in BMD. In a subset of women not using antidepressants, there was a significant difference in whole-body BMD change between women with and without depressive symptoms (P = .05). Depressive symptoms (hazard ratio [HR] 1.08; 95% CI = 1.02 to 1.14) and antidepressant therapy (HR = 1.22; CI = 1.15 to 1.30) independently increased risk of any fracture, the majority of which occurred at “other” anatomic sites. Antidepressant therapy increased the risk of spine fracture (HR = 1.36; CI = 1.14 to 1.63). No associations were observed between depressive symptoms or antidepressant therapy and hip or wrist fracture.

Conclusion

In this study of postmenopausal women, average age 64, we observed minimal association between depressive symptoms and 3-year changes in either BMD or fracture risk. Antidepressant use was not associated with changes in BMD, but was associated with increased risk of fractures at the spine and “other ” anatomic sites.

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References

  1. National Osteoporosis Foundation. NOF Advocacy — The State of Osteoporosis and Low Bone Mass in the US. Available at: http://www.nof.org/advocacy/prevalence/. Accessed January 18, 2008.

  2. Hasin DS, Goodwin RD, Stinson FS, Grant BF. Epidemiology of major depressive disorder: results from the National Epidemiologic Survey on Alcoholism and Related Conditions. Arch Gen Psychiatry. 2005;62:1097–106.

    Article  PubMed  Google Scholar 

  3. Murphy BE. Steroids and depression. J Steroid Biochem Mol Biol. 1991;38:537–59.

    Article  PubMed  CAS  Google Scholar 

  4. Swaab DF, Bao AM, Lucassen PJ. The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev. 2005;4:141–94.

    Article  PubMed  CAS  Google Scholar 

  5. Schiepers OJ, Wichers MC, Maes M. Cytokines and major depression. Prog Neuro-psychopharmacol Biol Psychiatry. 2005;29:201–17.

    Article  CAS  Google Scholar 

  6. Eskandari F, Martinez PE, Torvik S, et al. Low bone mass in premenopausal women with depression. Arch Intern Med. 2007;167(21)2329–36.

    Article  PubMed  Google Scholar 

  7. Hofbauer LC, Khosla S, Dunstan C, Lacey DL, Boyle WJ, Riggs BL. The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Miner Res. 2000;15:2–12.

    Article  PubMed  CAS  Google Scholar 

  8. Kahl KG, Rudolf S, Stoeckelhuber BM, et al. 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. 2005;162:168–74.

    Article  PubMed  Google Scholar 

  9. Warden SJ, Bliziotes MM, Wiren KM, Eshleman AJ, Turner CH. Neural regulation of bone and the skeletal effects of serotonin (5-hydroxytryptamine). Mol Cell Endocrinol. 2005;242:1–9.

    Article  PubMed  CAS  Google Scholar 

  10. Bliziotes M, Eshleman A, Burt-Pichat B, et al. Serotonin transporter and receptor expression in osteocytic MLO-Y4 cells. Bone. 2006;39:1313–21.

    Article  PubMed  CAS  Google Scholar 

  11. Bliziotes MM, Eshleman AJ, Zhang XW, Wiren KM. Neurotransmitter action in osteoblasts: expression of a functional system for serotonin receptor activation and reuptake. Bone. 2001;29:477–86.

    Article  PubMed  CAS  Google Scholar 

  12. Battaglino R, Fu J, Spate U, et al. Serotonin regulates osteoclast differentiation through its transporter. J Bone Miner Res. 2004;19:1420–31.

    Article  PubMed  CAS  Google Scholar 

  13. Gustafsson BI, Thommesen L, Stunes AK, et al. Serotonin and fluoxetine modulate bone cell function in vitro. J Cell Biochem. 2006;98:139–51.

    Article  PubMed  CAS  Google Scholar 

  14. Michelson D, Stratakis C, Hill L, et al. Bone mineral density in women with depression. N Engl J Med. 1996;335:1176–81.

    Article  PubMed  CAS  Google Scholar 

  15. 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;61:488–94.

    PubMed  Google Scholar 

  16. Diem SJ, Blackwell TL, Stone KL, et al. Depressive symptoms and rates of bone loss at the hip in older women. J Am Geriatr Soc. 2007;55:824–31.

    Article  PubMed  Google Scholar 

  17. 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;159:484–90.

    Article  PubMed  CAS  Google Scholar 

  18. Sogaard AJ, Joakimsen RM, Tverdal A, Fonnebo V, Magnus JH, Berntsen GK. Long-term mental distress, bone mineral density and non-vertebral fractures. The Tromso Study. Osteoporos Int. 2005;16:887–97.

    Article  PubMed  CAS  Google Scholar 

  19. 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;53:343–7.

    Article  PubMed  CAS  Google Scholar 

  20. Mussolino ME. Depression and hip fracture risk: the NHANES I epidemiologic follow-up study. Public Health Rep. 2005;120:71–5.

    PubMed  Google Scholar 

  21. Langer RD, White E, Lewis CE, Kotchen JM, Hendrix SL, Trevisan M. The Women’s Health Initiative Observational Study: baseline characteristics of participants and reliability of baseline measures. Ann Epidemiol. 2003;13:S107–21.

    Article  PubMed  Google Scholar 

  22. LaCroix AZ, Cauley JA, Pettinger M, et al. Statin use, clinical fracture, and bone density in postmenopausal women: results from the Women’s Health Initiative Observational Study. Ann Intern Med. 2003;139:97–104.

    PubMed  CAS  Google Scholar 

  23. WHI Study Group. Design of the Women’s Health Initiative clinical trial and observational study. Control Clin Trials. 1998;19:61–109.

    Article  Google Scholar 

  24. Hays J, Hunt JR, Hubbell FA, et al. The Women’s Health Initiative recruitment methods and results. Ann Epidemiol. 2003;13:S18–77.

    Article  PubMed  Google Scholar 

  25. Curb JD, McTiernan A, Heckbert SR, et al. Outcomes ascertainment and adjudication methods in the Women’s Health Initiative. Ann Epidemiol. 2003;13:S122–8.

    Article  PubMed  Google Scholar 

  26. Anderson GL, Manson J, Wallace R, et al. Implementation of the Women’s Health Initiative study design. Ann Epidemiol. 2003;13:S5–17.

    Article  PubMed  Google Scholar 

  27. Burnam MA, Wells KB, Leake B, Landsverk J. Development of a brief screening instrument for detecting depressive disorders. Med Care. 1988;26:775–89.

    Article  PubMed  CAS  Google Scholar 

  28. Tuunainen A, Langer RD, Klauber MR, Kripke DF. Short version of the CES-D (Burnam screen) for depression in reference to the structured psychiatric interview. Psychiatry Res. 2001;103:261–70.

    Article  PubMed  CAS  Google Scholar 

  29. WHI Clinical Coordinating Center. WHI Scientific Resources website: Data Collection Procedures. Available at: http://www.whiscience.org/about/collection.php. Accessed January 18, 2008.

  30. DXA Quality Assurance. Available at: www.nhlbi.nih.gov/resources/deca/whios/studydoc/procedur/bone/1.pdf. Accessed January 18, 2008.

  31. Chen Z, Kooperberg C, Pettinger MB, et al. Validity of self-report for fractures among a multiethnic cohort of postmenopausal women: results from the Women’s Health Initiative observational study and clinical trials. Menopause. 2004;11:264–74.

    Article  PubMed  Google Scholar 

  32. Bauer DC, Browner WS, Cauley JA, et al. Factors associated with appendicular bone mass in older women. The Study of Osteoporotic Fractures Research Group. Ann Intern Med. 1993;118:657–65.

    PubMed  CAS  Google Scholar 

  33. Greenland S, Rothman KJ. Modern Epidemiology. 2nd ed. Philadelphia, PA: Lippincott-Raven; 1998.

    Google Scholar 

  34. Ensrud KE, Blackwell TL, Mangione CM, et al. Central nervous system-active medications and risk for falls in older women. J Am Geriatr Soc. 2002;50:1629–37.

    Article  PubMed  Google Scholar 

  35. Yazici KM, Akinci A, Sutcu A, Ozcakar L. Bone mineral density in premenopausal women with major depressive disorder. Psychiatry Res. 2003;117:271–5.

    Article  PubMed  Google Scholar 

  36. Furlan PM, Ten Have T, Cary M, et al. The role of stress-induced cortisol in the relationship between depression and decreased bone mineral density. Biol Psychiatry. 2005;57:911–7.

    Article  PubMed  CAS  Google Scholar 

  37. Mussolino ME, Jonas BS, Looker AC. Depression and bone mineral density in young adults: results from NHANES III. Psychosom Med. 2004;66:533–7.

    Article  PubMed  Google Scholar 

  38. Diem SJ, Blackwell TL, Stone KL, et al. Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med. 2007;167:1240–5.

    Article  PubMed  Google Scholar 

  39. Ensrud KE, Blackwell T, Mangione CM, et al. Central nervous system active medications and risk for fractures in older women. Arch Intern Med. 2003;163:949–57.

    Article  PubMed  Google Scholar 

  40. Richards JB, Papaioannou A, Adachi JD, et al. Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med. 2007;167:188–94.

    Article  PubMed  CAS  Google Scholar 

  41. Vestergaard P, Rejnmark L, Mosekilde L. Anxiolytics, sedatives, antidepressants, neuroleptics and the risk of fracture. Osteoporos Int. 2006;17:807–16.

    Article  PubMed  CAS  Google Scholar 

  42. French DD, Campbell R, Spehar A, Cunningham F, Foulis P. Outpatient medications and hip fractures in the US: a national veterans study. Drugs Aging. 2005;22:877–85.

    Article  PubMed  Google Scholar 

  43. Liu B, Anderson G, Mittmann N, To T, Axcell T, Shear N. Use of selective serotonin-reuptake inhibitors of tricyclic antidepressants and risk of hip fractures in elderly people. Lancet. 1998;351:1303–7.

    Article  PubMed  CAS  Google Scholar 

  44. Hubbard R, Farrington P, Smith C, Smeeth L, Tattersfield A. Exposure to tricyclic and selective serotonin reuptake inhibitor antidepressants and the risk of hip fracture. Am J Epidemiol. 2003;158:77–84.

    Article  PubMed  Google Scholar 

  45. Ray WA, Griffin MR, Schaffner W, Baugh DK, Melton LJ 3rd. Psychotropic drug use and the risk of hip fracture. N Engl J Med. 1987;316:363–9.

    Article  PubMed  CAS  Google Scholar 

  46. Ray WA, Griffin M, Malcolm E. Cyclic antidepressants and the risk of hip fracture. Arch Intern Med. 1991;151:754–6.

    Article  PubMed  CAS  Google Scholar 

  47. Schneeweiss S, Wang PS. Association between SSRI use and hip fractures and the effect of residual confounding bias in claims database studies. J Clin Psychopharmacol. 2004;24:632–8.

    Article  PubMed  Google Scholar 

  48. Fink HA, Milavetz DL, Palermo L, et al. What proportion of incident radiographic vertebral deformities is clinically diagnosed and vice versa? J Bone Miner Res. 2005;20:1216–22.

    Article  PubMed  Google Scholar 

  49. Majumdar SR, Kim N, Colman I, et al. Incidental vertebral fractures discovered with chest radiography in the emergency department: prevalence, recognition, and osteoporosis management in a cohort of elderly patients. Arch Intern Med. 2005;165:905–9.

    Article  PubMed  Google Scholar 

  50. Johnson J, Weissman MM, Klerman GL. Service utilization and social morbidity associated with depressive symptoms in the community. JAMA. 1992;267:1478–83.

    Article  PubMed  CAS  Google Scholar 

  51. Simon G, Ormel J, VonKorff M, Barlow W. Health care costs associated with depressive and anxiety disorders in primary care. Am J Psychiatry. 1995;152:352–7.

    PubMed  CAS  Google Scholar 

  52. Hansen MS, Fink P, Frydenberg M, Oxhoj ML. Use of health services, mental illness, and self-rated disability and health in medical inpatients. Psychosom Med. 2002;64:668–75.

    Article  PubMed  Google Scholar 

  53. Duddu V, Isaac MK, Chaturvedi SK. Somatization, somatosensory amplification, attribution styles and illness behaviour: a review. Int Rev Psychiatry. 2006;18:25–33.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors thank Dr. Susan Ott, Department of Medicine University of Washington, for her review and suggestions on the manuscript.

Funding

The WHI program is funded by the National Heart, Lung, and Blood Institute, U.S. Department of Health and Human Services. In addition, this analysis was funded in part from a Group Health Community Foundation grant.

WHI Investigators

Program Office: (National Heart, Lung, and Blood Institute, Bethesda, Maryland) Elizabeth Nabel, Jacques Rossouw, Shari Ludlam, Linda Pottern, Joan McGowan, Leslie Ford, and Nancy Geller.

Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA)

Ross Prentice, Garnet Anderson, Andrea LaCroix, Charles L. Kooperberg, Ruth E. Patterson, Anne McTiernan; (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker; (Medical Research Labs, Highland Heights, KY) Evan Stein; (University of California at San Francisco, San Francisco, CA) Steven Cummings.

Clinical Centers: (Albert Einstein College of Medicine, Bronx, NY) Sylvia Wassertheil-Smoller; (Baylor College of Medicine, Houston, TX) Jennifer Hays; (Brigham and Women’s Hospital, Harvard Medical School, Boston, MA) JoAnn Manson; (Brown University, Providence, RI) Annlouise R. Assaf; (Emory University, Atlanta, GA) Lawrence Phillips; (Fred Hutchinson Cancer Research Center, Seattle, WA) Shirley Beresford; (George Washington University Medical Center, Washington, DC) Judith Hsia; (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA) Rowan Chlebowski; (Kaiser Permanente Center for Health Research, Portland, OR) Evelyn Whitlock; (Kaiser Permanente Division of Research, Oakland, CA) Bette Caan; (Medical College of Wisconsin, Milwaukee, WI) Jane Morley Kotchen; (MedStar Research Institute/Howard University, Washington, DC) Barbara V. Howard; (Northwestern University, Chicago/Evanston, IL) Linda Van Horn; (Rush Medical Center, Chicago, IL) Henry Black; (Stanford Prevention Research Center, Stanford, CA) Marcia L. Stefanick; (State University of New York at Stony Brook, Stony Brook, NY) Dorothy Lane; (The Ohio State University, Columbus, OH) Rebecca Jackson; (University of Alabama at Birmingham, Birmingham, AL) Cora E. Lewis; (University of Arizona, Tucson/Phoenix, AZ) Tamsen Bassford; (University at Buffalo, Buffalo, NY) Jean Wactawski-Wende; (University of California at Davis, Sacramento, CA) John Robbins; (University of California at Irvine, CA) F. Allan Hubbell; (University of California at Los Angeles, Los Angeles, CA) Howard Judd; (University of California at San Diego, LaJolla/Chula Vista, CA) Robert D. Langer; (University of Cincinnati, Cincinnati, OH) Margery Gass; (University of Florida, Gainesville/Jacksonville, FL) Marian Limacher; (University of Hawaii, Honolulu, HI) David Curb; (University of Iowa, Iowa City/Davenport, IA) Robert Wallace; (University of Massachusetts/Fallon Clinic, Worcester, MA) Judith Ockene; (University of Medicine and Dentistry of New Jersey, Newark, NJ) Norman Lasser; (University of Miami, Miami, FL) Mary Jo O’Sullivan; (University of Minnesota, Minneapolis, MN) Karen Margolis; (University of Nevada, Reno, NV) Robert Brunner; (University of North Carolina, Chapel Hill, NC) Gerardo Heiss; (University of Pittsburgh, Pittsburgh, PA) Lewis Kuller; (University of Tennessee, Memphis, TN) Karen C. Johnson; (University of Texas Health Science Center, San Antonio, TX) Robert Brzyski; (University of Wisconsin, Madison, WI) Gloria E. Sarto; (Wake Forest University School of Medicine, Winston-Salem, NC) Denise Bonds; (Wayne State University School of Medicine/Hutzel Hospital, Detroit, MI) Susan Hendrix.

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Correspondence to Leslie Spangler VMD, PhD.

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Spangler, L., Scholes, D., Brunner, R.L. et al. Depressive Symptoms, Bone Loss, and Fractures in Postmenopausal Women. J GEN INTERN MED 23, 567–574 (2008). https://doi.org/10.1007/s11606-008-0525-0

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