Calcified Tissue International

, Volume 103, Issue 2, pp 125–130 | Cite as

Selective Serotonin Reuptake Inhibitors (SSRIs) and Markers of Bone Turnover in Men

  • Lana J. Williams
  • Michael Berk
  • Jason M. Hodge
  • Mark A. Kotowicz
  • Amanda L. Stuart
  • Vinoomika Chandrasekaran
  • Jasmine Cleminson
  • Julie A. Pasco
Original Research


Selective serotonin reuptake inhibitors (SSRIs) have been shown to have a clinically significant impact on bone metabolism. To explore this further, we aimed to determine whether these agents are associated with serum markers of bone turnover utilising a population-based sample of men (n = 1138; 20–96 year) participating in the Geelong Osteoporosis Study. Blood samples were obtained and the bone resorption marker, C-telopeptide (CTx) and formation marker, type 1 procollagen amino-terminal-propeptide (PINP) were measured. Anthropometry and socio-economic status (SES) were determined and information on medication use and lifestyle was obtained via questionnaire. Lifetime mood disorders were assessed using semi-structured clinical interviews. Thirty-seven (3.3%) men reported using SSRIs. Age was an effect modifier in the association between SSRIs and markers of bone turnover. Among younger men (20–60 year; n = 557), adjusted mean CTx and PINP values were 12.4% [16.7 (95% CI 14.6–18.8) vs 19.1 (95% CI 18.7–19.4) pg/ml, p = 0.03] and 13.6% [5.6 (95% CI 4.9–6.3) vs 6.4 (95% CI 6.3–6.6) pg/ml, p = 0.02] lower among SSRI users compared to non-users, respectively. No differences in SSRI use and markers of bone turnover were detected among older men (61–94 year; all p > 0.05). These patterns persisted after further adjustment for activity, alcohol, smoking, SES, depression, bone active medications and other antidepressants. Our data suggest that SSRI use is associated with alterations in bone turnover markers among younger men. The observed decreases in both CTx and PINP are likely to contribute to a low bone turnover state and increased skeletal fragility with this potential imbalance between formation and resorption resulting in subsequent bone loss.


Antidepressants Bone turnover Bone metabolism Osteoporosis Depression Psychiatry 



This work was supported by the National Health and Medical Research Council (NHMRC), Australia (Projects 299831, 628582, 1009367, 1026265, 1021345, 1104438). LJW is supported by a NHMRC Career Development Fellowship (1064272). MB is supported by a NHMRC Senior Principal Research Fellowship (1059660). VC and JC are supported by Postgraduate Scholarships from Deakin University. The funding providers played no role in the design or conduct of the study; collection, management, analysis and interpretation of the data; or in preparation, review or approval of the manuscript.

Compliance with Ethical Standards

Conflict of interest

LJW has received grant/research support from Eli Lilly, Pfizer, The University of Melbourne, Deakin University. MB has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Rotary Health, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Meat and Livestock Board, Organon, Novartis, Mayne Pharma, Servier and Woolworths, has been a speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth, and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck Merck, Pfizer and Servier. JAP has recently received grant/research support from the National Health and Medical Research Council (NHMRC), BUPA Foundation, Amgen/GlaxoSmithKline/Osteoporosis Australia/Australian and New Zealand Bone and Mineral Society, Western Alliance, Barwon Health, Deakin University and the Geelong Community Foundation. JH, MAK, ALS, VC and JC have no disclosures.

Ethical Approval

The Human Research Ethics Committee at Barwon Health approved the study.

Human and Animal Rights and Informed Consent

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Pratt LA, Brody DJ, Gu Q (2011) Antidepressant use in persons aged 12 and over: United States, 2005–2008. NCHS Data Brief 76:1–8Google Scholar
  2. 2.
    Hendrickx G, Boudin E, Van Hul W (2015) A look behind the scenes: the risk and pathogenesis of primary osteoporosis. Nat Rev Rheumatol 11:462–74CrossRefPubMedGoogle Scholar
  3. 3.
    Henry M, Pasco J, Nicholson G, Kotowicz M (2011) Prevalence of osteoporosis in Australian men and women: Geelong Osteoporosis Study. Med J Aust 195:321–322CrossRefPubMedGoogle Scholar
  4. 4.
    Johnell O, Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17:1726–1733CrossRefPubMedGoogle Scholar
  5. 5.
    Watts JJ, Abimanyi-Ochom J, Sanders KM (2012) Osteoporosis costing all Australians a new burden of disease analysis—2012 to 2022 report. Osteoprosis Australia, Glebe, NSWGoogle Scholar
  6. 6.
    Rabenda V, Nicolet D, Beaudart C, Bruyere O, Reginster JY (2013) Relationship between use of antidepressants and risk of fractures: a meta-analysis. Osteoporos Int 24:121–137CrossRefPubMedGoogle Scholar
  7. 7.
    Wu Q, Bencaz AF, Hentz JG, Crowell MD (2012) Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case-control studies. Osteoporos Int 23:365–375CrossRefPubMedGoogle Scholar
  8. 8.
    Fernandes BS, Hodge JM, Pasco JA, Berk M, Williams LJ (2016) Effects of depression and serotonergic antidepressants on bone: mechanisms and implications for the treatment of depression. Drugs Aging 33:21–25CrossRefPubMedGoogle Scholar
  9. 9.
    Williams LJ, Pasco JA, Jacka FN, Henry MJ, Dodd S, Berk M (2009) Depression and bone metabolism. Rev Psychother Psychosom 78:16–25CrossRefGoogle Scholar
  10. 10.
    Williams LJ, Pasco JA, Stuart AL, Jacka FN, Brennan SL, Dobbins AG, Honkanen RJ, Koivumaa-Honkanen H, Rauma PH, Berk M (2015) Psychiatric disorders, psychotropic medication use and falls among women: an observational study. BMC Psychiatry 15:75CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Stuart AL, Pasco JA, Jacka FN, Berk M, Williams LJ (2018) Falls and depression in men: a population-based study. Am J Mens Health 12:14–18CrossRefPubMedGoogle Scholar
  12. 12.
    World Health Organisation (2007) Prevention and management of osteoporosis: report of a WHO scientific group. In: World Health Organisation Scientific Group on the prevention and management of osteoporosis, GenevaGoogle Scholar
  13. 13.
    Pasco JA, Nicholson GC, Kotowicz MA (2012) Cohort profile: Geelong Osteoporosis Study. Int J Epidemiol 41:1565–1575CrossRefPubMedGoogle Scholar
  14. 14.
    First M, Spitzer R, Gibbon M, Williams J (2002) Structured clinical interview for DSM-IV-TR axis I disorders, research version, non-patient edition. (SCID-I/NP). Biometrics Research, New York State Psychiatric Institute, New YorkGoogle Scholar
  15. 15.
    Giles C, Ireland P (1996) Dietary questionnaire for epidemiological studies (version 2). The Cancer Council Victoria, MelbourneGoogle Scholar
  16. 16.
    Brennan SL, Henry MJ, Nicholson GC, Kotowicz MA, Pasco JA (2009) Socioeconomic status and risk factors for obesity and metabolic disorders in a population-based sample of adult females. Prev Med 49:165–171CrossRefPubMedGoogle Scholar
  17. 17.
    Brennan SL, Henry MJ, Nicholson GC, Kotowicz MA, Pasco JA (2010) Socioeconomic status, obesity and lifestyle in men: the Geelong Osteoporosis Study. J Mens Health 7:31–41CrossRefGoogle Scholar
  18. 18.
    Aydin H, Mutlu N, Akbas NB (2011) Treatment of a major depression episode suppresses markers of bone turnover in premenopausal women. J Psychiatr Res 45:1316–1320CrossRefPubMedGoogle Scholar
  19. 19.
    Shea ML, Garfield LD, Teitelbaum S, Civitelli R, Mulsant BH, Reynolds CF 3rd, Dixon D, Dore P, Lenze EJ (2013) Serotonin-norepinephrine reuptake inhibitor therapy in late-life depression is associated with increased marker of bone resorption. Osteoporos Int 24: 1741–1749CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Diem SJ, Joffe H, Larson JC, Tsai JN, Guthrie KA, LaCroix AZ, Ensrud KE, Freeman EW, Leder BZ (2014) Effects of escitalopram on markers of bone turnover: a randomized clinical trial. J Clin Endocrinol Metab 99:E1732-7CrossRefPubMedGoogle Scholar
  21. 21.
    Ortuno MJ, Robinson ST, Subramanyam P, Paone R, Huang YY, Guo XE, Colecraft HM, Mann JJ, Ducy P (2016) Serotonin-reuptake inhibitors act centrally to cause bone loss in mice by counteracting a local anti-resorptive effect. Nat Med 22:1170–1179CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Hodge JM, Wang Y, Berk M, Collier FM, Fernandes TJ, Constable MJ, Pasco JA, Dodd S, Nicholson GC, Kennedy RL, Williams LJ (2013) Selective serotonin reuptake inhibitors inhibit human osteoclast and osteoblast formation and function. Biol Psychiatry 74:32–39CrossRefPubMedGoogle Scholar
  23. 23.
    Fratzl-Zelman N, Roschger P, Misof BM, Nawrot-Wawrzyniak K, Potter-Lang S, Muschitz C, Resch H, Klaushofer K, Zwettler E (2011) Fragility fractures in men with idiopathic osteoporosis are associated with undermineralization of the bone matrix without evidence of increased bone turnover. Calcif Tissue Int 88:378–387CrossRefPubMedGoogle Scholar
  24. 24.
    Nguyen TV, Meier C, Center JR, Eisman JA, Seibel MJ (2007) Bone turnover in elderly men: relationships to change in bone mineral density. BMC Musculoskelet Disord 8:13CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Lockhart P, Guthrie B (2011) Trends in primary care antidepressant prescribing 1995–2007: a longitudinal population database analysis. Br J Gen Pract 61:e565–e572CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Lana J. Williams
    • 1
    • 2
  • Michael Berk
    • 1
    • 2
    • 3
    • 4
    • 5
  • Jason M. Hodge
    • 1
    • 2
    • 6
  • Mark A. Kotowicz
    • 1
    • 2
    • 7
  • Amanda L. Stuart
    • 1
  • Vinoomika Chandrasekaran
    • 1
  • Jasmine Cleminson
    • 1
  • Julie A. Pasco
    • 1
    • 2
    • 7
  1. 1.Deakin UniversityGeelongAustralia
  2. 2.Barwon HealthGeelongAustralia
  3. 3.Department of PsychiatryThe University of MelbourneParkvilleAustralia
  4. 4.Florey Institute of Neuroscience and Mental HealthParkvilleAustralia
  5. 5.Orygen the National Centre of Excellence in Youth Mental HealthParkvilleAustralia
  6. 6.Geelong Centre for Emerging Infectious DiseasesGeelongAustralia
  7. 7.Melbourne Medical School-Western PrecinctThe University of MelbourneSt AlbansAustralia

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