Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Drugs & Aging
Published in: Drugs & Aging 1/2016

01-01-2016 | Review Article

Effects of Depression and Serotonergic Antidepressants on Bone: Mechanisms and Implications for the Treatment of Depression

Authors: Brisa S. Fernandes, Jason M. Hodge, Julie A. Pasco, Michael Berk, Lana J. Williams

Published in: Drugs & Aging | Issue 1/2016

Login to get access

Abstract

Osteoporosis is a chronic skeletal disease marked by microarchitectural deterioration of the bone matrix and depletion of bone mineral density (BMD), with a consequent increased risk for fragility fractures. It has been frequently associated with depression, which is also a chronic and debilitating disorder with high prevalence. Selective serotonin reuptake inhibitors (SSRIs), first-line agents in the pharmacological treatment of mood and anxiety disorders, have also been shown to negatively affect bone metabolism. SSRIs are the most prescribed antidepressants worldwide and a large number of persons at risk of developing osteoporosis, including older patients, will receive these antidepressants. Therefore, a proper musculoskeletal evaluation of individuals who are being targeted for or using SSRIs is a priority. The aim of this article is to review the evidence regarding the effects of depression and serotonergic antidepressants on bone and its implications for clinical care.
Literature
1.
Consensus development conference: prophylaxis and treatment of osteoporosis. Am J Med. 1991;90:107–10
2.
Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002;359(9319):1761–7.PubMedCrossRef
3.
Pasco JA, Sanders KM, Hoekstra FM, Henry MJ, Nicholson GC, Kotowicz MA. The human cost of fracture. Osteoporos Int. 2005;16(12):2046–52.PubMedCrossRef
4.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed (DSM-5). Washington, DC: American Psychiatric Association; 2013.
5.
Aloumanis K, Mavroudis K. The, “depressive” face of osteoporosis and the “osteoporotic” face of depression. Hormones (Athens). 2013;12(3):350–62.PubMed
6.
Williams LJ, Berk M, Henry MJ, Stuart AL, Brennan SL, Jacka FN, et al. Depression following fracture in women: a study of age-matched cohorts. BMJ Open. 2014;4(2):e004226.PubMedPubMedCentralCrossRef
7.
8.
Williams LJ, Pasco JA, Jacka FN, Henry MJ, Dodd S, Berk M. Depression and bone metabolism. A review. Psychother Psychosom. 2009;78(1):16–25.PubMedCrossRef
9.
Yirmiya R, Bab I. Major depression is a risk factor for low bone mineral density: a meta-analysis. Biol Psychiatry. 2009;66(5):423–32.PubMedCrossRef
10.
Bab I, Yirmiya R. Depression, selective serotonin reuptake inhibitors, and osteoporosis. Curr Osteoporos Rep. 2010;8(4):185–91.PubMedCrossRef
11.
Gebara MA, Shea ML, Lipsey KL, Teitelbaum SL, Civitelli R, Muller DJ, et al. Depression, antidepressants, and bone health in older adults: a systematic review. J Am Geriatr Soc. 2014;62(8):1434–41.PubMedPubMedCentralCrossRef
12.
Pirraglia PA, Stafford RS, Singer DE. Trends in prescribing of selective serotonin reuptake inhibitors and other newer antidepressant agents in adult primary care. Prim Care Companion J Clin Psychiatry. 2003;5(4):153–7.PubMedPubMedCentralCrossRef
13.
Vaswani M, Linda FK, Ramesh S. Role of selective serotonin reuptake inhibitors in psychiatric disorders: a comprehensive review. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27(1):85–102.PubMedCrossRef
14.
15.
Hodge JM, Wang Y, Berk M, Collier FM, Fernandes TJ, Constable MJ, et al. Selective serotonin reuptake inhibitors inhibit human osteoclast and osteoblast formation and function. Biol Psychiatry. 2013;74(1):32–9.PubMedCrossRef
16.
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(6):732–6.PubMedCrossRef
17.
Williams LJ, Bjerkeset O, Langhammer A, Berk M, Pasco JA, Henry MJ, et al. The association between depressive and anxiety symptoms and bone mineral density in the general population: the HUNT study. J Affect Disord. 2011;131(1–3):164–71.PubMedCrossRef
18.
Eskandari F, Martinez PE, Torvik S, Phillips TM, Sternberg EM, Mistry S, et al. Low bone mass in premenopausal women with depression. Arch Intern Med. 2007;167(21):2329–36.PubMedCrossRef
19.
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(8):1309–20.PubMedCrossRef
20.
Williams LJ, Pasco JA, Jacka FN, Hodge JM, Kotowicz MA, Berk M. Quantitative Heel Ultrasound (QUS) measures of bone quality in association with mood and anxiety disorders. J Affect Disord. 2013;146(3):395–400.PubMedCrossRef
21.
Haney EM, Warden SJ, Bliziotes MM. Effects of selective serotonin reuptake inhibitors on bone health in adults: time for recommendations about screening, prevention and management? Bone. 2010;46(1):13–7.PubMedPubMedCentralCrossRef
22.
Chen F, Hahn TJ, Weintraub NT. Do SSRIs play a role in decreasing bone mineral density? J Am Med Dir Assoc. 2012;13(5):413–7.PubMedCrossRef
23.
Tsapakis EM, Gamie Z, Tran GT, Adshead S, Lampard A, Mantalaris A, et al. The adverse skeletal effects of selective serotonin reuptake inhibitors. Eur Psychiatry. 2012;27(3):156–69.PubMedCrossRef
24.
Wu Q, Bencaz AF, Hentz JG, Crowell MD. Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case-control studies. Osteoporos Int. 2012;23(1):365–75.PubMedCrossRef
25.
Wu Q, Qu W, Crowell MD, Hentz JG, Frey KA. Tricyclic antidepressant use and risk of fractures: a meta-analysis of cohort and case-control studies. J Bone Miner Res. 2013;28(4):753–63.PubMedCrossRef
26.
Haney EM, Warden SJ. Skeletal effects of serotonin (5-hydroxytryptamine) transporter inhibition: evidence from clinical studies. J Musculoskelet Neuronal Interact. 2008;8(2):133–45.PubMed
27.
Rizzoli R, Cooper C, Reginster JY, Abrahamsen B, Adachi JD, Brandi ML, et al. Antidepressant medications and osteoporosis. Bone. 2012;51(3):606–13.PubMedCrossRef
28.
Eom CS, Lee HK, Ye S, Park SM, Cho KH. Use of selective serotonin reuptake inhibitors and risk of fracture: a systematic review and meta-analysis. J Bone Miner Res. 2012;27(5):1186–95.PubMedCrossRef
29.
Richards JB, Papaioannou A, Adachi JD, Joseph L, Whitson HE, Prior JC, et al. Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med. 2007;167(2):188–94.PubMedCrossRef
30.
Ziere G, Dieleman JP, van der Cammen TJ, Hofman A, Pols HA, Stricker BH. Selective serotonin reuptake inhibiting antidepressants are associated with an increased risk of nonvertebral fractures. J Clin Psychopharmacol. 2008;28(4):411–7.PubMedCrossRef
31.
Williams L, Pasco JA, Stuart AL, Jacka FN, Brennan SL, Dobbins AG, et al. Psychiatric disorders, psychotropic medication use and falls among women: an observational study. BMC Psychiatry. 2015;15:75.PubMedPubMedCentralCrossRef
32.
Vestergaard P, Rejnmark L, Mosekilde L. Anxiolytics, sedatives, antidepressants, neuroleptics and the risk of fracture. Osteoporos Int. 2006;17(6):807–16.PubMedCrossRef
33.
Diem SJ, Blackwell TL, Stone KL, Yaffe K, Haney EM, Bliziotes MM, et al. Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med. 2007;167(12):1240–5.PubMedCrossRef
34.
35.
Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schutz G, et al. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell. 2008;135(5):825–37.PubMedPubMedCentralCrossRef
36.
Yadav VK, Oury F, Suda N, Liu ZW, Gao XB, Confavreux C, et al. A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell. 2009;138(5):976–89.PubMedPubMedCentralCrossRef
37.
38.
Chabbi-Achengli Y, Coudert AE, Callebert J, Geoffroy V, Cote F, Collet C, et al. Decreased osteoclastogenesis in serotonin-deficient mice. Proc Natl Acad Sci USA. 2012;109(7):2567–72.PubMedPubMedCentralCrossRef
39.
40.
Cui Y, Niziolek PJ, MacDonald BT, Zylstra CR, Alenina N, Robinson DR, et al. Lrp5 functions in bone to regulate bone mass. Nat Med. 2011;17(6):684–91.PubMedPubMedCentralCrossRef
41.
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(5):477–86.PubMedCrossRef
42.
Westbroek I, van der Plas A, de Rooij KE, Klein-Nulend J, Nijweide PJ. Expression of serotonin receptors in bone. J Biol Chem. 2001;276(31):28961–8.PubMedCrossRef
43.
Collet C, Schiltz C, Geoffroy V, Maroteaux L, Launay JM, de Vernejoul MC. The serotonin 5-HT2B receptor controls bone mass via osteoblast recruitment and proliferation. FASEB J. 2008;22(2):418–27.PubMedCrossRef
44.
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(1–2):1–9.PubMedCrossRef
45.
Warden SJ, Haney EM. Skeletal effects of serotonin (5-hydroxytryptamine) transporter inhibition: evidence from in vitro and animal-based studies. J Musculoskelet Neuronal Interact. 2008;8(2):121–32.PubMedPubMedCentral
46.
Warden SJ, Hassett SM, Bond JL, Rydberg J, Grogg JD, Hilles EL, et al. Psychotropic drugs have contrasting skeletal effects that are independent of their effects on physical activity levels. Bone. 2010;46(4):985–92.PubMedPubMedCentralCrossRef
47.
Brommage R, Liu J, Doree D, Yu W, Powell DR, Yang QM. Adult Tph2 knockout mice without brain serotonin have moderately elevated spine trabecular bone but moderately low cortical bone thickness. Bonekey Rep. 2015;4:718.PubMedCrossRef
Metadata
Title
Effects of Depression and Serotonergic Antidepressants on Bone: Mechanisms and Implications for the Treatment of Depression
Authors
Brisa S. Fernandes
Jason M. Hodge
Julie A. Pasco
Michael Berk
Lana J. Williams
Publication date
01-01-2016
Publisher
Springer International Publishing
Published in
Drugs & Aging / Issue 1/2016
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI
https://doi.org/10.1007/s40266-015-0323-4

Other articles of this Issue 1/2016

Drugs & Aging 1/2016 Go to the issue

Therapy in Practice

Pain Relief for an Osteoarthritic Knee in the Elderly: A Practical Guide

Review Article

Clinical Presentation, Diagnosis and Treatment of Attention-Deficit Hyperactivity Disorder (ADHD) in Older Adults: A Review of the Evidence and its Implications for Clinical Care

Original Research Article

Prevalence and Risk Factors Associated with Use of QT-Prolonging Drugs in Hospitalized Older People

Short Communication

Polypharmacy and Renal Failure in Nursing Home Residents: Results of the Inappropriate Medication in Patients with Renal Insufficiency in Nursing Homes (IMREN) Study

Leading Article

OnabotulinumtoxinA Treatment for Overactive Bladder in the Elderly: Practical Points and Future Prospects

Original Research Article

Prevention of Adverse Drug Reactions in Hospitalised Older Patients Using a Software-Supported Structured Pharmacist Intervention: A Cluster Randomised Controlled Trial
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits