Highlights
- •Depression has been associated with increased risk of fractures.
- •This longitudinal study confirmed that exposure to depression increases the risk of fractures, but the effect of this association is modest.
- •In this older cohort with multiple competing risks for fractures, exposure to antidepressant medications (including SSRIs) did not increase fracture risk.
- •The management of older adults with depression should include strategies for fracture prevention.
Abstract
Introduction
Fractures are common and disabling health events, particularly later in life. The
presence of clinically significant depressive symptoms has been associated with increased
risk of fractures, and we designed the present study to clarify if this association
is likely to be causal or due to the confounding effect of measures associated with
both fractures and depression.
Method
Cohort study of a community-derived sample of 4224 men aged 70 to 88 years at the
start of the follow-up period of up to 17 years. Clinically significant symptoms of
depression were defined as a recorded diagnosis of depressive episode in the Western
Australian Data Linkage System (WADLS) or by a total score of 7 or greater on the
15-item Geriatric Depression Scale. Health contacts associated with fractures were
retrieved from WADLS. Other measures included age, past history of fractures, education,
smoking, frailty, poor vision, falls, medications, and the concentration of vitamin
D, homocysteine, hsCRP and testosterone. Death was considered a competing risk for
fractures.
Results
911 (21.6%) participants had a bone fracture during follow-up. After adjustment for
multiple potential confounders, past and current depression were associated with an
increase in the risk of novel fractures; respective odds ratios were 1.41 (95%CI =
1.03, 1.93) and 1.64 (95%CI = 1.20, 2.25). Parsimonious competing risk regression
showed that both past and current depression were associated with an increase in the
risk of novel fractures: sub-hazard ratio = 1.29 (95%CI = 1.03, 1.63) and 1.27 (95%CI
= 1.05, 1.55) respectively. Estimation of confounding due to unmeasured factors showed
that a small additional effect could potentially dilute the association between depression
and fractures.
Discussion
History of clinically significant symptoms of depression is associated with an increased
risk of future fractures. This association may be due to multiple other associated
risk factors, both measured and unmeasured, but nevertheless the presence of depression
should alert clinicians to the need to develop a management plan that includes the
management not only of depression but also of fracture risk.
Keywords
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References
- Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.Lancet. 2016; 388: 1603-1658
- Patients with depression are less likely to follow recommendations to reduce cardiac risk during recovery from a myocardial infarction.Arch Intern Med. 2000; 160: 1818-1823
- Falls, depression and antidepressants in later life: a large primary care appraisal.PLoS One. 2008; 3: e2423
- Depression and risk of fracture and bone loss: an updated meta-analysis of prospective studies.Osteoporos Int. 2018; 29: 1303-1312
- Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case-control studies.Osteoporos Int. 2012; 23: 365-375
- Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial.Lancet Neurol. 2020; 19: 651-660
- Depression and smoking amongst older general practice patients.J Affect Disord. 2005; 86: 317-321
- 150 minutes of vigorous physical activity per week predicts survival and successful ageing: a population-based 11-year longitudinal study of 12 201 older Australian men.British journal of sports medicine. 2014; 48: 220-225
- A practical approach to assess depression risk and to guide risk reduction strategies in later life.Int Psychogeriatr. 2011; 23: 280-291
- Cigarette smoking, alcohol consumption, and risk of hip fracture in women.Arch Intern Med. 2001; 161: 983-988
- Physical activity and osteoporotic hip fracture risk in men.Arch Intern Med. 2000; 160: 705-708
- Low free testosterone concentration as a potentially treatable cause of depressive symptoms in older men.Arch Gen Psychiatry. 2008; 65: 283-289
- Vitamin D deficiency and depression in adults: systematic review and meta-analysis.Br J Psychiatry. 2013; 202: 100-107
- U-Shaped Association of Plasma Testosterone, and no Association of Plasma Estradiol, with Incidence of Fractures in Men.J Clin Endocrinol Metab. 2020; 105
- Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation.Osteoporos Int. 2016; 27: 367-376
- Homocysteine levels and the risk of osteoporotic fracture.N Engl J Med. 2004; 350: 2033-2041
- Benzodiazepines, Z-drugs and the risk of hip fracture: A systematic review and meta-analysis.PLoS One. 2017; 12e0174730
- Cohort Profile: The Health In Men Study (HIMS).Int J Epidemiol. 2009; 38: 48-52
- Mortality among People with Severe Mental Disorders Who Reach Old Age: A Longitudinal Study of a Community-Representative Sample of 37892 Men.PLoS One. 2014; 9e111882
- How many older people are frail? Using multiple imputation to investigate frailty in the population.J Am Med Dir Assoc. 2015; 16: e431-e437
- Population-based linkage of health records in Western Australia: development of a health services research linked database.Aust N Z J Public Health. 1999; 23: 453-459
- A decade of data linkage in Western Australia: strategic design, applications and benefits of the WA data linkage system.Aust Health Rev. 2008; 32: 766-777
- Short versions of the geriatric depression scale: a study of their validity for the diagnosis of a major depressive episode according to ICD-10 and DSM-IV.Int J Geriatr Psychiatry. 1999; 14: 858-865
- Low free testosterone predicts frailty in older men: the health in men study.J Clin Endocrinol Metab. 2010; 95: 3165-3172
- Polymorphisms of the CRP gene inhibit inflammatory response and increase susceptibility to depression: the Health in Men Study.Int J Epidemiol. 2009; 38: 1049-1059
- Vitamin D concentration and its association with past, current and future depression in older men: The Health In Men Study.Maturitas. 2015; 81: 36-41
- Homocysteine and depression in later life.Arch Gen Psychiatry. 2008; 65: 1286-1294
- Prospective longitudinal study of testosterone and incident depression in older men: The Health In Men Study.Psychoneuroendocrinology. 2015; 64: 57-65
- Sensitivity Analysis in Observational Research: Introducing the E-Value.Ann Intern Med. 2017; 167: 268-274
- A. note on the magnitude of hazard ratios.Cancer. 2016; 122: 1298-1299
- 3412.0 - Migration, Australia, 2013-2014.Australian Bureau of Statistics, Canberra: Australia2015
- Low bone mass in premenopausal women with depression.Arch Intern Med. 2007; 167: 2329-2336
- Effects of Depression and Serotonergic Antidepressants on Bone: Mechanisms and Implications for the Treatment of Depression.Drugs Aging. 2016; 33: 21-25
- Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial.Lancet. 2019; 393: 265-274
- Association Between Antidepressant Drug Use and Hip Fracture in Older People Before and After Treatment Initiation.JAMA Psychiatry. 2019; 76: 172-179
Article info
Publication history
Published online: December 21, 2020
Accepted:
December 15,
2020
Received in revised form:
October 16,
2020
Received:
June 12,
2020
Identification
Copyright
© 2020 Elsevier B.V. All rights reserved.