Hip Fracture Risk Among Older People Using Antidepressants

In This Article

Abstract and Introduction

Abstract

Background: hip fractures are usually caused by a combination of reduced bone mineral density and falls; using antidepressant drugs may affect both of these.

Objective: we aimed to examine associations between exposure to antidepressant drugs and the risk of hip fracture among older people, and, provided associations found, to estimate the attributable risk of hip fracture.

Design: we conducted a nationwide prospective cohort study of the 906,422 people in Norway born before 1945.

Methods: information on all prescriptions of antidepressants dispensed in 2004–10 and all primary hip fractures in 2005–10 was obtained from the Norwegian Prescription Database, and the Norwegian Hip Fracture Registry, respectively. The incidence rates of hip fracture during the time people were exposed and unexposed to antidepressant drugs were compared by calculating the standardised incidence ratio (SIR).

Results: altogether 39,938 people (4.4%) experienced a primary hip fracture. The risk of hip fracture was increased for people exposed to any antidepressant [SIR = 1.7, 95% confidence interval (CI) 1.7–1.8]; tricyclic antidepressants (SIR = 1.4, 95% CI: 1.3–1.5); selective serotonin reuptake inhibitors (SSRIs) (SIR = 1.8, 95% CI: 1.7–1.8) and other antidepressants (SIR = 1.6, 95% CI: 1.5–1.7). The risk of hip fracture attributable to exposure to antidepressant drugs was 4.7%.

Conclusions: this study indicated an increased risk of hip fracture among people exposed to antidepressants, especially those with serotonergic properties such as SSRIs. This association needs to be explored further in clinical studies.

Introduction

The risk of hip fracture increases with age. The estimated lifetime risk is 25% for women and 7% for men.^[1] Hip fractures represent critical events, with great implications for morbidity and mortality.^[2] Most hip fractures result from a combination of reduced bone mineral density and a fall;^[3] using antidepressants may affect both of these.^[4,5]

Antidepressants are prescribed to 10–25% of women and 5–20% of men 60 years and older in Europe and the USA, mostly selective serotonin reuptake inhibitors (SSRIs).^[6–9] Clinical guidelines recommend SSRIs for depression because they have fewer sedative, anticholinergic and cardiovascular side effects than tricyclic antidepressants (TCAs). Observational studies indicate associations between the use of antidepressants and hip fracture, especially recently initiated drug treatment.^[9–11] Some studies suggest that SSRIs may be associated with a greater risk of hip fracture than TCAs,^[10,12] postulating a specific serotonergic effect on bone physiology.^[13]

We aimed to examine associations between exposure to antidepressant drugs and the risk of hip fracture among older people. If we found associations, we aimed to estimate the attributable risk of hip fracture.

Table 1. Number of people in Norway born before 1945 who purchased antidepressant drugs during 2005–10 and proportions by various antidepressant subgroups
Study population	Any antidepressant (%)	Antidepressant subgroups (% of people who purchased)
		Therapeutic subgroup			Serotonergic properties
		TCA	SSRI	Others	Low	High
All (n = 906,422)	153,301 (16.9)	29.2	62.1	39.6	14.1	92.2
Women (n = 506,568)	105,830 (20.9)	30.8	63.2	38.8	14.0	92.6
Men (n = 399,854)	47,471 (11.9)	25.8	57.7	41.5	14.4	91.1

The totals in each of the subgroups do not add up to 100%, because individuals may have purchased more than one antidepressant.
TCA (ATC N06AA): tricyclic antidepressants (clomipramine, trimipramine, amitriptyline, nortriptyline and doxepin).
SSRI (N06AB): selective serotonin reuptake inhibitors (fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine and escitalopram).
Others (N06AG, N06AX): moclobemide, mianserin, mirtazapine, bupropion, venlafaxine, reboxetine and duloxetine.
High or intermediate serotonergic properties: All SSRIs, TCAs (clomipramine and amitriptyline) and others (mianserin, mirtazapine, venlafaxine and duloxetine).
Low or no serotonergic properties: TCAs (nortriptyline, doxepin and trimipramine), moclobemide, bupropion and reboxetine.

Table 2. Number of hip fractures (n) and excess risk of hip fracture (SIR, 95% CI) in Norway's population born before 1945 exposed to antidepressant drugs in 2005–10, by birth cohort and sex
Hip fractures observed during exposed person-days	Birth cohort (years)
	All		1935–44		1925–34		1915–24		<1915
	n	SIR (95% CI)	n	SIR (95% CI)	n	SIR (95% CI)	n	SIR (95% CI)	n	SIR (95% CI)
All	4,465	1.7 (1.7–1.8)	756	2.6 (2.4–2.8)	1,814	1.9 (1.8–2.0)	1,774	1.4 (1.3–1.5)	121	1.2 (1.0–1.4)
Women	3,594	1.7 (1.6–1.7)	561	2.5 (2.3–2.7)	1,431	1.9 (1.8–2.0)	1,493	1.4 (1.3–1.5)	109	1.2 (1.0–1.4)
Men	871	1.9 (1.8–2.0)	195	2.9 (2.6–3.4)	383	2.2 (2.0–2.4)	281	1.4 (1.2–1.6)	12	1.0 (0.5–1.7)

SIR, standardised incidence ratio. CI, confidence interval.

Table 3. Observed number of hip fractures (n) and excess risk of hip fracture (SIR, 95% CI) in Norway's population born before 1945 exposed to various antidepressant drug subgroups in 2005–10 (Exposed person days, DDD)
	Any antidepressant		Antidepressant subgroups
			Therapeutic subgroup						Serotonergic properties
			TCA		SSRI		Others		Low		High
	n	SIR (95% CI)	n	SIR (95% CI)	n	SIR (95% CI)	n	SIR (95% CI)	n	SIR (95% CI)	n	SIR (95% CI)
All	4,465	1.7 (1.7–1.8)	364	1.4 (1.3–1.5)	3,272	1.8 (1.7–1.8)	1,119	1.6 (1.5–1.7)	147	1.2 (1.1–1.5)	4,345	1.7 (1.7–1.8)
Women	3,594	1.7 (1.6–1.7)	305	1.4 (1.3–1.6)	2,632	1.7 (1.7–1.8)	898	1.6 (1.5–1.7)	120	1.2 (1.0–1.5)	3,499	1.7 (1.6–1.8)
Men	871	1.9 (1.8–2.0)	59	1.4 (1.1–1.8)	640	2.1 (1.9–2.2)	221	1.6 (1.4–1.8)	27	1.3 (0.8–1.9)	846	1.9 (1.8–2.1)
Attributable risk (% of hip fractures during DDD exposure throughout the study period)
All		4.7		0.3		3.6		1.0		0.1		4.6

SIR, standardised incidence ratio. CI, confidence interval. DDD, defined daily dose.
TCA (ATC N06AA): tricyclic antidepressants (clomipramine, trimipramine, amitriptyline, nortriptyline and doxepin).
SSRI (N06AB): selective serotonin reuptake inhibitors (fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine and escitalopram).
Others (ATC N06AG, N06AX): moclobemide, mianserin, mirtazapine, bupropion, venlafaxine, reboxetine and duloxetine.
High or intermediate serotonergic properties: all SSRIs, TCAs (clomipramine and amitriptyline) and others (mianserin, mirtazapine, venlafaxine and duloxetine).
Low or no serotonergic properties: TCAs (nortriptyline, doxepin and trimipramine), moclobemide, bupropion and reboxetine.

My Alerts

Add to Email Alerts

Your Name is required.

Subject is required.

Please enter a Recipient Address and/or check the Send me a copy checkbox.

Your email has been sent.

is an Invalid Email Address.

Increased Risk of Hip Fracture Among Older People Using Antidepressant Drugs

Data From the Norwegian Prescription Database and the Norwegian Hip Fracture Registry

Abstract and Introduction

Abstract

Introduction

Increased Risk of Hip Fracture Among Older People Using Antidepressant Drugs

Data From the Norwegian Prescription Database and the Norwegian Hip Fracture Registry

Abstract and Introduction

Abstract

Introduction

Tables

Tables

Tables

References

Authors and Disclosures

Authors and Disclosures

Sidebar

Sidebar

Key Points

Email This

Feedback