Atopic eczema and fracture risk in adults: A population-based cohort study

Abstract

Background: Limited evidence suggests increased fracture risk in people with atopic eczema. Any link could have substantial effect; atopic eczema is common, and fractures have associated morbidity and mortality.

Objective: We sought to examine whether atopic eczema is associated with fracture and whether fracture risk varies with eczema severity.

Methods: We performed a matched cohort study set in primary care (Clinical Practice Research Datalink GOLD 1998-2016) and linked hospital admissions data (Hospital Episode Statistics), including adults (≥18 years old) with atopic eczema matched (by age, sex, general practice, and cohort entry date) with up to 5 individuals without eczema. We estimated hazard ratios (HRs) from stratified Cox regression comparing risk of major osteoporotic (hip, pelvis, spine, wrist, and proximal humerus) fractures individually and any fracture in those with and without atopic eczema.

Results: We identified 526,808 people with atopic eczema and 2,569,030 people without atopic eczema. Those with eczema had increased risk of hip (HR, 1.10; 99% CI, 1.06-1.14), pelvic (HR, 1.10; 99% CI, 1.02-1.19), spinal (HR, 1.18; 99% CI, 1.10-1.27), and wrist (HR, 1.07; 99% CI, 1.03,-1.11) fractures. We found no evidence of increased proximal humeral (HR, 1.06; 99% CI, 0.97-1.15) fracture risk. Fracture risk increased with increasing eczema severity, with the strongest associations in people with severe eczema (compared with those without) for spinal (HR, 2.09; 99% CI, 1.66-2.65), pelvic (HR, 1.66; 99% CI, 1.26-2.20), and hip (HR, 1.50; 99% CI, 1.30-1.74) fractures. Associations persisted after oral glucocorticoid adjustment.

Conclusions: People with atopic eczema have increased fracture risk, particularly major osteoporotic fractures.

Keywords: Atopic eczema; fracture; osteoporosis; population based; severity.

Graphical abstract

Fig 1

Graphic depiction of the study population. CPRD, Clinical Research Practice Datalink; GP, general practitioner.

Fig 2

Flow chart illustrating identification of study populations. Note: The number of participants in both the atopic eczema and matched cohorts do not add up to the total number of study participants because participants can contribute follow-up time both with and without atopic eczema.

Fig 3

Forest plot showing association (HR [99% CI] compared with those without atopic eczema) between severity of atopic eczema and fracture. *In comparison to those without atopic eczema. Minimally adjusted is defined as implicit adjustment for sex, age, general practice, and date of cohort entry. Fully adjusted is defined as additional adjustment for time-updated asthma, IMD, and calendar time. Addition of possible mediators is defined as further adjustment for BMI, smoking status, harmful alcohol use, and high-dose oral glucocorticoid use. Participants were only included if they were in a complete matched set (complete data for 1 individual with atopic eczema and ≥1 individual without atopic eczema).

Fig E1

Directed acyclic graph showing the implicitly assumed causal relationship (between atopic eczema and fracture) underlying our adjusted models. We identified possible covariates through a literature search for common risk factors for fractures and eczema. We also considered risk factors common to osteoporosis and eczema as possible covariates (because osteoporosis is a hypothesized mechanism for increased fracture risk in those with eczema).