Abstract
PurposeTo evaluate the effects of different definitions of glucocorticoid (GC) exposure on the magnitude and pattern of fracture risk using the same dataset.MethodsData from patients with rheumatoid arthritis (RA) were extracted from the Clinical Practice Research Datalink, a primary care database with electronic health records in the United Kingdom. Patients exposed to oral GCs were matched to up to two unexposed patients by age, gender and location. The first osteoporotic fracture was identified and adjusted and unadjusted cox proportional hazard ratios (HR) and 95% confidence intervals (CI) produced for fracture risk following GC therapy using different models of risk attribution. These include models demonstrating the effect of dose, duration and recency of GC exposure.ResultsThere were 16,507 patients included. Exposed patients were older and had more comorbidities. GC therapy was associated with an increased risk of fracture, with the effect size influenced by risk attribution model. The risk of fracture decreased with less recent exposure from HR (95% CI) 1.66 (1.27, 2.16) during the first month of stopping GCs to 1.11 (0.79, 1.57) for between 1 and 3 months. The risk of fracture increased with current daily dose, HR 1.44 (1.17, 1.77) for 5–9.9 mg prednisolone equivalent dose (PEQ) to 3.02 (1.77, 5.15) for 15–19.9 mg PEQ. Risk of fracture increased with cumulative dose, a function of dose and duration, from HR 1.22 (1.03, 1.44) for <1 g to 1.83 (1.35, 2.48) for 7.5–10 g.ConclusionGC exposure was associated with excess fracture risk, with effect size differing according to definition of exposure. This highlights the need to incorporate all exposure dimensions (dose, duration and recency) in these patient's fracture risk assessments.
Highlights
Glucocorticoids (GCs) have been used for over 65 years as an antiinflammatory treatment for patients with rheumatoid arthritis (RA) [1]
For the second matched patient, 30% were of the same age, 4% were in the same practice and 58% were within the same region
We have shown in Model 2 that does between 15 and 19.9 mg per day prednisolone equivalent dose (PEQ) were associated with three-fold increase in fracture risk whilst a hazard ratios (HR) of 1.52 was seen for patients taking between 10 and 14.9 mg per day compared to non-use
Summary
Glucocorticoids (GCs) have been used for over 65 years as an antiinflammatory treatment for patients with rheumatoid arthritis (RA) [1]. They rapidly reduce inflammation and improve associated symptoms such as pain [2]. Oral GCs are used at least once by around half of RA patients, with 13% using them continuously for more than a year [3]. GCs have been associated with a number of adverse effects include diabetes, serious infection and fracture [4]. Fractures are a common adverse effect of oral GCs and carry substantial health burden and economic cost [5].
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