Abstract
SummaryWe examined the effect of cumulative exposure to high doses of oral glucocorticoids on fracture risk. Compared to short-course users (daily dose ≥ 15 mg + cumulative < 1 g), heavy users (daily dose ≥ 15 mg + cumulative dose ≥ 1 g) had the highest risk of fracture. These patients should be monitored for fracture management strategies.PurposeThe effect of cumulative exposure to high daily doses of oral glucocorticoids on fracture risk remains debated. We therefore aimed to examine the hip fracture risk associated with short courses and heavy use of high-dosed oral glucocorticoids.MethodsWe conducted a population-based case-control study using the Danish National Health Service data, 1996–2011. Cases were those aged ≥ 18 years who sustained a hip (primary outcome) fracture (n = 81,342). Vertebral and forearm fractures were considered in secondary analyses. Controls (matched 1:1) were those without a fracture. Average daily dose (DD) and total cumulative dose (CD) were calculated among current oral glucocorticoid users. Among patients with a high daily dose (DD ≥ 15 mg), we identified short-course users as those with a CD < 1 g and heavy users as those with a CD ≥ 1 g. We estimated adjusted odds ratio (adj.OR) of fracture with current glucocorticoid use compared to never-use, using conditional logistic regression.ResultsA high DD (≥ 15 mg) and high CD (≥ 1 g) were independently associated with an increased hip fracture risk (adj.OR 2.5; 95% CI 2.2–2.9; adj.OR 1.6; 95% CI 1.5–1.8, respectively). However, the risk was substantially increased among heavy users (DD ≥ 15 mg and CD ≥ 1 g: adj.OR 2.9; 95% CI 2.5–3.4) as compared to short-course users (DD ≥ 15 mg and CD < 1 g: adj.OR 1.4; 95% CI 1.1–1.9). Associations were stronger for vertebral fractures, yet little association was identified for forearm fractures.ConclusionAmong patients receiving a high DD (≥ 15 mg), heavy users (≥ 1 g CD) showed the most substantial increase in hip fracture risk. Among those receiving high DD, a threshold of 1 g CD may identify heavy users that are candidates for focused fracture management services.
Highlights
No dose-response of forearm fracture risk was observed (Fig. 4 and Appendix Table 3). In this population-based case-control study, we identified that heavy use of oral glucocorticoids was associated with a 3-fold increased hip fracture risk, which was substantially higher as compared to short-course users
While both the daily dose (DD) and cumulative dose (CD) were independently associated with hip fracture risk, our results suggest that hip fracture risk was modified by the CD among patients receiving a high DD of oral glucocorticoids
Our study further showed that the odds of sustaining fractures among glucocorticoid users were stronger for clinical symptomatic vertebral fracture than hip fracture, while forearm fracture risk was minimal to non-significant among current users and across dose categories
Summary
We conducted a population-based case-control study using the Danish National Health Service data, 1996–2011 Cases were those aged ≥ 18 years who sustained a hip (primary outcome) fracture (n = 81,342). Among patients with a high daily dose (DD ≥ 15 mg), we identified short-course users as those with a CD < 1 g and heavy users as those with a CD ≥ 1 g. It is estimated that oral glucocorticoids are associated with a 30 to 120% increased risk of hip fracture and 2- to 3-fold increase in vertebral fracture risk compared with non-use [14,15,16]. While it is wellknown that oral glucocorticoid-induced bone loss and fracture risk is dose-dependent [15, 17], the relationship with the cumulative exposure is less well established [15, 17]
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