Impact of cumulative exposure to high-dose oral glucocorticoids on fracture risk in Denmark: a population-based case-control study

We 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.

PURPOSE: The 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.

METHODS: 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). 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.

RESULTS: A 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.

CONCLUSION: Among 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.