Influence of recency and duration of glucocorticoid use on bone mineral density and risk of fractures: population-based cohort study

Abstract

Although systemic glucocorticoids are commonly used, it is difficult to obtain accurate exposure history. In 50,000 patients, we confirmed that glucocorticoids were associated with reductions in bone mineral density (BMD) and increases in fracture and documented that recent and prolonged durations of exposure were particularly associated with adverse events-dose information did not improve risk prediction.

Introduction: Systemic glucocorticoid use, defined as ever having taken supra-physiologic doses for 90-days or more, is a risk factor for low BMD and fractures. This definition does not distinguish recent (vs remote) exposure.

Methods: Within a population-based clinical BMD registry in Manitoba, Canada, we identified all adults over age 40 years tested between 1998 and 2007 and then undertook a cohort study. We identified all oral glucocorticoid dispensations from 1995 to 2009 and stratified exposure by timing ("recent" if within 12 months vs "remote") and duration (short [<90 days] vs prolonged [≥90 days]). Osteoporosis-related risk factors and treatments and major fractures were obtained using administrative health data.

Results: A total of 12,818 of 52,070 (25%) subjects had used glucocorticoids prior to BMD testing; the most common exposure was remote short (n = 6453) vs recent prolonged (n = 2896) vs recent short (n = 2644) vs remote prolonged (n = 825). Compared to 39,252 never-users, only recent prolonged glucocorticoid use was significantly associated with femoral neck T-score (ANCOVA-adjusted difference -0.13, 95% CI -0.16 to -0.10, p < 0.001). There were 2,842 major (566 hip) fractures over median 5-year follow-up. Compared with never-users, only recent prolonged glucocorticoid use was significantly associated with BMD-independent increases in risk of incident major fracture (5.4 vs 7.7%, adjusted HR 1.25, 95% CI 1.07-1.45, p = 0.004) and hip fracture (1.1 vs 1.8%, adjusted HR 1.61, 95% CI 1.18-2.20, p = 0.003).

Conclusions: Recent and prolonged glucocorticoid use (but neither remote nor recent short courses) was independently associated with reduced BMD and increased risk of fractures. These findings should permit clinicians to identify a high-risk group of patients that might benefit from osteoporosis prevention.