Abstract
Summary
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.
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Acknowledgments
The authors are indebted to Manitoba Health for the provision of data (HIPC File No. 2007/2008-49). The results and conclusions are those of the authors, and no official endorsement by Manitoba Health is intended or should be inferred. This article has been reviewed and approved by the members of the Manitoba Bone Density Program Committee. WD Leslie had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the analysis.
Conflicts of Interest
The authors declare no potential conflicts of interest with respect to this work. No external funding source was required for this research. SRM receives salary support from the Alberta Heritage Foundation for Medical Research—AIHS (Health Scholar) and holds the Endowed Chair in Patient Health Management (Faculties of Medicine and Dentistry and Pharmacy and Pharmaceutical Sciences, University of Alberta). SNM is chercheur-clinicien boursier des Fonds de la Recherche en Sante du Quebec. LML is supported by a Manitoba Research Chair.
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Majumdar, S.R., Morin, S.N., Lix, L.M. et al. Influence of recency and duration of glucocorticoid use on bone mineral density and risk of fractures: population-based cohort study. Osteoporos Int 24, 2493–2498 (2013). https://doi.org/10.1007/s00198-013-2352-3
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DOI: https://doi.org/10.1007/s00198-013-2352-3