(Young Investigator Award) risk of fracture in patients with multiple sclerosis: A population-based cohort study

Introduction: Patients with multiple sclerosis (MS) are at increased risk of falling, osteoporosis and are more often exposed to oral/intravenous glucocorticoids (GCs), and antidepressants compared to the general population. The risk of fracture has not yet been determined in patients withMS, versus healthy controls. Objective was to evaluate the risk of fracture in patients with MS and population-based controls. Methods: We conducted a longitudinal population-based cohort study in the UK General Practice Research Database (GPRD) that was linked to the national hospital registry of England (2001-2009). Cox proportional hazards models were used to estimate the hazard ratio (HR) of fracture in MS patients (n=5,565) versus healthy controls. Timedependent adjustments were made for age, gender, smoking, and history of diseases and drug use. Information on steroid exposure during MS relapses was retrieved from anonymised free-text. Discussion: Of all MS patients, 394 experienced a fracture during follow-up. Compared with controls, patients with MS had a 1.2-fold increased risk of any fracture: adjusted HR 1.2 (95% CI 1.1-1.4). The HR of osteoporotic fracture was 1.4 (95% CI 1.2-1.7), and the HR of hip fracture was 2.9 (95% CI 1.9-4.4). The increases in risks of fracture were larger in patients who had been treated with oral/ intravenous glucocorticoids (GCs) or antidepressants in the previous 6 months: HR of osteoporotic fracture was 1.8 (95% CI 1.4-2.4) in antidepressant users and 1.8 (95% CI 1.1-2.9) in GC users. The risk with GC in MS patients was related to daily dose: HR 1.1 (95% CI 0.5-2.6) with =7.5 mg prednisone equivalents per day. Patients who had been prescribed a methylprednisolone booster in the previous six months had a 2.1-fold increased risk of osteoporotic fracture: adjusted HR 2.1 (95% CI 0.8-5.6). Conclusion: Fracture risk assessment may be indicated in patients with MS who have been prescribed oral/intravenous glucocorticoids or antidepressants. The risk of fracture has never been determined in a population that has been exposed to both intravenous and oral glucocorticoids.