Risk of osteoporotic fracture in patients with multiple sclerosis: The Danish National Health Registers

Background: Hip fractures carry a 12-month excess mortality of up to 20% and often represent a major drop in quality of life. Patients with MS may be at increased risk of fractures due to immobilisation, expose to glucocorticoids and greater risk of falling. Few studies have estimated fracture risks in MS patients. Objective: To evaluate the risk of fracture in patients with MS and population-based controls, stratified by drug use and expanded disability status scale (EDSS). Methods: We conducted a longitudinal population-based cohort study (1996-2007) utilising the Danish National Health Registers that were linked to the Danish MS Registry (DMSR), and the Danish MS Treatment Registry (DMSTR). DMSR is a nationwide database on approximately 90% of all cases with MS. A subset of all patients from the DMSR is also enrolled in the DMSTR. The case population consisted of all incident MS patients with an accepted diagnosis of MS in the DMSR. Patients with MS (2,931 cases) were 1:6 matched by year of birth, gender, calendar time and region to patients without MS (controls). Cox proportional hazards models and logistic regression were used to estimate risk of osteoporotic fracture in MS. Time-dependent adjustments were made for age, gender, and history of diseases and drug use. An osteoporotic fracture was defined as a fracture of the radius/ulna, humerus, rib, femur, hip, pelvis, or vertebrae. Results: Compared with controls, patients with MS had no increased risk of osteoporotic fracture: Adjusted Hazard Ratio (HR) 1.0 (95% CI 0.8-1.3). However, risks of hip fracture (HR 2.3 (95% CI 1.2-4.4)), femur fracture (HR 2.5 (95% CI 0.9-6.5)) and tibia fracture (HR 1.4 (95% CI 0.7-2.7)) were increased compared to controls. MS patients who had been exposed to antidepressants in the previous six months had a 1.6-fold increased risk of osteoporotic fracture compared to unexposed MS patients (HR 1.6 (95% CI 1.0-2.5)). MS patients who had been exposed to a shortcourse of methylprednisolone in the previous year had a 1.2-fold increased risk of osteoporotic fracture vs. untreated MS patients (HR 1.2 (95% CI 0.5-2.9)). MS patients with EDSS from 4 to 6.5 (Odds Ratio [OR] 1.9 (95% CI 0.9-4.0)) and from 7 to10 (OR 1.6 (95% CI 0.3-7.7)) had a greater risk of osteoporotic fracture than patients with EDSS 0-3.5 (reference). Conclusions: Patients with MS had a greater risk of fracture types that are related to immobility. Disability and the use of antidepressants further increased risks.