Ankylosing spondylitis and the risk of fracture: results from a large primary care-based nested case control study

Background and Aims: Ankylosing spondylitis (AS) is associated with bone loss in the vertebrae and an increased prevalence of vertebral fractures, but literature about the magnitude of the risk of fracturing is limited. One retrospective cohort study provided evidence of an increased risk of clinical vertebral fractures but not for non-vertebral fractures. This study further explores the risk of clinical vertebral and non-vertebral fractures in a large population database. Methods: In a primary care-based nested case-control study, 231,778 fracture cases and 231,778 age- and sex-matched controls were recruited. A history of AS was assessed from the medical records. AS was diagnosed in a total of 758 people. Odds ratios (OR) and 95% confidence intervals (CI) were calculated after adjustment for medication, other illnesses, smoking and body mass index whenever known. Results: The prevalence of AS was 0.18% in fracture cases and 0.15% in controls. Patients with AS had an increased risk of clinical vertebral fracture (OR: 3.26; CI: 1.51-7.02). The risk for forearm and hip fracture was not significantly increased (OR: 1.21 [CI: 0.87-1.69] and 0.77 [CI: 0.43-1.37], respectively). The risk of any clinical fracture was increased in AS patients with a history of inflammatory bowel disease (IBD) (OR: 2.79, CI: 1.10-7.08), whereas it was decreased in AS patients taking non-steroidal anti-inflammatory drugs (NSAID’s) (OR: 0.65, CI: 0.50-0.84). The risk was not associated with recent back pain, psoriasis, joint replacement therapy and use of sulfasalazine. Conclusions: Patients with AS have an increased risk of clinical vertebral fracture, but not of non-vertebral fractures, while in patients with concomitant IBD the risk of any clinical fracture is increased. The mechanism by which intake of NSAID’s reduces the risk of any clinical fracture warrants further research.