Trends in Fracture Rates Over Two Decades Among Veterans With Ankylosing Spondylitis

Abstract

Objective: There is an increased risk of fracture in individuals with ankylosing spondylitis (AS) compared to the general population, possibly due to systemic inflammatory effects. The use of tumor necrosis factor inhibitors (TNFi) may reduce fracture risk by inhibiting inflammation. We assessed fracture rates in AS versus non-AS comparators and whether these rates have changed since the introduction of TNFi.

Methods: We used the national Veterans Affairs database to identify adults ≥18 years old with ≥1 International Classification of Diseases, Ninth Revision (ICD-9)/ICD-10 code for AS and at least 1 disease-modifying antirheumatic drug prescription. As comparators, we selected a random sample of adults without AS diagnosis codes. We calculated fracture incidence rates for AS and comparators, with direct standardization to the cohort structure in 2017. To compare fracture rates from 2000 to 2002 (pre-TNFi) versus 2004-2020 (TNFi era), we performed an interrupted time series analysis.

Results: We included 3,794 individuals with AS (mean age 53 years, 92% male) and 1,152,805 comparators (mean age 60 years, 89% male). For AS, the incidence rate of fractures increased from 7.9/1,000 person-years in 2000 to 21.6/1,000 person-years in 2020. The rate also increased among comparators, although the ratio of fracture rates (AS/comparators) remained relatively stable. In the interrupted time series, the fracture rate for AS patients in the TNFi era was nonsignificantly increased compared to the pre-TNFi era.

Conclusion: Fracture rates have increased over time for both AS and non-AS comparators. The fracture rate in individuals with AS did not decrease after TNFi introduction in 2003.

Figure 1.

Flow diagram of study inclusion for the AS group. Abbreviations: AS = Ankylosing Spondylitis, RA = Rheumatoid arthritis. PsA = Psoriatic arthritis. DMARDs = Disease Modifying Antirheumatic Drugs, IST = immunosuppressive therapy + DMARD and IST included: Apremilast, Azathioprine, Chloroquine, Hydroxychloroquine, Cyclosporine, Methotrexate, Leflunomide, sulfasalazine, Mycophenolate Mofetil and Cyclophosphamide #Biologics included: Infliximab, Adalimumab, Etanercept, Golimumab, Certolizumab, Secukinumab, Ixekizumab, Ustekinumab, Rituximab, Anakinra, Abatacept, Tocilizumab and Sarilumab.

Figure 2.

Fracture rates for AS and comparators. The yellow line represents the ratio of fracture rates for AS versus non-AS comparators

Figure 3.

Results of the interrupted time series analysis for fracture rates in AS (A) versus comparators (B). The interruption period is the year 2003. The black line reflects the trend in the fractures. The red dotted line reflects the predicted fracture rate assuming that pre-TNFi era trends continued.