Patients with RA Have Higher Risk of Fractures

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Compared with controls, patients with rheumatoid arthritis (RA) had a higher risk of fractures, which were related to bone mineral density (BMD) at baseline and over time, according to a long-term follow-up study published in Seminars in Arthritis and Rheumatism.¹ Further, worse disability, as measured by Health Assessment Questionnaire (HAQ) scores, was also linked to a higher fracture risk.

“The association between low bone mass and subsequent fractures in RA patients has been examined in different settings with variable results,” wrote a group of investigators led by Lisa Theander, a research student of rheumatology, within the Department of Clinical Sciences at Lund University, Sweden. “Through the years it has been suggested that there is a discrepancy between levels of BMD and fracture risk in RA leading to the search for supplementary explanations and risk factors that may need more attention, before we can successfully prevent fractures related to RA.”

Risk factors included falls, muscle weakness, poor balance, impaired function due to swollen or tender joints, and impaired bone quality. Regarding bone density, osteoporosis is an important additional risk factor for fractures compared with controls. Fracture risk has been shown to increase with disease duration, although the risk of fractures among patients with early RA is not often studied.²

To determine the risk of fractures among a group of patients with newly diagnosed RA—defined as a symptom duration of < 12 months—compared with controls, as well as any predictors of fractures, investigators used data from an inception cohort of 232 patients with RA. Information included repeated clinical assessment and measures of BMD from diagnosis to 10 years. Controls were identified using the national census register and fractures were identified using International Classification of Diseases (ICD) codes. The risk of fractures among RA patients compared with controls, as well as the assessment of potential fracture predictors, were assessed using Cox regression models.

A total of 163 women and 69 men, recruited between 1995 and 2005 from the Malmö University Hospital, were included in the study along with 931 age- and sex-matched controls. The mean age was 60.5 years in both cohorts and most were women (70.3% in the RA group and 70.5% in the control group). At baseline, patients reported a mean duration of symptoms of 7.4 months.

Results revealed patients with RA had an increased risk of fractures (fully adjusted hazard ratio [HR] 1.52, 95 % confidence interval [CI] 1.13; 2.06). For those experiencing their first incident fracture during the study period, the mean time to fracture was 9.6 years in the RA group and 10.0 years in the control group.

According to multivariate analyses, significant baseline predictors for future fractures included higher age (HR per standard deviation [SD] 2.20, 95 % CI 1.64; 2.94), low body mass index (sex- and age-adjusted HR per SD 0.58, 95 % CI 0.44; 0.77), and low BMD. However, baseline disease characteristics were not associated with an increased risk. Additionally, worse HAQ scores were significantly linked to an increased risk of fractures (age-sex-adjusted HR 1.33 per SD, 95 % CI 1.09; 1.63) and an inverse association between BMD Z-scores over time and fractures was observed.

Although the longitudinal design with a long-term follow-up period combined with multiple assessments strengthened the findings, investigators mentioned limitations including assessing patients diagnosed between 1995 and 2005, before biologic disease-modifying antirheumatic drugs (bDMARDs) were commonly used. Therefore, results may not be applicable to patients who were treated with bDMARDs in early disease. They also noted results should be cautiously interpreted due to the small number of fractures and baseline differences between both cohorts.

“Prediction and prevention of fractures is complex and further studies are needed to decide which risk factors of fractures are detectable already early in RA,” investigators concluded. “A combination of optimal treatment of arthritis, anti-osteoporosis therapy and, assessment of risk of falls followed by other relevant preventive measures, is probably needed to successfully prevent fractures in RA.”

References

1. ^{Theander L, Sharma A, Karlsson MK, Åkesson KE, Jacobsson LTH, Turesson C. Risk and predictors of fractures in early rheumatoid arthritis - A long term follow up study of an inception cohort. Semin Arthritis Rheum. Published online June 27, 2024. doi:10.1016/j.semarthrit.2024.152497}
2. ^{S. Jin, E. Hsieh, L. Peng, et al. Incidence of fractures among patients with rheumatoid arthritis: a systematic review and meta-analysis. Osteoporos Int, 29 (2018), pp. 1263-1275, 10.1007/s00198-018-4473-1}