Salliot et al examine the relationship between female sex hormone exposure and risk of RA in a large cohort of French women. Based on a biannual questionnaire, 698 RA cases were diagnosed among 78,452 women and examined for association with endogenous and exogenous sex hormone exposure (e.g., age at menarche, parity, age at menopause, use of oral contraceptives, and use of hormone replacement therapy). Early age at menopause (≤45 vs >53 years) and early age at first pregnancy (<22 vs ≥27 years) were associated with increased risk of incident RA. Among exogenous hormone exposure, duration of perimenopausal progestogen use >24 months was inversely associated with risk of RA (HR 0.77). The results of this study are difficult to fit into a simple narrative regarding cumulative hormonal exposure or lifetime reproductive events, and the hazard ratios in question are relatively low. Even taking into account the fact that the study only looked at RA incidence after menopause, a larger cohort size may be necessary to determine whether type and timing of hormone exposure influences RA risk.
New biomarkers remain of high interest in RA in order to better predict severity and tailor treatment. ACPA positivity is known to be associated with joint damage in RA; however, ACPA-negative RA patients have similar outcomes in terms of pain and fatigue. Lamachia et al analyze the predictive value of anti-carbamylated protein (anti-CarP) and anti-peptidyl-arginine deiminase type-3 (anti-PAD3) antibodies in identifying patients at risk of severe RA outcomes. Anti-PAD3, but not anti-CarP, positivity was associated with higher baseline swollen joint counts and DAS28-ESR, as well as higher overall disease activity and joint damage scores, but not radiographic progression. While there was significant overlap between RF- and ACPA-positive and anti-PAD3 positive RA patients, the existence of a subset of nearly 20% of anti-PAD3 positive patients who were anti-CCP3 negative suggests that anti-PAD3 could have diagnostic in addition to predictive utility.
In addition to risk of joint damage, people with RA also have an increased risk of fracture due to low bone density, glucocorticoid use, and other factors. While we may recognize this in older patients, the risk in younger patients may be less frequently recognized. In this retrospective cohort study, Erwin et al examined risk of fracture and risk of first fracture before age 50 in RA patients compared to matched controls. Overall, fracture risk was higher in RA patients even after adjusting for age at diagnosis, gender, glucocorticoid risk, smoking, and alcohol use. Women in particular had a higher risk of first fracture before age 50 compared to women without RA; men did not have a similar risk. Hopefully awareness of this increased risk among younger RA patients will lead to better preventative strategies as well.