Long-Term Effects of Rheumatoid Arthritis Treatments on Bone Mineral Density: 8-Year-Follow-Up Data from Real-World Practice

Objectives: The long-term effects of rheumatoid arthritis (RA) therapies on bone mineral density (BMD) remain incompletely characterized. We aimed to evaluate BMD trajectories over an 8-year follow-up in patients with RA treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biological DMARDs (bDMARDs) in real-world practice. Methods: Patients were selected from an observational RA cohort established at Nice University Hospital between 2001 and 2016. Participants were classified into two groups according to treatment regimen (csDMARD only or any bDMARD exposure). BMD was assessed by dual-energy X-ray absorptiometry at baseline and after 1, 2, 3, 5, and 8 years at the lumbar spine, femoral neck, and total hip. Longitudinal changes in BMD were analyzed using multivariable linear mixed-effects models adjusted for age, sex, body mass index (BMI), disease duration, seropositivity, glucocorticoid use, anti-osteoporosis treatment, and clinical response. Results: A total of 312 patients were included, of whom 181 received bDMARDs and 131 were treated exclusively with csDMARDs. BMD showed limited change during the first two years in both groups. Beyond two years, modest declines were observed at hip sites at subsequent time points, whereas lumbar spine BMD did not demonstrate significant longitudinal change in pointwise analyses. In mixed-effects models, the treatment group–time interaction was significant for lumbar spine (p = 0.004) and total hip (p = 0.04), but not for the femoral neck (p = 0.34), indicating differential BMD trajectories over time between treatment groups. In the csDMARD group, lumbar spine and total hip BMD decreased by a mean of 0.0006 and 0.0005 g/cm2 per month, respectively, whereas no significant slopes were observed in the bDMARD group. Older age was associated with lower BMD, while male sex and higher BMI were associated with higher BMD across sites. Conclusions: In this long-term real-world cohort, BMD remained relatively stable during the first two years of follow-up. Longitudinal analyses suggested a less pronounced decline in lumbar spine and total hip BMD trajectories among bDMARD-treated patients compared with those receiving csDMARD alone, underscoring the need for ongoing bone health monitoring in RA.