Background/Purpose: Individuals with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are at increased risk for osteoporosis and fragility fractures due to long-term glucocorticoid (GC) use and underlying Interleukin-6 (IL-6)–driven inflammation. IL-6 inhibition is an effective treatment that also reduces GC exposure. In rheumatoid arthritis, IL-6 receptor blockade with tocilizumab reduces bone resorption markers and increases femoral neck bone mineral density (BMD). However, longitudinal data on the effects of IL-6 blockade on bone health in large-vessel vasculitis are lacking, and no study has yet compared its impact to methotrexate (MTX) or GC monotherapy.This study aimed to compared the effects of IL-6 inhibition, MTX and GC monotherapy on bone health in patients with GCA and PMR.

Methods: This longitudinal analysis uses data from the prospective Rh-GIOP study at Charité–Universitätsmedizin Berlin (2015–2024). Patients with GCA or PMR undergoing osteoporosis checkup were included up to the second follow-up visit. Bone health was assessed using dual-energy X-ray absorptiometry (DXA), trabecular bone score (TBS), 3D structural femur parameters (3D-Shaper v2.12), and bone turnover markers (bone-specific alkaline phosphatase, osteocalcin and desoxypyridinoline [DPD]).Linear mixed-effects models were used to assess associations between treatment (IL-6 inhibitors, MTX, GC monotherapy) and bone outcomes, adjusting for age, sex, BMI, GC dose, erythrocyte sedimentation rate (ESR), prior fragility fractures, and anti-osteoporotic therapy. Estimated marginal means compared adjusted group differences.

Results: A total of 203 patients (81 with GCA; mean age 72 years; 66% female, all postmenopausal) were included. At baseline visit for osteoporosis check-up 22 received IL-6 inhibitors (21 tocilizumab, 1 Sarilumab), 36 MTX, and 131 GC monotherapy; 14 received no immunosuppressive treatment. Seventy-five patients had at least one follow-up visit (mean follow-up: 2.6 ± 1.3 years), and 27 had a second (4.6 ± 1.3 years). Osteoporosis by DXA and fragility fracture prevalence at baseline were 20% and 36%, respectively. Baseline characteristics were balanced across treatment groups.Male sex and higher BMI were positively associated with lumbar spine T-scores (estimate: +1.427, SE: 0.235, p < .005; and +2.754, SE: 0.028, p = .007), femoral T-Scores and bone structure. Higher age correlated with increased DPD levels (+0.071, SE: 0.036, p = .048).No significant overall effect was observed for IL-6 inhibitors, MTX, or GC treatment. However, compared to IL-6 inhibitors, GC monotherapy was associated with lower cortical volumetric BMD (−20.38, SE: 9.41, p = .036) and integral vBMD (−13.9, SE: 4.96, p = .006). No significant differences were found between IL-6 inhibitors and MTX, nor between MTX and GC monotherapy.

Conclusion: In patients with GCA and PMR, sex and BMI were key predictors of BMD and femoral bone structure. Treatment with IL-6 inhibitors was associated with more favorable cortical and trabecular bone parameters than GC monotherapy. This suggests that GC-sparing IL-6 blockade may help preserve bone microarchitecture in patients with inflammatory vasculitis.

Table 1: Patient characteristics at baseline. Comparison of confounder variables between treatment groups.

MTX: methotrexate; GC: glucocorticoids; BMI (body mass index); CRP: C-reactive protein; ESR: erythrocyte sedimentation rate

Table 2: Estimated marginal means (EMM) for the comparison between GC monotherapy and IL-6 inhibition

vBMD: volumetric bone mineral density

ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparative-effects-of-il-6-inhibition-methotrexate-and-glucocorticoid-monotherapy-on-bone-mineral-density-3d-dxa-femoral-structure-and-bone-turnover-markers-in-gca-and-pmr/