Disease-modifying anti-rheumatic drugs and systemic glucocorticoid use and risk of vertebral fractures in axial spondyloarthropathies: a systematic review and meta-analysis.

BACKGROUND

Vertebral fractures (VFx) represent a severe and debilitating complication of axial spondyloarthropathy (axSpA), driven by a combination of systemic inflammation, osteopenia, and spinal rigidity. While biological and conventional synthetic Disease-Modifying Anti-Rheumatic Drugs (bDMARDs and csDMARDs) and glucocorticoids are pharmacological agents used in this context, their long-term impact on the risk of developing VFx remains controversial. This systematic review and meta-analysis aimed to quantitatively evaluate the association between these specific pharmacological interventions and VFx risk in patients with axSpA.

METHODS

A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science databases for relevant observational studies and clinical trials without language or date restrictions. Studies were eligible if they compared the incidence or prevalence of VFx in adult patients with axSpA exposed to bDMARDs, csDMARDs, or systemic glucocorticoids against non-exposed controls. Pooled risk ratios (RR) were calculated using fixed effects inverse variance method. Random-effects model was substituted if heterogeneity determined by I2 was > 50%.

RESULTS

Ten studies were included after full text screening and applying the inclusion criteria. The primary analysis was carried out on 17,482 patients. bDMARDs had no significant effect on VFx in axSpA patients (RR: 0.93, 95%CI 0.65-1.35) and there were no differences between TNF inhibitors and IL-17 inhibitors (p-value = 0.753). Similarly, csDMARD exposure was not related to VFx (RR: 1.01, 95%CI 0.85-1.20). However, systemic glucocorticoid administration was associated with increased risk of VFx (RR: 1.38, 95%CI 1.22-1.56).

CONCLUSION

These findings suggest that while DMARDs effectively control disease activity, they do not appear to significantly modify the risk of VFx in the axSpA population. Conversely, systemic glucocorticoid use was identified as a significant risk factor for fracture development. Clinicians should minimize glucocorticoid exposure where possible and implement proactive bone health monitoring for patients with axSpA. Key Points • DMARD use was not associated with a significant difference in vertebral fracture risk in axSpA. • There were no significant differences in vertebral fracture risk between TNF and IL-17 inhibitors in axSpA. • Glucocorticoid use was associated with a significant increase in risk of vertebral fractures in axSpA.