Clinical studies on bone-related outcome and the effect of TNF-α blocking therapy in ankylosing spondylitis

To provide an overview of clinical trials and observational studies investigating the effect of tumor necrosis factor-alpha (TNF-α) blocking therapy on bone formation and bone loss in patients with ankylosing spondylitis (AS).

The effect of TNF-α blocking therapy on excessive bone formation or osteoproliferation remains inconclusive. Radiographic assessment of spinal osteoproliferation is complicated by the overall slow rate of progression and the high variability between individual AS patients. Multiple studies demonstrated that TNF-α blocking therapy results in a significant increase in bone mineral density (BMD) at the lumbar spine and hip. Based on bone turnover marker (BTM) analysis, this can mainly be explained by an increase in mineralization and decrease in bone resorption.

Both osteoproliferation (e.g. syndesmophytes and ankylosis of vertebrae) and excessive bone loss resulting in osteoporosis and vertebral fractures are frequently present in AS. Previous studies showed that BMD increases during TNF-α blocking therapy. Long-term follow-up in a large cohort of patients is needed to investigate whether TNF-α blockers can consolidate or stop spinal osteoproliferation and prevent vertebral fractures. Future studies should focus on the effect of these agents on bone-related outcome in AS patients with early vs. advanced disease.