Abstract: Proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) might be, at least partially, responsible for the development of osteopenia or osteoporosis in Crohn's disease. We investigated whether anti-TNF therapy for Crohn's disease could have any skeletal impact. Therefore, we studied the effects of infliximab, a monoclonal antibody against TNF-α with and without bisphosphonates, on spinal bone mineral density (BMD). The effect of corticosteroids was also analyzed. A retrospective cohort analysis was performed on 61 patients with Crohn's disease and low BMD by serial DXA scans. Twenty-three patients were on infliximab and 36 patients were on bisphosphonates. Mean duration between DXA scans was 2.2 ± 0.99 years. After controlling for corticosteroid use, patients with concurrent infliximab and bisphosphonate treatment exhibited a greater increase in BMD compared to those on bisphosphonates alone (+6.7%/year vs. +4.46%/year, P= 0.045); corticosteroids inhibited this effect (P= 0.025). However, infliximab alone had no effects on BMD. Patients receiving bisphosphonates showed a significant increase in lumbar spine BMD compared to those not on bisphosphonates (+3.97% change in T score/year vs. −3.68%/year, P < 0.0001). Concurrent corticosteroid use significantly inhibited this effect (+2.15%/year vs. +4.97%/year, P= 0.0014). Concurrent infliximab use may confer an additional benefit to that already documented for bisphosphonate use alone; bisphosphonates are beneficial in the treatment of low BMD in patients with Crohn's disease, though corticosteroids may partially inhibit this effect.