Objective To evaluate the long-term efficacy of tumor necrosis factor-α(TNF-α) inhibitor (TNFi) in the treatment of ankylosing spondylitis (AS) complicated with osteoporosis (OP) and the impact on bone metabolism, bone density, and inflammatory factors. Methods The data of 158 patients with AS and OP, who were admitted to Department of Rheumatology and Immunology of The First Affiliated Hospital of Naval Medical University (Second Military Medical University) from Jan.1, 2010 to Dec.31, 2017, were retrospectively collected.The patients were divided into bisphosphonate group (n=54), TNFi group (n=58), and TNFi＋bisphosphonate group (n=46) according to the treatment methods.All patients were treated with calcium combined with calcitriol as the background treatment.After 5 years of treatment, Bath ankylosing spondylitis disease activity index (BASDAI) and Bath ankylosing spondylitis functional index (BASFI) scores were evaluated, and inflammatory indexes, bone metabolism markers, and bone mineral density were detected. Results After 5 years of treatment, the BASDAI and BASFI scores, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), TNF-α, and interleukin-17A of the TNFi＋bisphosphonate group and TNFi group were significantly lower than those before treatment (all P＜0.05); in the bisphosphonate group only ESR and CRP were significantly lower than those before treatment (both P＜0.05), and the other inflammatory indexes and BASDAI and BASFI scores showed no significant changes (all P＞0.05).The bone mineral density of the 3 groups after 5 years of treatment was significantly higher than that before treatment (all P＜0.05), and the bone mineral density of the TNFi＋bisphosphonate group was significantly higher than that of the other 2 groups (both P＜0.05).After 5 years of treatment, the levels of parathyroid hormone (PTH), procollagen type 1 N-terminal propeptide (P1NP) and β-C-terminal telopeptide of type Ⅰ collagen (β-CTX) in the TNFi＋bisphosphonate group and bisphosphonate group were significantly decreased compared with those before treatment (all P＜0.05), while the levels of N-terminal midfragment of osteocalcin (N-MID) and 25-hydroxy-vitamin D (25VitD) were significantly increased (all P＜0.05); in the TNFi group only PTH and P1NP levels were significantly decreased (both P＜0.05), while β-CTX, N-MID and 25VitD levels showed no significant differences (all P＞0.05). Conclusion Long-term use of TNFi in patients with AS and OP can effectively reduce disease activity, improve physical function, decrease the level of inflammatory factors, alleviate abnormal bone metabolism, and increase bone mineral density; and the combined use of TNFi and bisphosphonates has better efficacy.