The objectives of the study were to determine the 2 year rate of bone changes in patients with ankylosing spondylitis (AS) and, whether bone loss is related to physical impairment, systemic inflammation. and therapy. Consecutive outpatients fulfilling the modified New York criteria for AS were included. Baseline assessment included age, disease duration, treatment, clinical, radiologic and laboratory data. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were determined every 6 months. Persistent systemic inflammation was defined as mean ESR > or = 28 mm/h or mean CRP > or = 15 mg/l. Bone mineral density (BMD) at the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry, at baseline and year 2. Statistical analysis compared the baseline and 24 month follow-up BMD data, and determined whether baseline data, and persistent systemic inflammation during the 2 years, were related to the 24 month percentage changes in BMD. Fifty-four patients (35 men, 19 women; mean age 37.3 +/- 11.3 years, mean disease duration 12.4 +/- 8.6 years) were included. After 2 years, BMD did not change at the lumbar spine (+0.75% +/- 3.5, p = 0.23), and decreased at the femoral neck (-1.6% +/- 4, p = 0.006). The 24 month percentage change in femoral neck BMD was related to persistent systemic inflammation, defined using ESR (mean percentage change -4.1% +/- 5.7 and -1.2% +/- 3.9 in patients with and without persistent inflammation; respectively; p = 0.007). These results suggest that persistent inflammation might be an etiologic factor of bone loss in AS.