The objectives of the study were to assess the 2 year BMD changes and their determinants in patients with early inflammatory back pain suggestive of axial spondyloarthritis (SpA) (DESIR cohort). A total of 265 patients (54% male, mean age 34.4 years) had BMD measurements at baseline and at 2 years. Low BMD was defined as a Z score ≤-2 (at at least one site) and significant bone loss was defined by a decrease in BMD ≥0.03 g/cm(2). Clinical, biological and imaging parameters were assessed over 2 years. Thirty-nine patients (14.7%) had low BMD at baseline; 112 patients (42.3%) had a 2 year significant bone loss. One hundred and eighty-seven (70.6%) used NSAIDs at baseline and 89 (33.6%) received anti-TNF therapy over 2 years. In anti-TNF users, BMD significantly increased at the lumbar spine and did not change at the hip site from baseline. In multivariate analysis, baseline use of NSAIDs [odds ratio (OR) 0.38, P = 0.006] had a protective effect on hip bone loss. In patients without anti-TNF treatments, baseline use of NSAIDs (OR 0.09, P = 0.006) and a 2 year increase in BMI (OR 0.55, P = 0.003) had protective effects on hip bone loss, whereas a 2 year increase in fat mass was associated with hip bone loss (OR 1.18, P = 0.046). Among patients with symptoms suggestive of early axial SpA, 42.3% of patients have significant bone loss over 2 years. Anti-TNF therapy is protective against bone loss and baseline use of NSAIDs has a protective effect on hip bone loss.