To investigate the effects of prior treatment and the predictors of early treatment response to romosozumab (ROMO) in patients with postmenopausal osteoporosis.In this prospective, observational, multicenter study, 130 treatment-naïve patients (Naïve; n = 37) or patients previously treated with bisphosphonates (BP; n = 33), denosumab (DMAb; n = 45), or teriparatide (TPTD; n = 15) (age, 75.0 years; T-scores of the lumbar spine [LS] -3.2 and femoral neck [FN] -2.9) were switched to ROMO based on their physician's decision. Bone mineral density (BMD) and serum bone turnover markers were evaluated for six months.At six months, LS BMD changes were 13.6%, 7.5%, 3.6%, and 8.7% (P .001 between groups) and FN BMD changes were 4.2%, 0.4%, 1.6%, and 1.5% (P = .16 between groups) for Naïve, BP, DMAb, and TPTD groups, respectively. Changes in N-terminal type I procollagen propeptide (PINP; μg/L) levels from baseline → one month were 72.7 → 139.0, 33.5 → 85.4, 30.4 → 54.3, and 98.4 → 107.4, and those of isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b) (mU/dL) were 474.7 → 270.2, 277.3 → 203.7, 220.3 → 242.0, and 454.1 → 313.0 for Naïve, BP, DMAb, and TPTD groups, respectively. Multivariate regression analysis revealed that significant predictors of LS BMD change at six months were prior treatment difference (r = -3.1, P = .0027) and TRACP-5b percentage change (r = -2.8, P = .0071) and PINP value at one month (r = 3.2, P = .0021).Early effects of ROMO on the increase in LS BMD are significantly affected by the difference of prior treatment and are predicted by the early change in bone turnover markers.Early effects of ROMO on the increase in LS BMD at six months is significantly affected by the difference of prior treatment and also predicted by the early change of bone turnover markers in patients with postmenopausal osteoporosis.