Recurrent acute vaso-occlusive crisis (VOCs) increases bone turnover, downregulates osteoblastogenesis, and upregulates osteoclastogenesis in sickle cell mice. Zoledronic acid (Zol) prevents bone impairment induced by repeated VOCs. (A) Left panel: representative images of calcein-labeled bone surface. Right panel: bone formation rate (BFR/BS) and activation frequency (AcF) in healthy (AA) and sickle cell (SS) mice exposed to recurrent (Rec) acute VOCs without and with Zol. Data are shown as mean ± SD (n = 6); *P < .05 compared with healthy mice; °P < .05 compared with vehicle-treated mice. (B) Runx2, RankL, Rank, and Cathepsin k mRNA fold changes in AA and SS mice exposed to recurrent (Rec) acute VOCs without and with Zol. Two different housekeeping genes (Gapdh and β-Actin) were used to perform real-time PCR analysis. Data are shown as mean ± SD (n = 6); *P < .05; **P < .005.