Hypoxia/reoxygenation stress (H/R) affects bone homeostasis in sickle cell mice. Zoledronic acid prevents H/R-induced increased turnover and osteoclast activation. (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 under normoxia and exposed to H/R stress. Data are shown as mean ± SD (n = 6); *P < .05 compared with AA; °P < .05 compared with normoxic mice. (B) N.Oc/TA, osteoclast number/tissue area; ES/BS, erosion surface/bone surface in AA and SS mice under normoxia and exposed to H/R stress. Data are shown as mean ± SD (n = 6); *P < .05 compared with AA; °P < .05 compared with normoxic mice. (C) Serum levels of bone alkaline phosphatase (bALP) and carboxy-terminal collagen crosslinks (CTX-I) in AA and SS mice under normoxia and exposed to H/R stress. Data are shown as mean ± SD (n = 6); *P < .05 compared with AA; °P < .05 compared with normoxic mice. (D) Left panel: representative images of calcein-labeled bone surface. Right panel: BRF/BS and AcF in AA and SS mice exposed to H/R stress without and with Zol treatment before (pre-Zol) or after (Zol-post) H/R stress. Data are shown as mean ± SD (n = 6); *P < .05 compared with healthy mice; °P < .05 compared with vehicle treated mice; ^P < .05 Zol-pre compared with Zol-post. (E) N.Oc/TA and ES/BS in AA and SS mice exposed to H/R stress without and with Zol treatment before (Zol-pre) or after (Zol-post) H/R stress. Data are shown as mean ± SD (n = 6); *P < .05 compared with AA; °P < .05 compared with vehicle-treated mice.