Sickle cell mice display bone impairment, increased osteoclast activity, and suppression of osteoblastogenesis. Beneficial effects of zoledronic acid (Zol) on osteoclast activity in sickle cell mice. (A) Quantitative histomorphometry of the distal femur of healthy (AA) and sickle cell (SS) mice. Upper panel: representative undecalcified section of distal femur stained with trichrome Goldner’s stain. Lower panel: MSV, marrow star volume; NdN/TV, node number/tissue volume; NdN/Tm, node to termini ratio. Data are shown as mean ± standard deviation (SD) (n = 6); *P < .05 compared with healthy mice. (B) Bone volume (BV)/tissue volume (TV), trabecular thickness, trabecular number, and trabecular separation measured by Bone Explora Nova 3.5 image analyzer. Data are shown as mean ± SD (n = 6); *P < .05 compared with healthy mice. (C) ObS/ BS, osteoblast surface/bone surface; OS/BS, osteoid surface/bone surface; N.Oc/TA, osteoclast number/tissue area; ES/BS, Erosion surface/bone surface. Data are shown as mean ± SD (n = 6); *P < .05 compared with healthy mice. (D) Real-Time PCR analysis of Runx2, Sparc, RankL, Rank, and Il6. Data are shown as mean ± SD (n = 6); *P < .05 compared with healthy mice. (E) To assess the number of osteoprogenitors, bone marrow–derived cells were cultured in vitro under osteogenic differentiation conditions. The CFU-Ob obtained from the MSCs of AA and SS mice were stained by alizarin red (upper panel) and quantified (#CFU-Ob/dish) (lower panel); data are shown as mean ± SD (n = 3; P < .05 AA vs SS). (F) ES/BS, erosion surface/bone surface; N.Oc/TA, osteoclast number/tissue area in AA and SS mice with and without Zol treatment (100 μg/kg IP). Data are shown as mean ± SD (n = 6); *P < .05 compared with healthy mice; °P < .05 compared with vehicle-treated mice.