Epo treatment results in a substantial decrease in trabecular bone and increased bone remodeling. (A) Three-dimensional μCT analysis of the secondary spongiosa of proximal tibia depicting a representative top view (top) and side view (bottom) from PBS- and Epo-treated mice, respectively (n = 12 per treatment). (B) Representative sections (original magnification ×25) of 2-dimensional histomorphometric analysis of the same tibial region as in panel A on fixed, plastic-embedded 5-μm sections, stained with (B) Goldeners trichrome, (C-K) toluidine blue, or (L-M) xylenol orange. The box represents the region measured for histomorphometry. Histologic analysis quantification of (C) percentage of bone volume per total volume (BV/TV), (D) trabecular number (Tb.N), (E) trabecular separation (Tb.Sp), and (F) trabecular thickness (Tb.Th). Further quantification of the (G) numbers of osteoclasts per bone perimeter (N.Oc/B.Pm), (H) percentage of bone surface occupied by osteoclasts (Oc.S/BS), (I) numbers of osteoblasts per bone perimeter (N.Ob/B.Pm), and (J) percentage of bone surface occupied by osteoblasts (Ob.S/BS). (K) Quantification of the percentage of unmineralized osteoid volume per bone volume (n = 11 treatment). (L-M) Double-fluorochrome labeling with calcein depicted as (L) mineral appositional rate (MAR), (M) single labeled surface per bone surface (sL.S/BS), and (N) double-labeled surface per bone surface (dL.S/BS) (n = 8 and 11 for PBS and Epo treatment, respectively). All bones were collected 10 days after the first PBS or Epo injection. Data are presented as mean ± SEM.