(A, C, E, G, and I) Representative micrographs of von Kossa-stained sections at 8 weeks for (A) Carrier, (C) Carrier ZA, (E) OP-1 and saline, (G) OP-1 ZA, and (I) OP-1 ZA 2W. Increases in callus size, BV/TV, and are evident in both ZA + OP-1 treatment groups (magnification, ×). (B, D, F, H, and J) Representative micrographs of Goldner's trichrome-stained sections at 8 weeks for (B) Carrier, (D) Carrier ZA, (F) OP-1 and saline, (H) OP-1 ZA, and (J) OP-1 ZA 2W. OP-1 + ZA-treated samples showed fracture gap union with significantly increased callus formation over OP-1 + saline (magnification, ×). Note that Carrier and Carrier ZA groups did not heal the gap, which contains fibrous tissue.
Baseline body weight and body composition (fat and lean mass) were similar in both groups (all p > ; Supplemental Table [link] ). At the end of the study, body weight was increased in espindolol-treated animals, while it decreased in the placebo group ( p < ; Fig. 1 ). However, the observed effect on overall body weight was small, a gain of ± % (espindolol) vs a loss of ± % (placebo, p < ; Fig. 1 ). In contrast, the change in body composition was profound, lean body mass progressively increased in the espindolol group, while a small, but progressive loss of lean mass was observed in the placebo group ( p < ; Fig. 1 ). Both groups lost fat mass during the study, with a more pronounced loss of fat mass in the espindolol-treated group ( p < ; Fig. 1 ). Lean body mass increased by ± % in the espindolol group vs baseline ( p < ), while the placebo group lost ± % (Fig. 1 ). Fat mass decreased by ± % in the espindolol group vs ± % in the placebo group ( p < vs placebo; Fig. 1 ).