Fig. 7
From: NOTUM inhibition increases endocortical bone formation and bone strength
NOTUM antibody treatment increases cortical bone mass in both gonadal intact and ovariectomized mice. a In a pilot study, NOTUM antibody 2.78.33 treatment given weekly at 30 mg·kg−1 for 8 weeks increased midshaft femur cortical bone thickness in male mice (8-week-old) by (16.4 ± 1.3)% over vehicle-treated mice (P < 0.001, not shown in the figure). Two dose-response studies [study 1 (N = 10) and study 2 (N = 12) as shown in a], revealed an optimal dose of 10 mg·kg−1 given by intraperitoneal injection once weekly for 4 weeks to 8-week-old male mice. Effects on femur cortical bone thickness are shown as percent increases compared to control antibody treated mice. b–j Effects of NOTUM antibody treatment on bone parameters in sham-operated and ovariectomized (OVX at 16 weeks of age) mice. At 24 weeks, four weekly injections of NOTUM neutralizing antibody 2.78.33 (10 mg·kg−1 intraperitoneal injection) or control antibody for were initiated. b Midshaft femur cortical thickness. c Femoral neck bone volume per total volume (BV/TV; mainly reflecting cortical bone). d LV5 vertebral cortical shell BV/TV; reflecting cortical bone. e LV5 vertebral body trabecular BV/TV. f–j Dynamic histomorphometry of midshaft femur cortical bone. Mice were injected with calcein, alizarin and demeclocycline on days 7, 14, and 21, respectively. f Single-labeled endocortical surface (Ec.sLC). g Endocortical mineralized surface per bone surface (MS/BS). h Endocortical mineral apposition rate (MAR). I Endocortical bone formation rate (BFR). Values are means ± SEM (N = 11–14), *P < 0.05 and **P < 0.01 vs control
