Fig. 2.

Orally active NOTUM inhibitors increase cortical bone thickness and strength. a–e Twelve-week-old male mice were treated with NOTUM inhibitor LP-922056 (n = 24; 10 mg·kg⁻¹ for 4 weeks by diet) or control diet (n = 24). a Midshaft femur cortical bone thickness. b Femur neck bone volume per total volume (BV/TV; %: mainly reflecting cortical bone). c Femur diaphyseal bone strength (maximum load; Max. load) measured by 4-point bending. d Vertebral body cortical shell bone volume per total volume (BV/TV; reflecting cortical bone, LV5). e Vertebral body trabecular bone volume per total volume (BV/TV; central part of vertebral body; LV5). f Femur cortical bone thickness in WT and NOTUM humanized male mice (Notum^HUM). LP-922056 treatment was given during 4 weeks at a dose of 30 mg·kg⁻¹ via diet starting at 12 weeks of age (N = 8–9). g, h Dose-response effects of LP-914822 (doses given twice daily by oral gavage for 25 days to male mice starting at 9 weeks of age, N = 13) (g) and LP-935001 (doses given by daily oral gavage for 24 days to male mice starting at 13 weeks of age, N = 12–16) (h) on femur cortical bone thickness given as % increase above vehicle-treated mice. Values are means ± SEM. **P < 0.01 vs controls