Inhibition of vascular endothelial growth factor in young adult mice causes low bone blood flow and bone strength with no effect on bone mass in trabecular regions

Objective: To determine the effect of an antibody to vascular endothelial growth factor (VEGF) on bone blood flow, bone strength, and bone mass in the young adult mouse. Methods: Ten-week-old male BALB/cJ mice were body weight-randomized into either a rodent anti-VEGF monoclonal antibody (anti-VEGF, B20-4.1.1; 5 mg/kg 2x/wk.; n=12) group or a vehicle (VEH; n=12) group. After 42 days, mice were evaluated for bone blood flow at the distal femur by F-18-NaF-PET/CT and then necropsied. Samples from trabecular and cortical bone regions were evaluated for bone strength by mechanical testing, bone mass by peripheral quantitative computed tomography (pQCT), and micoarchitecture (MicroCT). Hydration of the whole femur was studied by proton nuclear magnetic resonance relaxometry (H-1 NMR). Results: Distal femur blood flow was 43% lower in anti-VEGF mice than in VEH mice (p=0.009). Ultimate load in the lumbar vertebral body was 25% lower in anti-VEGF than in VEH mice (p=0.013). Bone mineral density (BMD) in the trabecular region of the proximal humeral metaphysis by pQCT, and bone volume fraction and volumetric BMD by MicroCT were the same in the two groups. Volume fraction of bound water (BW) of the whole femur was 14% lower in anti-VEGF than in VEH mice (p=0.003). Finally, BW, but not cortical tissue mineral density, helped section modulus explain the variance in the ultimate moment experienced by the femur in three-point bending. Conclusion: Anti-VEGF caused low bone blood flow and bone strength in trabecular bone regions without influencing BMD and microarchitecture. Low bone strength was also associated with low bone hydration. These data suggest that bone blood flow is a novel bone property that affects bone quality.