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. 2022 Dec 1;13(6):1891–1900. doi: 10.14336/AD.2022.0315

Figure 3.

Figure 3.

Optimized ratio of sclerostin to Dkk1 antibody at low total dose produces equivalent improvements in bone formation parameters, compared to higher dose sclerostin antibody monotherapy, in both adult and aged mice. (A) Representative fluorochrome-labeled midshaft femur histologic cross-sections from mice treated as described for panel A. The ROI box in the left (whole bone) panels is magnified in the right (high magnification) panels to visualize bone formation between the demeclocycline (orange) label and the calcein (green)/alizarin (red) labels. See Figure 1A for labeling schedule. Deme: Demeclocyclin (orange); Cal: Calcein(green) (B) Quantification of new bone formation on the periosteal (Ps) and endocortical (Ec) surfaces, measured using the demeclocycline and calcein labels/alizarin labels, and presented as the bone formation rate per unit bone surface (BFR/BS). Mineralizing surface and mineral apposition rates appear in Supplemetary Fig. 2. (C) Quantification of serum concentration of c-terminal telopeptide (CtX) from all treatment groups at middle point of antibody treatment *p<0.05 vs. Vehicle; #p<0.05 vs. Scl-mAb alone; $p<0.05 vs 6 month Panel B: 6 month: Vehicle: n=9, Scl-mAb: n=9, Scl-mAb+Dkk1-mAb: n=9, Dkk-mAb: n=8 20 month: Vehicle: n=8, Scl-mAb: n=9, Scl-mAb+Dkk1-mAb: n=8, Dkk-mAb n=7 per group Panel C: 6 month: Vehicle: n=5, Scl-mAb: n=5, Scl-mAb+Dkk1-mAb: n=5, Dkk-mAb: n=5 20 month:Vehicle: n=5, Scl-mAb: n=5, Scl-mAb+Dkk1-mAb: n=4, Dkk-mAb n=5 per group.