Anti‐LRP6/DKK1 combination strategy reduced bone resorption in 5TGM1‐bearing mice compared to single treatment. (A) (i) Mineral apposition rate (MAR, μm/day), (ii) mineralizing surface (MS/BS, %); and (iii) bone formation rate (BFR, μm3/μm2/day) measured on trabecular surfaces within femurs of naïve or 5TGM1‐bearing mice treated with either anti‐LRP6 Ab alone, anti‐LRP6/DKK1 Ab combination, or their respective isotypes for 21 days. (B) Representative images of TRAP‐stained sections of femurs harvested from naïve mice treated with either anti‐LRP6 Ab alone, anti‐LRP6/DKK1 Ab combination, or their respective isotypes for 21 days. Small black scale bars represent 50 μm. (C) Quantification of (i) number of osteoclasts (N.Oc/BS.Pm, N/mm) and (ii) osteoclast surface (Oc.S/BS.Pm, %) per trabecular bone surfaces in each respective treatment group after 21 days of treatment. (D) Quantification of serum P1NP (ng/mL) as an indication of systemic expression of bone formation in naïve and 5TGM1‐bearing mice treated with either anti‐LRP6/DKK1 Ab combination or its isotype after 21 days of treatment. (E) Quantification of (i) number of osteoclasts (N.Oc/BS.Pm, N/mm) and (ii) osteoclast surface (Oc.S/BS.Pm, %) per endocortical bone surfaces in each respective treatment group after 21 days of treatment. (F) Quantification of serum TRAcP5b (μg/L) as an indication of systemic expression of bone resorption in naïve and 5TGM1‐bearing mice treated with either anti‐LRP6/DKK1 Ab combination or its isotype after 21 days of treatment. Results plotted as mean ± SD. Ab = antibody.