Figure 5.

Response to Pharmacologic Inhibition of Sost Is Blunted in Lrp4^KI Mice

Cortical thickness (Ct.Th.) (A) and trabecular bone volume fraction (Tb.BV/TV) (B) in the mid-diaphyseal and distal femur and fifth lumbar vertebra (L5) (C) were significantly increased in 16-week-old female Lrp4^KI and WT (+/+) mice treated with sclerostin monoclonal antibody (Scl-mAb), but the gains were more pronounced in WT mice.

(D) μCT reconstructions from the midshaft femur (upper) distal femur (middle) and vertebral body (lower) from representative +/+ and KI/KI mice treated with vehicle (−) or Scl-mAb (+). Scale bar, 1 mm.

(E) Percent change in whole-body bone mineral density (BMD) during the 4-week antibody treatment period was greater in WT mice compared with Lrp4^KI mice.

(F–H) The periosteal bone formation parameters mineralizing surface (MS/BS), mineral apposition rate (MAR), and bone formation rate (BFR/BS) were significantly increased in WT but not Lrp4KI mice in response to sclerostin antibody. Scale bar 100 μm. For all data panels, data were tested using two-way ANOVA with Lrp4 genotype and the Scl-mAb injection as main effects. Inset at the top of each graph indicates significance of the main effects and interaction (# = Lrp4 genotype p < 0.05; @ = Scl-mAb p < 0.05; † = interaction p < 0.05). When at least one term was significant, Fisher's PLSD post hoc tests were conducted and are indicated as *p < 0.05. For all panels, n = 6–10/group.

Data are presented as means ±SEM. See also Table S5.