(A) Six-month-old, male hRANKL mice were injected with vehicle or denosumab (10 mg/kg) once every 2 weeks for a total of 4 doses (tan-shaded area) and BMD was measured by dual-energy x-ray absorptiometry at the indicated time points. (B and C) TRAP5b or CTX-1 levels were measured in serum of the same mice as in A by ELISA at the indicated time points. n = 3 mice/group. Asterisks indicate P value ≤ 0.02 by mixed-effects repeated measures model. (D) Serial BMD analysis of 10-week-old, female hRANKL mice treated as in A. (E and F) Serum TRAP5b or CTX-1 levels of the same mice as in D. *P ≤ 0.02 by mixed effects repeated measures model. Vehicle-treated mice, n = 6; denosumab-treated mice, n = 8, except for the 23 day time point, at which n = 7 mice due to depletion of 1 sample. All values are the mean ± SD.