Romosozumab inhibits sclerostin, thereby increasing bone formation and 
decreasing bone resorption. This dual effect of romosozumab leads to rapid and 
substantial increases in areal bone mineral density (aBMD) as measured by 
dual-energy X-ray absorptiometry (DXA). In a phase 1b, randomized, double-blind, 
placebo-controlled study, romosozumab or placebo was administered to 32 women 
and 16 men with low aBMD for 3 months, with a further 3-month follow-up: women 
received six doses of 1 or 2mg/kg every 2 weeks (Q2W) or three doses of 2 or 
3mg/kg every 4 weeks (Q4W); men received 1mg/kg Q2W or 3mg/kg Q4W. Quantitative 
computed tomography (QCT) scans at lumbar (L1-2) vertebrae and high-resolution 
QCT (HR-QCT) scans at thoracic vertebra (T12) were analyzed in a subset of 
subjects at baseline, month 3, and month 6. The QCT subset included 24 
romosozumab and 9 placebo subjects and the HR-QCT subset included 11 romosozumab 
and 3 placebo subjects. The analyses pooled the romosozumab doses. Linear finite 
element modeling of bone stiffness was performed. Compared with placebo, the 
romosozumab group showed improvements at month 3 for trabecular BMD by QCT and 
HR-QCT, HR-QCT trabecular bone volume fraction (BV/TV) and separation, 
density-weighted cortical thickness, and QCT stiffness (all p<0.05). At month 6, 
improvements from baseline were observed in QCT trabecular BMD and stiffness, 
and in HR-QCT BMD, trabecular BV/TV and separation, density-weighted cortical 
thickness, and stiffness in the romosozumab group (all p<0.05 compared with 
placebo). The mean (SE) increase in HR-QCT stiffness with romosozumab from 
baseline was 26.9% ± 6.8% and 35.0% ±6.8% at months 3 and 6, respectively; 
subjects administered placebo had changes of -2.7% ± 13.4% and -6.4% ± 13.4%, 
respectively. In conclusion, romosozumab administered for 3 months resulted in 
rapid and large improvements in trabecular and cortical bone mass and structure 
as well as whole bone stiffness, which continued 3 months after the last 
romosozumab dose.