Study to Determine the Efficacy and Safety of Romosozumab in the Treatment of Postmenopausal Women With Osteoporosis

In this trial, women were randomly assigned in a 1:1 ratio to receive monthly subcutaneous
romosozumab or weekly oral alendronate for 12 months. Randomization was stratified according
to age (<75 vs. ≥75 years). After completion of the double-blind treatment period, all the
participants were to receive open-label weekly oral alendronate until the end of the trial,
with blinding to the initial treatment assignment maintained.

The primary analysis was performed when clinical fracture events had been confirmed in at
least 330 participants and all the participants had completed the month 24 visit. The study
was to continue in an event-driven manner until at least 440 participants experienced a
nonvertebral fracture or if the superiority of romosozumab was proven for nonvertebral
fractures at the primary analysis.

Inclusion Criteria:

Postmenopausal women who meet at least one of the following bone mineral density (BMD) and
fracture criteria:

- BMD T-score at the total hip or femoral neck of ≤ -2.50 and EITHER:

- at least 1 moderate (semiquantitative grade [SQ]2) or severe (SQ3) vertebral
fracture OR

- at least 2 mild (SQ1) vertebral fractures OR

- BMD T-score at the total hip or femoral neck of ≤ -2.00 and EITHER:

- at least 2 moderate (SQ2) or severe (SQ3) vertebral fractures OR

- a fracture of the proximal femur that occurred within 3 to 24 months prior to
randomization.

Exclusion Criteria:

- History of metabolic or bone disease (except osteoporosis)

- Use of agents affecting bone metabolism

- Vitamin D insufficiency

- History of solid organ or bone marrow transplants

- Hyper- or hypocalcemia

- Hyper- or hypothyroidism

- Hyper- or hypoparathyroidism

- Possible signs of intolerance to alendronate