Effects of Denosumab on the Pharmacokinetics of Etanercept

Inclusion Criteria:

- Postmenopausal women (postmenopausal is defined as no vaginal bleeding or spotting
for at least 12 months)

- Low bone mineral density (BMD) as determined by screening BMD T-scores of the lumbar
spine (L1 to L4), or total evaluable vertebrae (if fewer than L1 to L4), or total hip
≤ -1.0

- Receiving a 50-mg dose of etanercept once weekly ≥ 6 months prior to screening and
expected to continue etanercept treatment at this dose and frequency through EOS

- If currently taking methotrexate (MTX), receiving a stable dose (7.5 to 20 mg/week)
of MTX ≥ 8 weeks prior to screening

- Willing and able to take ≥ 1,000 mg elemental calcium and ≥ 400 IU vitamin D daily
upon enrollment

Exclusion Criteria:

- Type 1 diabetes; OR poorly controlled Type 2 diabetes (hemoglobin A1c (HbA1c) > 8.0%
at screening; HbA1c ≤ 8.0% within 6 months of screening is acceptable if supporting
laboratory documentation is available)

- History of heart failure, coronary artery bypass graft, or cardiac arrhythmia; OR
history of acute coronary syndrome

- Comorbid autoimmune disease, demyelinating disease, or hematologic abnormalities

- History of joint replacement in hand and/or wrist; OR history of fused joint in hand
and/or wrist

- Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw; OR
active dental or jaw condition that requires oral surgery, or non-healed dental/oral
surgery; OR planned invasive dental procedure(s) during the course of the study

- Previous exposure to denosumab