A Study of Romosozumab in Women With Multiple Myeloma and Osteoporosis

Inclusion Criteria:

Documented MM per International Myeloma Working Group diagnostic criteria (evidence of myeloma defining event attributed to underlying plasma cell disorder): i. Clonal plasma cells in the bone marrow ≥ 10% or presence of a biopsy proven plasmacytoma; and ii. Any one or more of the following myeloma defining events:

Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder:

Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL)
Renal insufficiency: creatinine clearance < 40 mL/min or serum creatinine 177µmol/L (>2 mg/dL)
Anemia: hemoglobin > 2 g/dL below the lower limit of normal, or a hemoglobin value <10 g/dL
Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET/CT
Clonal bone marrow plasma cell percentage ≥ 60%; or
Involved: uninvolved serum free light chain (FLC) ratio ≥ 100 (involved FLC level be ≥ 10 mg/dL; or
>1 focal lesion on MRI studies (at least 5 mm in size)
Presence of lytic bone lesion(s) due to MM based on radiographic evidence with at least one measurable lesion (≥0.5 cm in its largest diameter by computerized tomography [CT])
Postmenopausal female, defined as last menstrual cycle at least 12 months prior to study enrollment

Must have one of the following:

osteoporosis on dual X-ray absorptiometry (DXA) scan; or
fragility fracture of the spine or hip; or
morphometric spine fracture; or
osteopenia with elevated risk of fracture (calculated by the FRAX online calculator)
Within 12 months prior to study entry, ≤ 4 doses of prior intravenous bisphosphonate with the last dose ≥ 3 months prior to study entry.
Prior oral bisphosphonates are allowed if the last dose was ≥ 3 months prior to study entry.
Signed informed consent form(s). Individuals with impaired decision-making capacity may enroll if legally authorized representatives consent on behalf of individuals with impaired decision-making capacity.
Ability to comply with all study-related procedures in the investigator's judgment
18 years of age or older

Exclusion Criteria:

Assigned male at birth
Received denosumab within 12 months prior to study entry
Received teriparatide or other PTH analog use within 12 months prior to study entry
Receiving concurrent antiresorptive therapy
History of cardiovascular event (myocardial infarction and/or stroke) within the past 12 months of study entry
History of non-healed dental or oral surgery
History of osteonecrosis of the jaw
25 (OH) vitamin D levels < 20 ng/mL. Vitamin D repletion will be permitted and subjects may be rescreened once 25 (OH) vitamin D level ≥ 20 ng/mL.
Current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range per institutional standard (<8.5 or >10.5 mg/dL).