Efficacy and Safety of Romosozumab Treatment in Postmenopausal Women With Osteoporosis

New vertebral fractures occurred when there was ≥ 1 grade increase from the previous grade of 0 in any vertebra from T4 to L4 using the Genant semiquantitative scoring method. The Genant semiquantitative scoring method was based on assessment of x-rays according to the following scale: * Grade 0 (Normal) = no fracture; * Grade 1 (Mild) = mild fracture, 20 to 25% reduction in vertebral height (anterior, middle, or posterior); * Grade 2 (Moderate) = moderate fracture, 25 to 40% reduction in anterior, middle, and/or posterior height; * Grade 3 (Severe) = severe fracture, greater than 40% reduction in anterior, middle, and/or posterior height.

Time frame: 12 Months

Population: Primary efficacy analysis set includes all participants who had a baseline and ≥ 1 postbaseline evaluation of vertebral fracture during the 12 months, including participants with missing baseline Genant scores whose first postbaseline spinal radiograph showed no fracture on the same vertebrae. Last observation carried forward imputation was used.

New vertebral fractures occurred when there was ≥ 1 grade increase from the previous grade of 0 in any vertebra from T4 to L4 using the Genant semiquantitative scoring method. The Genant semiquantitative scoring method was based on assessment of x-rays according to the following scale: * Grade 0 (Normal) = no fracture; * Grade 1 (Mild) = mild fracture, 20 to 25% reduction in vertebral height (anterior, middle, or posterior); * Grade 2 (Moderate) = moderate fracture, 25 to 40% reduction in anterior, middle, and/or posterior height; * Grade 3 (Severe) = severe fracture, greater than 40% reduction in anterior, middle, and/or posterior height.

Time frame: 24 months

Population: Primary efficacy analysis set includes all participants who had a baseline and ≥ 1 postbaseline evaluation of vertebral fracture during the 24 months, including participants with missing baseline Genant scores whose first postbaseline spinal radiograph showed no fracture on the same vertebrae. Last observation carried forward imputation was used.

Clinical fractures included clinical vertebral and nonvertebral fractures (excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges) that were associated with signs and/or symptoms indicative of a fracture. Clinical vertebral fractures were included regardless of trauma severity or pathologic fractures; nonvertebral fractures associated with high trauma severity or pathologic fractures were excluded.

Time frame: 12 Months

Population: Full analysis set; Last observation carried forward imputation (LOCF) was used.

Clinical fractures included clinical vertebral and nonvertebral fractures (excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges) that were associated with signs and/or symptoms indicative of a fracture. Clinical vertebral fractures were included regardless of trauma severity or pathologic fractures; nonvertebral fractures associated with high trauma severity or pathologic fractures were excluded.

Time frame: 24 Months

Population: Full analysis set; LOCF imputation was used

Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter.

Time frame: 12 Months

Population: Full analysis set

Hip fractures were defined as a subset of nonvertebral fractures including fractures of the femur neck, femur intertrochanter, and femur subtrochanter.

Time frame: 24 Months

Population: Full analysis set

A major nonvertebral fracture was a subset of nonvertebral fractures including pelvis, distal femur (ie, femur excluding hip), proximal tibia (ie, tibia excluding ankle), ribs, proximal humerus (ie, humerus excluding elbow), forearm, and hip.

Time frame: 12 Months

Population: Full analysis set

A major nonvertebral fracture was a subset of nonvertebral fractures including pelvis, distal femur (ie, femur excluding hip), proximal tibia (ie, tibia excluding ankle), ribs, proximal humerus (ie, humerus excluding elbow), forearm, and hip.

Time frame: 24 Months

Population: Full analysis set

Major osteoporotic fractures included clinical vertebral fractures and fractures of the hip, forearm and humerus. Fractures associated with high trauma severity or pathologic fractures were excluded.

Time frame: 12 Months

Population: Full analysis set

Major osteoporotic fractures included clinical vertebral fractures and fractures of the hip, forearm and humerus. Fractures associated with high trauma severity or pathologic fractures were excluded.

Time frame: 24 Months

Population: Full analysis set

A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4.

Time frame: 12 Months

Population: Primary efficacy analysis set includes all participants who had a baseline and ≥ 1 postbaseline evaluation of vertebral fracture during the 24 months, including participants with missing baseline Genant scores whose first postbaseline spinal radiograph showed no fracture on the same vertebrae. LOCF imputation was used

A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4.

Time frame: 24 Months

Population: Primary efficacy analysis set includes all participants who had a baseline and ≥ 1 postbaseline evaluation of vertebral fracture during the 24 months, including participants with missing baseline Genant scores whose first postbaseline spinal radiograph showed no fracture on the same vertebrae. LOCF imputation was used.

A nonvertebral fracture was defined as a fracture present on a copy of radiographs or other diagnostic images such as computerized tomography (CT) or magnetic resonance imaging confirming the fracture within 14 days of reported fracture image date recorded by the study site, and/or documented in a copy of the radiology report, surgical report, or discharge summary, excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges. In addition, fractures associated with high trauma severity or pathologic fractures were excluded.

Time frame: 12 Months

Population: Full analysis set

A nonvertebral fracture was defined as a fracture present on a copy of radiographs or other diagnostic images such as computerized tomography (CT) or magnetic resonance imaging confirming the fracture within 14 days of reported fracture image date as recorded by the study site, and/or documented in a copy of the radiology report, surgical report, or discharge summary, excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges. In addition, fractures associated with high trauma severity or pathologic fractures were excluded.

Time frame: 24 Months

Population: Full analysis set

A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4. A participant had multiple new or worsening vertebral fractures when there were ≥ 2 vertebrae from T4 to L4 with ≥ 1 grade increase from the previous grade. The multiple new or worsening vertebral fractures need not have occurred at the same visit.

Time frame: 12 Months

Population: Primary efficacy analysis set includes all participants who had a baseline and ≥ 1 postbaseline evaluation of vertebral fracture during the 24 months, including participants with missing baseline Genant scores whose first postbaseline spinal radiograph showed no fracture on the same vertebrae. LOCF imputation was used.

A new or worsening vertebral fracture was identified when there was a ≥ 1 grade increase from the previous grade in any vertebra from T4 to L4. A participant had multiple new or worsening vertebral fractures when there were ≥ 2 vertebrae from T4 to L4 with ≥ 1 grade increase from the previous grade. The multiple new or worsening vertebral fractures need not have occurred at the same visit.

Time frame: 24 Months

Population: Primary efficacy analysis set includes all participants who had a baseline and ≥ 1 postbaseline evaluation of vertebral fracture during the 24 months, including participants with missing baseline Genant scores whose first postbaseline spinal radiograph showed no fracture on the same vertebrae. LOCF imputation was used.

Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

Time frame: Baseline and Month 12

Population: Primary efficacy analysis set for BMD includes all randomized participants who had a baseline and ≥ 1 post-baseline evaluation at or before the time point under consideration in the study period; LOCF imputation was used.

Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

Time frame: Baseline and Month 24

Population: Primary efficacy analysis set for BMD includes all randomized participants who had a baseline and ≥ 1 post-baseline evaluation at or before the time point under consideration in the study period; LOCF imputation was used.

Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

Time frame: Baseline and Month 12

Population: Primary efficacy analysis set for BMD includes all randomized participants who had a baseline and ≥ 1 post-baseline evaluation at or before the time point under consideration in the study period; LOCF imputation was used.

Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

Time frame: Baseline and Month 24

Population: Primary efficacy analysis set for BMD includes all randomized participants who had a baseline and ≥ 1 post-baseline evaluation at or before the time point under consideration in the study period; LOCF imputation was used.

Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

Time frame: Baseline and Month 12

Population: Primary efficacy analysis set for BMD includes all randomized participants who had a baseline and ≥ 1 post-baseline evaluation at or before the time point under consideration in the study period; LOCF imputation was used.

Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

Time frame: Baseline and Month 24

Population: Primary efficacy analysis set for BMD includes all randomized participants who had a baseline and ≥ 1 post-baseline evaluation at or before the time point under consideration in the study period; LOCF imputation was used.