Fracture Healing
Conditions
Keywords
AMG 785, Proximal Femur, Fracture Healing, Hip Fracture
Brief summary
This is an international, multi-center study to determine the efficacy, safety, and tolerability of romosozumab (AMG 785) in adults with a fresh unilateral hip fracture, status post surgical fixation.
Interventions
DRUGPlacebo
Administered by subcutaneous (under the skin) injection
DRUGRomosozumab
Administered by subcutaneous injection
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 95 Years
Healthy volunteers
No
Inclusion criteria
* Males and females, age 55 to 95 years * fresh unilateral low energy intertrochanteric or femoral neck fracture as the primary injury, confirmed by X-ray and in the opinion of the treating surgeon amenable to repair by internal fixation * internal fixation of the fracture with devices approved by local regulatory agency, performed no later than 7 days after injury for intertrochanteric or undisplaced femoral neck fractures and no later than 2 days after injury for displaced femoral neck fractures * intertrochanteric fracture: sliding hip screw or IM nail * femoral neck fracture: sliding hip screw or at least 3 cancellous screws
Exclusion criteria
* severe symptomatic osteoarthritis of the lower extremity * inability to independently rise from armchair or walk 200 meters before hip fracture * presence of concomitant injuries such as rib fractures, wrist fractures, or acute symptomatic vertebral fractures which severely impair the ability to rise from a chair * associated extremity injuries including ipsilateral or contralateral fractures of the foot, tibia or fibula, wrist, humerus, femoral shaft, femoral head or hip dislocation, that may delay weight-bearing beyond one week after surgery * head-injury, as defined by Glasgow Coma Scale \< 13 prior to randomization * use of bone grafts or bone substitutes at the time of fracture fixation * major polytrauma or significant axial trauma, with Injury Severity Score \> 16 * pathological fracture or history of metabolic or bone disease (except osteoporosis) that may interfere with the interpretation of the results, such as Paget's disease, rheumatoid arthritis, osteomalacia, osteopetrosis, ankylosing spondylitis, Cushing's disease, hyperprolactinemia * history of symptomatic spinal stenosis that has not been surgically corrected. If surgically corrected, the subject must be asymptomatic to be eligible for the study. * history of facial nerve paralysis * malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical carcinoma in situ) within the last 5 years * history of solid organ or bone marrow transplants * evidence of elevated transaminases (≥ 2.0 x upper limits of normal) or significantly impaired renal function (creatinine clearance of ≤ 30 mL/min) * evidence of current hypercalcemia or hypocalcemia (outside of 1.1 x the normal range) * bone morphogenic proteins (BMP)-2 or BMP-7 at the time of definitive fracture fixation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 | Weeks 6, 12, 16, and 20 | Functional healing was measured by the timed-up-and-go test (TUG) over Weeks 6 through 20. During this assessment, the clinician timed the participant while they stood up from a seated position in a chair, walked three meters, turned around, walked three meters back to the chair, and returned to the seated position. A TUG value of ten seconds or less was considered normal for a healthy elderly person. Higher TUG values after hip fracture have been shown to be a predictor of future falls. Least squares mean (LSM) estimates were based on a repeated measures model fitted with the log-transformed TUG values at weeks 2, 6, 12, 16, 20, 24, 36, 52 as the dependent variable and adjusted for treatment, randomized strata, gender, country category, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction and back-transformed using the exponential transformation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Timed-Up-and-Go (TUG) at Each Visit | Weeks 2, 6, 12, 16, 20, 24, 36, and 52 | During the timed-up-and-go test the clinician timed the participant while they stood up from a seated position in a chair, walked 3 meters, turned around, walked 3 meters back to the chair, and returned to a seated position. A TUG value of ≤ 10 seconds is considered normal for a healthy elderly person. LSMs were based on a repeated measures model adjusting for treatment, randomized strata, gender, country category, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction. Missing TUG values for participants still on study were imputed using the last observation carried forward (LOCF) when possible. If no observation could be carried forward, the maximum TUG value observed among all participants at a given visit was used. TUG values obtained after unplanned revision surgery were replaced by carrying forward the last available observed or imputed value prior to unplanned revision surgery. |
| Time to Radiographic Healing | 52 weeks | Time to radiographic healing is the time interval from the surgery date for the eligible hip fracture to the date of radiographic healing, defined as effacement of the fracture lines by newly formed bone along the cortices and within the trabecular bone on anteroposterior and lateral (or oblique) radiographs. Radiographic fracture healing was determined by a panel of independent reviewers blinded to treatment. The cumulative incidence function (CIF) method was used to estimate the median time to radiographic healing and the confidence intervals. Unplanned revision surgery to promote healing was considered a competing risk in CIF estimate. |
| Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Weeks 2, 6, 12, 16, 20, 24, 36, and 52 | The radiographic Union Scale for Hip (RUSH) is a semiquantitative scoring assessment to assess hip fracture healing after surgical repair. The RUSH has 4 key domains based on radiographic parameters used by orthopedic surgeons and radiologists in routine clinical practice including cortical bridging (4 to 12 points), cortical fracture line disappearance (4 to 12 points), trabecular consolidation (1 to 3 points), and trabecular index disappearance of fracture line (1 to 3 points). The score has a minimum of 10 points (definitely not healed) and a maximum of 30 points (definitely healed). |
| Harris Hip Score At Each Visit | Weeks 2, 6, 12, 16, 20, 24, 36, and 52 | The Harris Hip Score is a clinician-based outcome that assesses pain, function, deformity, and range of motion. The pain domain measures pain severity and its effect on activities and need for pain medication. The function domain consists of daily activities and gait. Deformity takes into account hip flexion, adduction, internal rotation, and extremity length discrepancy. Range of motion measures hip flexion, abduction, external and internal rotation, and adduction. The score ranges form 0-100 (best possible outcome) covering pain (0-44 points), function (0-47 points), absence of deformity (4 points), and range of motion (5 points). LSMs were based on a repeated measures model fitted with the Harris hip score values at weeks 2, 6, 12, 16, 20, 24, 36, and 52 as the dependent variable and adjusted for treatment, randomized strata, gender, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction. |
| Hip Pain Score at Each Visit | Weeks 2, 6, 12, 16, 20, 24, 36, and 52 | Hip pain was assessed using a visual analog scale (VAS). Participants were asked to rate their pain as a result of the hip fracture on a 100 mm vertical scale with 0 indicating no pain at all and 100 indicating the worst pain they could imagine. LSMs were based on a repeated measures model fitted with hip pain score values at weeks 2, 6, 12, 16, 20, 24, 36, and 52 as the dependent variable and adjusted for treatment, randomized strata, gender, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction. |
Countries
Argentina, Australia, Belgium, Bulgaria, Canada, Denmark, Estonia, Finland, Germany, Greece, Hong Kong, Hungary, India, Italy, Latvia, Lithuania, Netherlands, New Zealand, Poland, Slovenia, Sweden, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 63 centers in 22 countries in Eastern Europe, Western Europe, India, North America, Latin America, Australia, New Zealand and Hong Kong.
Pre-assignment details
Participants were randomized in a 2:3:3:3 ratio to 1 of 3 romosozumab treatment groups or placebo. Randomization followed operative fracture repair and was stratified by type of fracture, type of fixation device and age at entry. There were 7 randomization strata.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo to romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12. | 89 |
| Romosozumab 70 mg Participants received 70 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12. | 60 |
| Romosozumab 140 mg Participants received 140 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12. | 93 |
| Romosozumab 210 mg Participants received 210 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12. | 90 |
| Total | 332 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Administrative Decision | 1 | 0 | 0 | 1 |
| Overall Study | Adverse Event | 2 | 1 | 2 | 2 |
| Overall Study | Death | 2 | 2 | 2 | 6 |
| Overall Study | Ineligibility Determined | 0 | 0 | 1 | 1 |
| Overall Study | Lost to Follow-up | 4 | 1 | 4 | 3 |
| Overall Study | Noncompliance | 3 | 4 | 5 | 2 |
| Overall Study | Other | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 15 | 7 | 17 | 14 |
Baseline characteristics
| Characteristic | Placebo | Romosozumab 70 mg | Romosozumab 140 mg | Romosozumab 210 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 76.0 years STANDARD_DEVIATION 8.6 | 76.6 years STANDARD_DEVIATION 10.3 | 75.8 years STANDARD_DEVIATION 10.1 | 76.7 years STANDARD_DEVIATION 9.5 | 76.3 years STANDARD_DEVIATION 9.5 |
| Age, Customized < 65 years | 10 Participants | 8 Participants | 17 Participants | 11 Participants | 46 Participants |
| Age, Customized ≥ 65 years | 79 Participants | 52 Participants | 76 Participants | 79 Participants | 286 Participants |
| Race/Ethnicity, Customized Asian | 12 Participants | 7 Participants | 11 Participants | 19 Participants | 49 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 77 Participants | 52 Participants | 81 Participants | 70 Participants | 280 Participants |
| Randomization Stratification Displaced femoral neck and cancellous screws | 6 Participants | 4 Participants | 6 Participants | 5 Participants | 21 Participants |
| Randomization Stratification Displaced femoral neck and SHS | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 11 Participants |
| Randomization Stratification Intertrochanteric, IM Nail and 55-75 years | 15 Participants | 10 Participants | 17 Participants | 16 Participants | 58 Participants |
| Randomization Stratification Intertrochanteric, IM Nail and ≥ 76 years | 33 Participants | 22 Participants | 34 Participants | 33 Participants | 122 Participants |
| Randomization Stratification Intertrochanteric, SHS and 55-75 years | 13 Participants | 9 Participants | 14 Participants | 14 Participants | 50 Participants |
| Randomization Stratification Intertrochanteric, SHS and ≥ 76 years | 16 Participants | 11 Participants | 16 Participants | 16 Participants | 59 Participants |
| Randomization Stratification Undisplaced femoral neck | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 11 Participants |
| Sex: Female, Male Female | 67 Participants | 42 Participants | 64 Participants | 55 Participants | 228 Participants |
| Sex: Female, Male Male | 22 Participants | 18 Participants | 29 Participants | 35 Participants | 104 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 31 / 87 | 24 / 60 | 30 / 89 | 26 / 89 |
| serious Total, serious adverse events | 25 / 87 | 9 / 60 | 15 / 89 | 26 / 89 |
Outcome results
Primary
Timed-Up-and-Go (TUG) Over Week 6 Through Week 20
Functional healing was measured by the timed-up-and-go test (TUG) over Weeks 6 through 20. During this assessment, the clinician timed the participant while they stood up from a seated position in a chair, walked three meters, turned around, walked three meters back to the chair, and returned to the seated position. A TUG value of ten seconds or less was considered normal for a healthy elderly person. Higher TUG values after hip fracture have been shown to be a predictor of future falls. Least squares mean (LSM) estimates were based on a repeated measures model fitted with the log-transformed TUG values at weeks 2, 6, 12, 16, 20, 24, 36, 52 as the dependent variable and adjusted for treatment, randomized strata, gender, country category, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction and back-transformed using the exponential transformation.
Time frame: Weeks 6, 12, 16, and 20
Population: Randomized participants who received at least one dose of study drug with available data at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 | Week 6 | 54.1 seconds |
| Placebo | Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 | Week 12 | 29.8 seconds |
| Placebo | Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 | Week 16 | 26.2 seconds |
| Placebo | Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 | Week 20 | 23.8 seconds |
| Romosozumab 70 mg | Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 | Week 12 | 27.6 seconds |
| Romosozumab 70 mg | Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 | Week 16 | 23.3 seconds |
| Romosozumab 70 mg | Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 | Week 20 | 21.9 seconds |
| Romosozumab 70 mg | Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 | Week 6 | 41.0 seconds |
| Romosozumab 140 mg | Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 | Week 16 | 26.9 seconds |
| Romosozumab 140 mg | Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 | Week 12 | 30.0 seconds |
| Romosozumab 140 mg | Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 | Week 20 | 22.9 seconds |
| Romosozumab 140 mg | Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 | Week 6 | 47.2 seconds |
| Romosozumab 210 mg | Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 | Week 20 | 29.1 seconds |
| Romosozumab 210 mg | Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 | Week 12 | 36.1 seconds |
| Romosozumab 210 mg | Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 | Week 6 | 53.3 seconds |
| Romosozumab 210 mg | Timed-Up-and-Go (TUG) Over Week 6 Through Week 20 | Week 16 | 31.8 seconds |
Comparison: The primary analysis was based on a test for linear trend in dose response at weeks 6, 12, 16, and 20. To account for multiple comparisons over time points, the primary analysis used a size α = 0.05 F-test with 4 degrees of freedom for the contrasts at Weeks 6, 12, 16, and 20.p-value: 0.1983F-test
Secondary
Harris Hip Score At Each Visit
The Harris Hip Score is a clinician-based outcome that assesses pain, function, deformity, and range of motion. The pain domain measures pain severity and its effect on activities and need for pain medication. The function domain consists of daily activities and gait. Deformity takes into account hip flexion, adduction, internal rotation, and extremity length discrepancy. Range of motion measures hip flexion, abduction, external and internal rotation, and adduction. The score ranges form 0-100 (best possible outcome) covering pain (0-44 points), function (0-47 points), absence of deformity (4 points), and range of motion (5 points). LSMs were based on a repeated measures model fitted with the Harris hip score values at weeks 2, 6, 12, 16, 20, 24, 36, and 52 as the dependent variable and adjusted for treatment, randomized strata, gender, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction.
Time frame: Weeks 2, 6, 12, 16, 20, 24, 36, and 52
Population: Randomized participants who received at least 1 dose of study drug with available data at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Harris Hip Score At Each Visit | Week 2 | 46.6 units on a scale |
| Placebo | Harris Hip Score At Each Visit | Week 6 | 58.6 units on a scale |
| Placebo | Harris Hip Score At Each Visit | Week 12 | 71.2 units on a scale |
| Placebo | Harris Hip Score At Each Visit | Week 16 | 74.1 units on a scale |
| Placebo | Harris Hip Score At Each Visit | Week 20 | 76.2 units on a scale |
| Placebo | Harris Hip Score At Each Visit | Week 24 | 79.0 units on a scale |
| Placebo | Harris Hip Score At Each Visit | Week 36 | 80.3 units on a scale |
| Placebo | Harris Hip Score At Each Visit | Week 52 | 84.3 units on a scale |
| Romosozumab 70 mg | Harris Hip Score At Each Visit | Week 24 | 80.3 units on a scale |
| Romosozumab 70 mg | Harris Hip Score At Each Visit | Week 20 | 80.2 units on a scale |
| Romosozumab 70 mg | Harris Hip Score At Each Visit | Week 6 | 62.5 units on a scale |
| Romosozumab 70 mg | Harris Hip Score At Each Visit | Week 52 | 86.7 units on a scale |
| Romosozumab 70 mg | Harris Hip Score At Each Visit | Week 36 | 82.0 units on a scale |
| Romosozumab 70 mg | Harris Hip Score At Each Visit | Week 16 | 76.5 units on a scale |
| Romosozumab 70 mg | Harris Hip Score At Each Visit | Week 12 | 70.9 units on a scale |
| Romosozumab 70 mg | Harris Hip Score At Each Visit | Week 2 | 47.7 units on a scale |
| Romosozumab 140 mg | Harris Hip Score At Each Visit | Week 36 | 86.8 units on a scale |
| Romosozumab 140 mg | Harris Hip Score At Each Visit | Week 12 | 71.7 units on a scale |
| Romosozumab 140 mg | Harris Hip Score At Each Visit | Week 16 | 76.1 units on a scale |
| Romosozumab 140 mg | Harris Hip Score At Each Visit | Week 20 | 80.5 units on a scale |
| Romosozumab 140 mg | Harris Hip Score At Each Visit | Week 24 | 83.0 units on a scale |
| Romosozumab 140 mg | Harris Hip Score At Each Visit | Week 52 | 89.0 units on a scale |
| Romosozumab 140 mg | Harris Hip Score At Each Visit | Week 2 | 47.3 units on a scale |
| Romosozumab 140 mg | Harris Hip Score At Each Visit | Week 6 | 61.6 units on a scale |
| Romosozumab 210 mg | Harris Hip Score At Each Visit | Week 12 | 69.6 units on a scale |
| Romosozumab 210 mg | Harris Hip Score At Each Visit | Week 16 | 72.8 units on a scale |
| Romosozumab 210 mg | Harris Hip Score At Each Visit | Week 6 | 59.5 units on a scale |
| Romosozumab 210 mg | Harris Hip Score At Each Visit | Week 2 | 46.5 units on a scale |
| Romosozumab 210 mg | Harris Hip Score At Each Visit | Week 20 | 77.5 units on a scale |
| Romosozumab 210 mg | Harris Hip Score At Each Visit | Week 52 | 83.8 units on a scale |
| Romosozumab 210 mg | Harris Hip Score At Each Visit | Week 36 | 83.6 units on a scale |
| Romosozumab 210 mg | Harris Hip Score At Each Visit | Week 24 | 80.1 units on a scale |
Secondary
Hip Pain Score at Each Visit
Hip pain was assessed using a visual analog scale (VAS). Participants were asked to rate their pain as a result of the hip fracture on a 100 mm vertical scale with 0 indicating no pain at all and 100 indicating the worst pain they could imagine. LSMs were based on a repeated measures model fitted with hip pain score values at weeks 2, 6, 12, 16, 20, 24, 36, and 52 as the dependent variable and adjusted for treatment, randomized strata, gender, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction.
Time frame: Weeks 2, 6, 12, 16, 20, 24, 36, and 52
Population: Randomized participants who received at least 1 dose of study drug with available data at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Hip Pain Score at Each Visit | Week 16 | 18.1 units on a scale |
| Placebo | Hip Pain Score at Each Visit | Week 2 | 34.3 units on a scale |
| Placebo | Hip Pain Score at Each Visit | Week 6 | 26.3 units on a scale |
| Placebo | Hip Pain Score at Each Visit | Week 12 | 19.4 units on a scale |
| Placebo | Hip Pain Score at Each Visit | Week 20 | 15.8 units on a scale |
| Placebo | Hip Pain Score at Each Visit | Week 24 | 13.8 units on a scale |
| Placebo | Hip Pain Score at Each Visit | Week 36 | 14.3 units on a scale |
| Placebo | Hip Pain Score at Each Visit | Week 52 | 13.4 units on a scale |
| Romosozumab 70 mg | Hip Pain Score at Each Visit | Week 24 | 9.1 units on a scale |
| Romosozumab 70 mg | Hip Pain Score at Each Visit | Week 20 | 9.2 units on a scale |
| Romosozumab 70 mg | Hip Pain Score at Each Visit | Week 6 | 19.5 units on a scale |
| Romosozumab 70 mg | Hip Pain Score at Each Visit | Week 52 | 7.2 units on a scale |
| Romosozumab 70 mg | Hip Pain Score at Each Visit | Week 2 | 33.1 units on a scale |
| Romosozumab 70 mg | Hip Pain Score at Each Visit | Week 16 | 13.5 units on a scale |
| Romosozumab 70 mg | Hip Pain Score at Each Visit | Week 12 | 17.8 units on a scale |
| Romosozumab 70 mg | Hip Pain Score at Each Visit | Week 36 | 10.9 units on a scale |
| Romosozumab 140 mg | Hip Pain Score at Each Visit | Week 6 | 25.1 units on a scale |
| Romosozumab 140 mg | Hip Pain Score at Each Visit | Week 12 | 17.5 units on a scale |
| Romosozumab 140 mg | Hip Pain Score at Each Visit | Week 16 | 16.8 units on a scale |
| Romosozumab 140 mg | Hip Pain Score at Each Visit | Week 20 | 14.0 units on a scale |
| Romosozumab 140 mg | Hip Pain Score at Each Visit | Week 24 | 12.7 units on a scale |
| Romosozumab 140 mg | Hip Pain Score at Each Visit | Week 52 | 9.3 units on a scale |
| Romosozumab 140 mg | Hip Pain Score at Each Visit | Week 2 | 40.3 units on a scale |
| Romosozumab 140 mg | Hip Pain Score at Each Visit | Week 36 | 11.6 units on a scale |
| Romosozumab 210 mg | Hip Pain Score at Each Visit | Week 6 | 27.5 units on a scale |
| Romosozumab 210 mg | Hip Pain Score at Each Visit | Week 16 | 17.4 units on a scale |
| Romosozumab 210 mg | Hip Pain Score at Each Visit | Week 12 | 23.7 units on a scale |
| Romosozumab 210 mg | Hip Pain Score at Each Visit | Week 36 | 10.2 units on a scale |
| Romosozumab 210 mg | Hip Pain Score at Each Visit | Week 20 | 15.0 units on a scale |
| Romosozumab 210 mg | Hip Pain Score at Each Visit | Week 52 | 10.4 units on a scale |
| Romosozumab 210 mg | Hip Pain Score at Each Visit | Week 2 | 43.0 units on a scale |
| Romosozumab 210 mg | Hip Pain Score at Each Visit | Week 24 | 13.1 units on a scale |
Secondary
Radiographic Union Scale for Hip (RUSH) Score At Each Visit
The radiographic Union Scale for Hip (RUSH) is a semiquantitative scoring assessment to assess hip fracture healing after surgical repair. The RUSH has 4 key domains based on radiographic parameters used by orthopedic surgeons and radiologists in routine clinical practice including cortical bridging (4 to 12 points), cortical fracture line disappearance (4 to 12 points), trabecular consolidation (1 to 3 points), and trabecular index disappearance of fracture line (1 to 3 points). The score has a minimum of 10 points (definitely not healed) and a maximum of 30 points (definitely healed).
Time frame: Weeks 2, 6, 12, 16, 20, 24, 36, and 52
Population: Randomized participants who received at least 1 dose of study drug, with available data at baseline and at each time point. Missing RUSH scores for participants who were still on study were imputed using the using last observation carried forward procedure when possible.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 2 | 12.1 units on a scale | Standard Deviation 3.3 |
| Placebo | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 6 | 18.1 units on a scale | Standard Deviation 3.6 |
| Placebo | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 12 | 23.3 units on a scale | Standard Deviation 4.6 |
| Placebo | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 16 | 25.6 units on a scale | Standard Deviation 4.3 |
| Placebo | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 20 | 26.8 units on a scale | Standard Deviation 4.1 |
| Placebo | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 24 | 27.8 units on a scale | Standard Deviation 3.4 |
| Placebo | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 36 | 28.7 units on a scale | Standard Deviation 2.6 |
| Placebo | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 52 | 29.4 units on a scale | Standard Deviation 2 |
| Romosozumab 70 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 24 | 27.8 units on a scale | Standard Deviation 3.9 |
| Romosozumab 70 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 20 | 27.3 units on a scale | Standard Deviation 4.1 |
| Romosozumab 70 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 6 | 18.0 units on a scale | Standard Deviation 4.2 |
| Romosozumab 70 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 52 | 28.5 units on a scale | Standard Deviation 3.8 |
| Romosozumab 70 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 36 | 28.3 units on a scale | Standard Deviation 3.6 |
| Romosozumab 70 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 16 | 25.7 units on a scale | Standard Deviation 4.5 |
| Romosozumab 70 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 12 | 22.8 units on a scale | Standard Deviation 4.8 |
| Romosozumab 70 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 2 | 12.7 units on a scale | Standard Deviation 3.5 |
| Romosozumab 140 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 36 | 29.1 units on a scale | Standard Deviation 2.1 |
| Romosozumab 140 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 12 | 22.9 units on a scale | Standard Deviation 4.8 |
| Romosozumab 140 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 16 | 25.5 units on a scale | Standard Deviation 5 |
| Romosozumab 140 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 20 | 27.4 units on a scale | Standard Deviation 4 |
| Romosozumab 140 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 24 | 28.3 units on a scale | Standard Deviation 3.5 |
| Romosozumab 140 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 52 | 29.6 units on a scale | Standard Deviation 1.8 |
| Romosozumab 140 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 2 | 12.1 units on a scale | Standard Deviation 3.4 |
| Romosozumab 140 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 6 | 18.4 units on a scale | Standard Deviation 3.4 |
| Romosozumab 210 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 12 | 22.3 units on a scale | Standard Deviation 5.3 |
| Romosozumab 210 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 16 | 25.5 units on a scale | Standard Deviation 4.7 |
| Romosozumab 210 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 6 | 18.3 units on a scale | Standard Deviation 4 |
| Romosozumab 210 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 2 | 12.0 units on a scale | Standard Deviation 3.1 |
| Romosozumab 210 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 20 | 26.4 units on a scale | Standard Deviation 4.6 |
| Romosozumab 210 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 52 | 28.7 units on a scale | Standard Deviation 3.3 |
| Romosozumab 210 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 36 | 28.2 units on a scale | Standard Deviation 3.5 |
| Romosozumab 210 mg | Radiographic Union Scale for Hip (RUSH) Score At Each Visit | Week 24 | 27.3 units on a scale | Standard Deviation 3.9 |
Secondary
Timed-Up-and-Go (TUG) at Each Visit
During the timed-up-and-go test the clinician timed the participant while they stood up from a seated position in a chair, walked 3 meters, turned around, walked 3 meters back to the chair, and returned to a seated position. A TUG value of ≤ 10 seconds is considered normal for a healthy elderly person. LSMs were based on a repeated measures model adjusting for treatment, randomized strata, gender, country category, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction. Missing TUG values for participants still on study were imputed using the last observation carried forward (LOCF) when possible. If no observation could be carried forward, the maximum TUG value observed among all participants at a given visit was used. TUG values obtained after unplanned revision surgery were replaced by carrying forward the last available observed or imputed value prior to unplanned revision surgery.
Time frame: Weeks 2, 6, 12, 16, 20, 24, 36, and 52
Population: Randomized participants who received at least 1 dose of study drug. LOCF imputation was used when possible, as described above.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Timed-Up-and-Go (TUG) at Each Visit | Week 20 | 36.4 seconds |
| Placebo | Timed-Up-and-Go (TUG) at Each Visit | Week 12 | 47.4 seconds |
| Placebo | Timed-Up-and-Go (TUG) at Each Visit | Week 52 | 28.7 seconds |
| Placebo | Timed-Up-and-Go (TUG) at Each Visit | Week 16 | 43.1 seconds |
| Placebo | Timed-Up-and-Go (TUG) at Each Visit | Week 36 | 32.4 seconds |
| Placebo | Timed-Up-and-Go (TUG) at Each Visit | Week 6 | 92.4 seconds |
| Placebo | Timed-Up-and-Go (TUG) at Each Visit | Week 2 | 132.3 seconds |
| Placebo | Timed-Up-and-Go (TUG) at Each Visit | Week 24 | 33.3 seconds |
| Romosozumab 70 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 16 | 31.6 seconds |
| Romosozumab 70 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 2 | 119.3 seconds |
| Romosozumab 70 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 6 | 69.5 seconds |
| Romosozumab 70 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 12 | 39.1 seconds |
| Romosozumab 70 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 20 | 31.0 seconds |
| Romosozumab 70 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 24 | 28.9 seconds |
| Romosozumab 70 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 36 | 26.3 seconds |
| Romosozumab 70 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 52 | 22.8 seconds |
| Romosozumab 140 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 6 | 80.3 seconds |
| Romosozumab 140 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 52 | 28.8 seconds |
| Romosozumab 140 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 36 | 29.8 seconds |
| Romosozumab 140 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 20 | 35.1 seconds |
| Romosozumab 140 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 24 | 31.7 seconds |
| Romosozumab 140 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 12 | 44.6 seconds |
| Romosozumab 140 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 16 | 39.7 seconds |
| Romosozumab 140 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 2 | 121.7 seconds |
| Romosozumab 210 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 16 | 50.1 seconds |
| Romosozumab 210 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 20 | 45.6 seconds |
| Romosozumab 210 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 52 | 36.3 seconds |
| Romosozumab 210 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 24 | 40.9 seconds |
| Romosozumab 210 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 2 | 129.8 seconds |
| Romosozumab 210 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 36 | 38.7 seconds |
| Romosozumab 210 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 12 | 56.3 seconds |
| Romosozumab 210 mg | Timed-Up-and-Go (TUG) at Each Visit | Week 6 | 86.7 seconds |
Secondary
Time to Radiographic Healing
Time to radiographic healing is the time interval from the surgery date for the eligible hip fracture to the date of radiographic healing, defined as effacement of the fracture lines by newly formed bone along the cortices and within the trabecular bone on anteroposterior and lateral (or oblique) radiographs. Radiographic fracture healing was determined by a panel of independent reviewers blinded to treatment. The cumulative incidence function (CIF) method was used to estimate the median time to radiographic healing and the confidence intervals. Unplanned revision surgery to promote healing was considered a competing risk in CIF estimate.
Time frame: 52 weeks
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Radiographic Healing | 16.4 weeks |
| Romosozumab 70 mg | Time to Radiographic Healing | 16.9 weeks |
| Romosozumab 140 mg | Time to Radiographic Healing | 16.6 weeks |
| Romosozumab 210 mg | Time to Radiographic Healing | 16.9 weeks |