Osteoporosis
Conditions
Keywords
Glucocorticoid Induced
Brief summary
The objective of this study is to test the hypothesis that teriparatide is superior to the active comparator in the change from baseline to 18 months of lumbar spine volumetric trabecular bone mineral density (BMD) in males with glucocorticoid-induced osteoporosis.
Detailed description
This study is a multinational, European, multicenter, randomized, open-label, active comparator controlled study with 2 study periods: a screening phase of up to 6 weeks, and an open-label treatment phase of 18 months. Approximately 100 adult men with osteoporosis associated with sustained glucocorticoid therapy will be enrolled into the study. Approximately one-half of the participants (at all investigational sites) will be randomized to teriparatide 20 micrograms/day (ug/day given as a subcutaneous (sc) injection), and the other half randomized to risedronate 35 milligrams (mg) once weekly (QW) oral (po) tablet. All participants will receive approximately 1000 mg/day elemental calcium and 800 to 1200 international units per day (IU/day) of vitamin D.
Interventions
DRUGTeriparatide
20 µg/day sc for 18 months
DRUGRisedronate
35 mg/week po for 18 months
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
25 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ambulatory men 25 years of age and older presenting to Visit 1 with a bone mineral density (BMD) of at least 1.5 standard deviation (SD) below the corresponding normal young adult men average BMD (T score of -1.5 or lower), as determined from the manufacturer's database at any of the following regions of interest: total hip, femoral neck, or lumbar spine * Have received glucocorticoid therapy at an average dose of at least 5.0 milligrams (mg) per day of prednisone or its equivalent for a minimum of 3 consecutive months immediately preceding screening (Visit 1), as determined by medical history. * A minimum of 2 lumbar vertebrae (L) in the L-1 through L-3 region must be evaluable by quantitative computerized tomography. * Normal or clinically insignificant abnormal laboratory values (as determined by the investigator) including serum calcium, parathyroid hormone (PTH) (1 84), and 25 hydroxyvitamin D concentrations, and alkaline phosphatase activity.
Exclusion criteria
* Presence of a mild, moderate, or severe spinal fracture in both the twelfth thoracic vertebra (T-12) and first lumbar vertebra (L-1), as determined by the central reading facility using the semiquantitative technique. * Abnormal albumin-corrected serum calcium levels * History of unresolved skeletal diseases that affect bone metabolism other than glucocorticoid-induced osteoporosis * History of malignant neoplasms in the 5 years prior to Visit 2, with the exception of superficial basal cell or squamous cell carcinomas of the skin that have been definitively treated. Increased baseline risk of osteosarcoma; this includes patients with Paget's disease of the bone, previous primary skeletal malignancy, or skeletal exposure to therapeutic irradiation. * Abnormal thyroid function not corrected by therapy * Past and/or current treatment with certain medications.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Lumbar Spine Volumetric Trabecular Bone Mineral Density (BMD) by Quantitative Computerized Tomography (QCT) at 18 Months | Baseline, 18 months | Least Squares (LS) Means were adjusted for age, baseline serum aminoterminal propeptide of Type I procollagen (P1NP), fracture less than 12 months before study start, duration of prior bisphosphonate use, screening glucocorticoid dose, and cumulative glucocorticoid dose before and during the trial. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in High Resolution Quantitative Computerized Technology (HR-QCT) of Integral and Trabecular Bone Mineral Density (BMD) of the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months | Baseline, 6 months, 18 months | Three-dimensional (3-D) microstructure variables of T12 were assessed by HR-QCT. In contrast with regular QCT that assessed 3 millimeter (mm) slide thickness, HR-QCT used segmentation of 1 single vertebra with approximately 100 consecutive slides reconstructed at 300-400 micrometer (µm) slice increments covering the complete vertebral body. Least Squares (LS) Means were adjusted for age, baseline P1NP, fracture less than 12 months before study start, duration of prior bisphosphonate use, screening glucocorticoid dose, and cumulative glucocorticoid dose before and during the trial. |
| Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Baseline, 6 months, 18 months | Anterior bending and axial torsion were measured using HR-QCT-based finite element analysis to determine stiffness and strength of T12. Stiffness evaluated strength of the vertebral body, defined as the slope of the initial step of the force-displacement curve. Strength of the vertebral body was evaluated under compressive loading conditions using computer simulation. LS Means were adjusted for age, baseline P1NP, fracture less than 12 months before study start, duration of prior bisphosphonate use, screening glucocorticoid dose, and cumulative glucocorticoid dose before and during the trial. |
| Change From Baseline in Axial Compression by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Baseline, 6 months, 18 months | Axial compression was measured using HR-QCT-based finite element analysis to determine stiffness and strength of T12. Stiffness evaluated the strength of the vertebral body, defined as the slope of the initial step of the force-displacement curve. Strength of the vertebral body was evaluated under compressive loading conditions using computer simulation. LS Means were adjusted for age, baseline P1NP, fracture less than 12 months before study start, duration of prior bisphosphonate use, screening glucocorticoid dose, and cumulative glucocorticoid dose before and during the trial. |
| Change From Baseline in Lumbar Spine Volumetric Trabecular Bone Mineral Density (BMD) by Quantitative Computerized Technology (QCT) at 6 Months | Baseline, 6 months | Least Squares (LS) Means were adjusted for age, baseline propeptide of Type I procollagen (P1NP), fracture less than 12 months before study start, duration of prior bisphosphonate use, screening glucocorticoid dose, and cumulative glucocorticoid dose before and during the trial. |
| Change From Baseline in Serum Aminoterminal Propeptide of Type I Procollagen (P1NP) at 3 Months, 6 Months, and 18 Months | Baseline, 3 months, 6 months, 18 months | P1NP was used as a serum biochemical marker of collagen synthesis, reflecting the formation of new osteoid. |
| Change From Baseline in Serum Type I Collagen Degradation Fragments (β-CTx) at 3 Months, 6 Months, and 18 Months | 3, 6, 18 months | β-CTx was used as a biochemical marker of bone turnover/resorption, reflecting collagen breakdown of the bone matrix. |
| Number of Participants With Adverse Events (AEs) | Baseline up to 18 months | Summary tables of serious AEs (SAEs) and all other non-serious AEs are located in the Reported Adverse Event Module. Fractures that occurred during the study were collected separately as an additional safety variable. The number of participants experiencing hypercalcemia was summarized for each treatment arm. Hypercalcemia was defined as a serum calcium level corrected for albumin of \>2.7 millimole per liter (mmol/L) (10.8 milligram per deciliter \[mg/dL\]). |
| Change From Baseline in Areal Bone Mineral Density (BMD) at Lumbar Spine, Femoral Neck, and Total Hip at 18 Months | Baseline, 18 months | Dual x-ray absorptiometry (DXA) techniques validated this measurement at skeletal sites that are at risk of osteoporotic fracture, such as lumbar spine, femoral neck, and hip. |
Countries
Germany, Greece, Italy, Spain
Participant flow
Pre-assignment details
Of the 174 participants who were enrolled into the study, 92 were eligible and randomly assigned to the treatment arms.
Participants by arm
| Arm | Count |
|---|---|
| Teriparatide Teriparatide 20 microgram (µg) subcutaneous (sc) injection once daily (QD) | 45 |
| Risedronate Risedronate 35 milligrams (mg) oral (po) tablet once weekly (QW) | 47 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | Risedronate | Total | Teriparatide |
|---|---|---|---|
| Age Continuous | 55.1 years STANDARD_DEVIATION 15.54 | 56.3 years STANDARD_DEVIATION 14.24 | 57.5 years STANDARD_DEVIATION 12.8 |
| Number of participants with fractures before study With fractures | 17 participants | 36 participants | 19 participants |
| Number of participants with fractures before study Without fractures | 30 participants | 56 participants | 26 participants |
| Race/Ethnicity, Customized Caucasian | 46 participants | 90 participants | 44 participants |
| Race/Ethnicity, Customized East Asian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Germany | 21 participants | 40 participants | 19 participants |
| Region of Enrollment Greece | 6 participants | 12 participants | 6 participants |
| Region of Enrollment Italy | 8 participants | 13 participants | 5 participants |
| Region of Enrollment Spain | 12 participants | 27 participants | 15 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 47 Participants | 92 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 45 | 30 / 47 |
| serious Total, serious adverse events | 13 / 45 | 22 / 47 |
Outcome results
Primary
Change From Baseline in Lumbar Spine Volumetric Trabecular Bone Mineral Density (BMD) by Quantitative Computerized Tomography (QCT) at 18 Months
Least Squares (LS) Means were adjusted for age, baseline serum aminoterminal propeptide of Type I procollagen (P1NP), fracture less than 12 months before study start, duration of prior bisphosphonate use, screening glucocorticoid dose, and cumulative glucocorticoid dose before and during the trial.
Time frame: Baseline, 18 months
Population: The analysis population was the primary efficacy population, which included all randomized participants who received at least 1 dose of study medication (full analysis set) and had a lumbar spine volumetric trabecular BMD measurement at baseline and at ≥1 post-baseline visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Teriparatide | Change From Baseline in Lumbar Spine Volumetric Trabecular Bone Mineral Density (BMD) by Quantitative Computerized Tomography (QCT) at 18 Months | 12.28 milligram per cubic centimeter (mg/cm^3) | Standard Error 3.16 |
| Risedronate | Change From Baseline in Lumbar Spine Volumetric Trabecular Bone Mineral Density (BMD) by Quantitative Computerized Tomography (QCT) at 18 Months | 2.94 milligram per cubic centimeter (mg/cm^3) | Standard Error 3.14 |
Secondary
Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength
Anterior bending and axial torsion were measured using HR-QCT-based finite element analysis to determine stiffness and strength of T12. Stiffness evaluated strength of the vertebral body, defined as the slope of the initial step of the force-displacement curve. Strength of the vertebral body was evaluated under compressive loading conditions using computer simulation. LS Means were adjusted for age, baseline P1NP, fracture less than 12 months before study start, duration of prior bisphosphonate use, screening glucocorticoid dose, and cumulative glucocorticoid dose before and during the trial.
Time frame: Baseline, 6 months, 18 months
Population: The analysis population was the full analysis set (FAS), which included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Anterior bending stiffness at 6 months | 664969.0 Newton/millimeter/radian (N/mm/rad) | Standard Error 317684 |
| Teriparatide | Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Anterior bending stiffness at 18 months | 1209225.0 Newton/millimeter/radian (N/mm/rad) | Standard Error 300977 |
| Teriparatide | Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Axial torsion stiffness at 6 months | 142902.9 Newton/millimeter/radian (N/mm/rad) | Standard Error 71714.2 |
| Teriparatide | Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Axial torsion stiffness at 18 months | 279392.8 Newton/millimeter/radian (N/mm/rad) | Standard Error 68284.5 |
| Teriparatide | Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Anterior bending strength at 6 months | 12490.9 Newton/millimeter/radian (N/mm/rad) | Standard Error 8405 |
| Teriparatide | Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Anterior bending strength at 18 months | 26046.4 Newton/millimeter/radian (N/mm/rad) | Standard Error 8304.1 |
| Teriparatide | Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Axial torsion strength at 6 months | 6127.7 Newton/millimeter/radian (N/mm/rad) | Standard Error 4132.3 |
| Teriparatide | Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Axial torsion strength at 18 months | 14181.3 Newton/millimeter/radian (N/mm/rad) | Standard Error 3954.4 |
| Risedronate | Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Axial torsion strength at 18 months | 2545.8 Newton/millimeter/radian (N/mm/rad) | Standard Error 4228.7 |
| Risedronate | Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Anterior bending stiffness at 6 months | 415705.0 Newton/millimeter/radian (N/mm/rad) | Standard Error 323135 |
| Risedronate | Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Anterior bending strength at 6 months | 8827.2 Newton/millimeter/radian (N/mm/rad) | Standard Error 8741 |
| Risedronate | Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Anterior bending stiffness at 18 months | 233283.0 Newton/millimeter/radian (N/mm/rad) | Standard Error 322829 |
| Risedronate | Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Axial torsion strength at 6 months | 3664.0 Newton/millimeter/radian (N/mm/rad) | Standard Error 4233.5 |
| Risedronate | Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Axial torsion stiffness at 6 months | 77830.7 Newton/millimeter/radian (N/mm/rad) | Standard Error 72947.9 |
| Risedronate | Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Anterior bending strength at 18 months | 4822.0 Newton/millimeter/radian (N/mm/rad) | Standard Error 8686.6 |
| Risedronate | Change From Baseline in Anterior Bending and Axial Torsion by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Axial torsion stiffness at 18 months | 56639.3 Newton/millimeter/radian (N/mm/rad) | Standard Error 72946.9 |
Secondary
Change From Baseline in Areal Bone Mineral Density (BMD) at Lumbar Spine, Femoral Neck, and Total Hip at 18 Months
Dual x-ray absorptiometry (DXA) techniques validated this measurement at skeletal sites that are at risk of osteoporotic fracture, such as lumbar spine, femoral neck, and hip.
Time frame: Baseline, 18 months
Population: The analysis population was the full analysis set (FAS), which included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Change From Baseline in Areal Bone Mineral Density (BMD) at Lumbar Spine, Femoral Neck, and Total Hip at 18 Months | Lumbar spine (n=38; n=39) | 0.068 grams per square centimeter (g/cm^2) | Standard Deviation 0.0685 |
| Teriparatide | Change From Baseline in Areal Bone Mineral Density (BMD) at Lumbar Spine, Femoral Neck, and Total Hip at 18 Months | Hip (n=38; n=37) | 0.014 grams per square centimeter (g/cm^2) | Standard Deviation 0.0319 |
| Teriparatide | Change From Baseline in Areal Bone Mineral Density (BMD) at Lumbar Spine, Femoral Neck, and Total Hip at 18 Months | Femoral neck (n=38; n=37) | 0.014 grams per square centimeter (g/cm^2) | Standard Deviation 0.0446 |
| Risedronate | Change From Baseline in Areal Bone Mineral Density (BMD) at Lumbar Spine, Femoral Neck, and Total Hip at 18 Months | Lumbar spine (n=38; n=39) | 0.037 grams per square centimeter (g/cm^2) | Standard Deviation 0.0493 |
| Risedronate | Change From Baseline in Areal Bone Mineral Density (BMD) at Lumbar Spine, Femoral Neck, and Total Hip at 18 Months | Hip (n=38; n=37) | 0.007 grams per square centimeter (g/cm^2) | Standard Deviation 0.032 |
| Risedronate | Change From Baseline in Areal Bone Mineral Density (BMD) at Lumbar Spine, Femoral Neck, and Total Hip at 18 Months | Femoral neck (n=38; n=37) | -0.007 grams per square centimeter (g/cm^2) | Standard Deviation 0.0333 |
Secondary
Change From Baseline in Axial Compression by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength
Axial compression was measured using HR-QCT-based finite element analysis to determine stiffness and strength of T12. Stiffness evaluated the strength of the vertebral body, defined as the slope of the initial step of the force-displacement curve. Strength of the vertebral body was evaluated under compressive loading conditions using computer simulation. LS Means were adjusted for age, baseline P1NP, fracture less than 12 months before study start, duration of prior bisphosphonate use, screening glucocorticoid dose, and cumulative glucocorticoid dose before and during the trial.
Time frame: Baseline, 6 months, 18 months
Population: The analysis population was the full analysis set (FAS), which included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Change From Baseline in Axial Compression by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Axial compression stiffness at 6 months | 890.7 Newton per millimeter (N/mm) | Standard Error 596.6 |
| Teriparatide | Change From Baseline in Axial Compression by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Axial compression stiffness at 18 months | 1973.9 Newton per millimeter (N/mm) | Standard Error 569 |
| Teriparatide | Change From Baseline in Axial Compression by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Axial compression strength at 6 months | 580.7 Newton per millimeter (N/mm) | Standard Error 444.6 |
| Teriparatide | Change From Baseline in Axial Compression by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Axial compression strength at 18 months | 1287.5 Newton per millimeter (N/mm) | Standard Error 424 |
| Risedronate | Change From Baseline in Axial Compression by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Axial compression strength at 18 months | 209.4 Newton per millimeter (N/mm) | Standard Error 455.5 |
| Risedronate | Change From Baseline in Axial Compression by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Axial compression stiffness at 6 months | 407.6 Newton per millimeter (N/mm) | Standard Error 607.6 |
| Risedronate | Change From Baseline in Axial Compression by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Axial compression strength at 6 months | 313.6 Newton per millimeter (N/mm) | Standard Error 457 |
| Risedronate | Change From Baseline in Axial Compression by Finite Element Analysis in the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months: Stiffness and Strength | Axial compression stiffness at 18 months | 363.7 Newton per millimeter (N/mm) | Standard Error 605.9 |
Secondary
Change From Baseline in High Resolution Quantitative Computerized Technology (HR-QCT) of Integral and Trabecular Bone Mineral Density (BMD) of the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months
Three-dimensional (3-D) microstructure variables of T12 were assessed by HR-QCT. In contrast with regular QCT that assessed 3 millimeter (mm) slide thickness, HR-QCT used segmentation of 1 single vertebra with approximately 100 consecutive slides reconstructed at 300-400 micrometer (µm) slice increments covering the complete vertebral body. Least Squares (LS) Means were adjusted for age, baseline P1NP, fracture less than 12 months before study start, duration of prior bisphosphonate use, screening glucocorticoid dose, and cumulative glucocorticoid dose before and during the trial.
Time frame: Baseline, 6 months, 18 months
Population: The analysis population was the full analysis set (FAS), which included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Change From Baseline in High Resolution Quantitative Computerized Technology (HR-QCT) of Integral and Trabecular Bone Mineral Density (BMD) of the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months | Integral BMD at 6 months | -0.42 milligram per cubic centimeter (mg/cm^3) | Standard Error 6.42 |
| Teriparatide | Change From Baseline in High Resolution Quantitative Computerized Technology (HR-QCT) of Integral and Trabecular Bone Mineral Density (BMD) of the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months | Integral BMD at 18 months | 10.72 milligram per cubic centimeter (mg/cm^3) | Standard Error 6.22 |
| Teriparatide | Change From Baseline in High Resolution Quantitative Computerized Technology (HR-QCT) of Integral and Trabecular Bone Mineral Density (BMD) of the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months | Trabecular BMD at 6 months | -0.70 milligram per cubic centimeter (mg/cm^3) | Standard Error 5.26 |
| Teriparatide | Change From Baseline in High Resolution Quantitative Computerized Technology (HR-QCT) of Integral and Trabecular Bone Mineral Density (BMD) of the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months | Trabecular BMD at 18 months | 9.53 milligram per cubic centimeter (mg/cm^3) | Standard Error 5.09 |
| Risedronate | Change From Baseline in High Resolution Quantitative Computerized Technology (HR-QCT) of Integral and Trabecular Bone Mineral Density (BMD) of the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months | Trabecular BMD at 18 months | 0.22 milligram per cubic centimeter (mg/cm^3) | Standard Error 5.82 |
| Risedronate | Change From Baseline in High Resolution Quantitative Computerized Technology (HR-QCT) of Integral and Trabecular Bone Mineral Density (BMD) of the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months | Integral BMD at 6 months | -1.91 milligram per cubic centimeter (mg/cm^3) | Standard Error 7.11 |
| Risedronate | Change From Baseline in High Resolution Quantitative Computerized Technology (HR-QCT) of Integral and Trabecular Bone Mineral Density (BMD) of the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months | Trabecular BMD at 6 months | -0.87 milligram per cubic centimeter (mg/cm^3) | Standard Error 5.85 |
| Risedronate | Change From Baseline in High Resolution Quantitative Computerized Technology (HR-QCT) of Integral and Trabecular Bone Mineral Density (BMD) of the 12th Thoracic Vertebra (T12) at 6 Months and 18 Months | Integral BMD at 18 months | 0.68 milligram per cubic centimeter (mg/cm^3) | Standard Error 7.08 |
Secondary
Change From Baseline in Lumbar Spine Volumetric Trabecular Bone Mineral Density (BMD) by Quantitative Computerized Technology (QCT) at 6 Months
Least Squares (LS) Means were adjusted for age, baseline propeptide of Type I procollagen (P1NP), fracture less than 12 months before study start, duration of prior bisphosphonate use, screening glucocorticoid dose, and cumulative glucocorticoid dose before and during the trial.
Time frame: Baseline, 6 months
Population: The analysis population was the primary efficacy population, which included all randomized participants who received at least 1 dose of study medication (full analysis set) and had a lumbar spine volumetric trabecular BMD measurement at baseline and at ≥1 post-baseline visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Teriparatide | Change From Baseline in Lumbar Spine Volumetric Trabecular Bone Mineral Density (BMD) by Quantitative Computerized Technology (QCT) at 6 Months | 4.31 milligram per cubic centimeter (mg/cm^3) | Standard Error 3.15 |
| Risedronate | Change From Baseline in Lumbar Spine Volumetric Trabecular Bone Mineral Density (BMD) by Quantitative Computerized Technology (QCT) at 6 Months | 2.52 milligram per cubic centimeter (mg/cm^3) | Standard Error 3.16 |
Secondary
Change From Baseline in Serum Aminoterminal Propeptide of Type I Procollagen (P1NP) at 3 Months, 6 Months, and 18 Months
P1NP was used as a serum biochemical marker of collagen synthesis, reflecting the formation of new osteoid.
Time frame: Baseline, 3 months, 6 months, 18 months
Population: The analysis population was the full analysis set (FAS), which included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Change From Baseline in Serum Aminoterminal Propeptide of Type I Procollagen (P1NP) at 3 Months, 6 Months, and 18 Months | P1NP at 3 months | 27.33 micrograms per deciliter (μg/dL) | Standard Error 8.32 |
| Teriparatide | Change From Baseline in Serum Aminoterminal Propeptide of Type I Procollagen (P1NP) at 3 Months, 6 Months, and 18 Months | P1NP at 6 months | 52.55 micrograms per deciliter (μg/dL) | Standard Error 8.27 |
| Teriparatide | Change From Baseline in Serum Aminoterminal Propeptide of Type I Procollagen (P1NP) at 3 Months, 6 Months, and 18 Months | P1NP at 18 months | 28.48 micrograms per deciliter (μg/dL) | Standard Error 8.74 |
| Risedronate | Change From Baseline in Serum Aminoterminal Propeptide of Type I Procollagen (P1NP) at 3 Months, 6 Months, and 18 Months | P1NP at 3 months | -16.09 micrograms per deciliter (μg/dL) | Standard Error 7.82 |
| Risedronate | Change From Baseline in Serum Aminoterminal Propeptide of Type I Procollagen (P1NP) at 3 Months, 6 Months, and 18 Months | P1NP at 6 months | -16.50 micrograms per deciliter (μg/dL) | Standard Error 7.95 |
| Risedronate | Change From Baseline in Serum Aminoterminal Propeptide of Type I Procollagen (P1NP) at 3 Months, 6 Months, and 18 Months | P1NP at 18 months | -15.58 micrograms per deciliter (μg/dL) | Standard Error 8.58 |
Secondary
Change From Baseline in Serum Type I Collagen Degradation Fragments (β-CTx) at 3 Months, 6 Months, and 18 Months
β-CTx was used as a biochemical marker of bone turnover/resorption, reflecting collagen breakdown of the bone matrix.
Time frame: 3, 6, 18 months
Population: The analysis population was the full analysis set (FAS), which included all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Teriparatide | Change From Baseline in Serum Type I Collagen Degradation Fragments (β-CTx) at 3 Months, 6 Months, and 18 Months | β-CTx at 3 months | 0.12 nanograms per deciliter (ng/dL) | Standard Error 0.07 |
| Teriparatide | Change From Baseline in Serum Type I Collagen Degradation Fragments (β-CTx) at 3 Months, 6 Months, and 18 Months | β-CTx at 6 months | 0.25 nanograms per deciliter (ng/dL) | Standard Error 0.07 |
| Teriparatide | Change From Baseline in Serum Type I Collagen Degradation Fragments (β-CTx) at 3 Months, 6 Months, and 18 Months | β-CTx at 18 months | 0.03 nanograms per deciliter (ng/dL) | Standard Error 0.08 |
| Risedronate | Change From Baseline in Serum Type I Collagen Degradation Fragments (β-CTx) at 3 Months, 6 Months, and 18 Months | β-CTx at 3 months | -0.15 nanograms per deciliter (ng/dL) | Standard Error 0.07 |
| Risedronate | Change From Baseline in Serum Type I Collagen Degradation Fragments (β-CTx) at 3 Months, 6 Months, and 18 Months | β-CTx at 6 months | -0.14 nanograms per deciliter (ng/dL) | Standard Error 0.07 |
| Risedronate | Change From Baseline in Serum Type I Collagen Degradation Fragments (β-CTx) at 3 Months, 6 Months, and 18 Months | β-CTx at 18 months | -0.11 nanograms per deciliter (ng/dL) | Standard Error 0.07 |
Secondary
Number of Participants With Adverse Events (AEs)
Summary tables of serious AEs (SAEs) and all other non-serious AEs are located in the Reported Adverse Event Module. Fractures that occurred during the study were collected separately as an additional safety variable. The number of participants experiencing hypercalcemia was summarized for each treatment arm. Hypercalcemia was defined as a serum calcium level corrected for albumin of \>2.7 millimole per liter (mmol/L) (10.8 milligram per deciliter \[mg/dL\]).
Time frame: Baseline up to 18 months
Population: The safety analysis set included all participants who received study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Teriparatide | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 13 participants |
| Teriparatide | Number of Participants With Adverse Events (AEs) | Other Non-serious AEs | 22 participants |
| Teriparatide | Number of Participants With Adverse Events (AEs) | Fractures | 0 participants |
| Teriparatide | Number of Participants With Adverse Events (AEs) | Hypercalcemia | 0 participants |
| Risedronate | Number of Participants With Adverse Events (AEs) | Hypercalcemia | 0 participants |
| Risedronate | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 22 participants |
| Risedronate | Number of Participants With Adverse Events (AEs) | Fractures | 5 participants |
| Risedronate | Number of Participants With Adverse Events (AEs) | Other Non-serious AEs | 30 participants |