Osteoporosis, Osteopenia
Conditions
Keywords
Osteoporosis, Osteopenia, Fracture Risk, teriparatide or Forteo, zoledronic acid or Reclast
Brief summary
The purpose of this study is to apply a novel advanced magnetic resonance imaging methodology to evaluate the response to drug intervention involving two treatment arms of postmenopausal participants with osteoporosis, randomized into either a teriparatide (Forteo™) or zoledronic acid (Reclast™) group.
Detailed description
The overall design is to determine and compare the effect of teriparatide and of zoledronic acid on trabecular architecture by magnetic resonance imaging of the midshaft tibia. Post-menopausal women, aged 60 or older with osteoporosis and/or at increased risk of fracture, will be randomized to receive either teriparatide or zoledronic acid. Trabecular microarchitecture, biomechanical parameters and bone mineral density will be examined at 0 and 12 months at 3T MRI.
Interventions
OTHERVirtual Bone Biopsy
MRI technology allowing generation of 3D images with considerably smaller voxel size than previous technology through the use of novel pulse sequences and advanced interpolation techniques.
DRUGTeriparatide
Participants are clinically indicated for treatment.
DRUGZoledronic Acid
Participants are clinically indicated for treatment.
Sponsors
Eli Lilly and Company
Novartis Pharmaceuticals
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Postmenopausal women, ages ≥ 60 years, indicated for treatment with antiresorptive or anabolic drugs due to severe osteoporosis and high risk of fracture.
Eligibility
Sex/Gender
FEMALE
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women * Age ≥ 60 years * Bone mineral density T-score of either the spine (L1-L4), total hip or femoral neck of ≤ - 2.0, or has a history of an osteoporotic fracture
Exclusion criteria
* Previous treatment with pamidronate, ibandronate, of more than 2 doses in 2 years and of zoledronic acid at any time * Previous treatment with teriparatide, alendronate or risedronate of more than 2 months in the last 24 months * Previous treatment with calcitonin within the previous year; previous treatment with an estrogen or selective estrogen modulator will not exclude a potential subject unless she has been taking it for \< 1 year (a woman who discontinued estrogen or a selective estrogen receptor within the previous year will also be excluded) * Other diseases known to affect bone, such as Paget's disease, Cushing's disease, hyperthyroidism, hyperparathyroidism, bone cancer and metastases to bone, and vitamin D deficiency * Medications known to affect bone, such as anticonvulsants, high dose glucocorticoids (20 mg/day or more \> 2 weeks within the previous 6 months) * Current alcohol use \> 3 drinks/day * Untreated or unstable cardiac, pulmonary, liver (SGOT \> 2X upper limit of normal) or renal disease (creatinine \> 1.2 mg/dL) or uncontrolled diabetes (hemoglobin A1C \> 8.0) * Prior radiation therapy to the skeleton * Cardiac pacemakers, ferromagnetic implants or brain aneurysm clips * Claustrophobia * Subjects whose initial MRI is of poor quality due to motion artifact will be asked to repeat the examination; if a repeat MRI is of poor quality due to motion artifact, the subject will be excluded from the study * Abnormalities of the which delay esophageal emptying such as stricture or achalasia * Inability to stand or sit upright for at least 30 minutes * Hypocalcemia * Uric acid level \>7.5ml/dl * Subjects with metallic objects in their bodies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Change in Trabecular Surface-to-curve Ratio | Change between baseline and 12 months | Ratio of the volume densities of surface (S) and curve (C)-type voxels, S/C |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Change in Bone Volume Fraction (BVF) | Change between baseline and 12 months | Average fractional content of bone expressed in percent |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the Philadelphia region via various modes of public advertisements (radio, newspapers, flyers).
Pre-assignment details
To qualify for participation participants must have BMD T-scores of either the spine (L1-L4) or total hip of ≤ -2.5 or a history of osteoporotic fracture.
Participants by arm
| Arm | Count |
|---|---|
| Teriparatide (Forteo) 20 µg of Teriparatide will be self-injected subcutaneously once a day for 24 months and an MRI ('Virtual Bone Biopsy') will be performed at 0 and 24 months.
Virtual Bone Biopsy by Magnetic Resonance Imaging: The MRI involves virtual bone biopsy technology currently being developed. This new technology is not commercially or elsewhere available. It allows generation of 3D images of considerably smaller voxel size than the previous technology by employing new pulse sequences and advanced interpolation techniques. The enhanced resolution will enable capturing subtle remodeling-induced changes, such as reversal of the fenestration caused by prior osteoclastic resorption cavities. It will also permit measurement of trabecular thickness with increased accuracy and precision. Advances have also been made toward superior registration of follow-up scans relative to the baseline scans. This, we project, provides improved reproducibility and thus increased statistical power. | 16 |
| Zoledronic Acid (Reclast) 5 mg of zoledronic Acid will be administered intravenously at baseline and 12 months and an MRI ('Virtual Bone Biopsy) will be performed at 0 and 24 months.
Virtual Bone Biopsy by Magnetic Resonance Imaging: The MRI involves virtual bone biopsy technology currently being developed. This new technology is not commercially or elsewhere available. It allows generation of 3D images of considerably smaller voxel size than the previous technology by employing new pulse sequences and advanced interpolation techniques. The enhanced resolution will enable capturing subtle remodeling-induced changes, such as reversal of the fenestration caused by prior osteoclastic resorption cavities. It will also permit measurement of trabecular thickness with increased accuracy and precision. Advances have also been made toward superior registration of follow-up scans relative to the baseline scans. This, we project, provides improved reproducibility and thus increased statistical power. | 17 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Zoledronic Acid (Reclast) | Total | Teriparatide (Forteo) |
|---|---|---|---|
| Age, Continuous | 66.22 years | 67.94 years | 69.55 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 33 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 9 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 24 Participants | 12 Participants |
| Sex: Female, Male Female | 17 Participants | 33 Participants | 16 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 17 |
| other Total, other adverse events | 15 / 16 | 12 / 17 |
| serious Total, serious adverse events | 1 / 16 | 0 / 17 |
Outcome results
Primary
Percentage of Change in Trabecular Surface-to-curve Ratio
Ratio of the volume densities of surface (S) and curve (C)-type voxels, S/C
Time frame: Change between baseline and 12 months
Population: Mean change in structural and mechanical markers of bone turnover between the two groups.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriparatide (Forteo) | Percentage of Change in Trabecular Surface-to-curve Ratio | 9.1 Percentage of Change | Standard Deviation 2 |
| Zoledronic Acid (Reclast) | Percentage of Change in Trabecular Surface-to-curve Ratio | 7.1 Percentage of Change | Standard Deviation 2.6 |
Secondary
Percentage of Change in Bone Volume Fraction (BVF)
Average fractional content of bone expressed in percent
Time frame: Change between baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriparatide (Forteo) | Percentage of Change in Bone Volume Fraction (BVF) | 1.0 Percentage of Change | Standard Deviation 0.8 |
| Zoledronic Acid (Reclast) | Percentage of Change in Bone Volume Fraction (BVF) | 0.6 Percentage of Change | Standard Deviation 0.3 |
Comparison: paired t-test for change from baseline to 24 monthsp-value: >0.05t-test, 2 sided