µMRI of Therapeutic Intervention in Postmenopausal Osteoporosis

Study Overview
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Brief Summary
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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
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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.

Official Title
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NMR Imaging and Stereological Analysis of Trabecular Bone in Female Subjects 60 and Older at Risk of Fracture Receiving Either Zoledronic Acid or Teriparatide

Conditions
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Osteoporosis, Osteopenia

Intervention / Treatment
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* Other: Virtual Bone Biopsy
* Drug: Teriparatide
* Drug: Zoledronic Acid


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Postmenopausal women, ages ≥ 60 years, indicated for treatment with antiresorptive or anabolic drugs due to severe osteoporosis and high risk of fracture.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Teriparatide (Forteo)<br>20 µg of Teriparatide will be self-injected subcutaneously once a day for 12 months and an MRI at 3T ('Virtual Bone Biopsy') will be performed at 0 and 12 months. | Other: Virtual Bone Biopsy<br>* 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.<br>* Other names: VBB;Drug: Teriparatide<br>* Participants are clinically indicated for treatment.<br>* Other names: Forteo;|
| Active Comparator: Zoledronic Acid (Reclast)<br>5 mg of zoledronic Acid will be administered intravenously at baseline and 12 months and an MRI at 3T ('Virtual Bone Biopsy) will be performed at 0 and 12 months. | Other: Virtual Bone Biopsy<br>* 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.<br>* Other names: VBB;Drug: Zoledronic Acid<br>* Participants are clinically indicated for treatment.<br>* Other names: Reclast;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Change in Trabecular Surface-to-curve Ratio | Ratio of the volume densities of surface (S) and curve (C)-type voxels, S/C | Change between baseline and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Change in Bone Volume Fraction (BVF) | Average fractional content of bone expressed in percent | Change between baseline and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoporosis, Osteopenia, Fracture Risk, teriparatide or Forteo, zoledronic acid or Reclast