The Effect of Glitazone Treatment on Bone Marrow and Bone Marrow Cells

Study Overview
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Brief Summary
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Osteoporosis is a generalised bone disease leading to an increased risk of fractures. The disease is caused partly by environmental and partly by genetic factors. It is well known that the fat content of the bone marrow is increased in osteoporotic patients. Animal studies suggest that stimulation of bone marrow stem cells through the molecule PPARgamma with the drug rosiglitazone converts the stem cells to fat cells instead of bone cells thereby decreasing bone strength. In a single study healthy volunteers were treated with rosiglitazone for 14 weeks and had a decrease in bone mineral density. In the present study we wish to investigate the effect of this treatment on bone and fat tissue. 25 women above the age of 60 will be treated with rosiglitazone 8 mg/day for 14 weeks and compared with 25 women receiving placebo. The effect will be evaluated as follows: The effect on bone marrow density will be examined by a bone scan prior to and after treatment and again after 6 and 9 months. The effect on bone turnover will be measured in blood- and urine samples at the same times. The effect on fat distribution will be evaluated by an MRI scan after treatment. The effect on bone marrow cells will be investigated bone marrow sampling immediately after treatment The direct effect on fat will be examined by a biopsy immediately after treatment The study hypothesis is that rosiglitazone treatment decreases bone mineral density and increases bone marrow fat content. The causal molecular mechanisms will be investigated from the bone marrow and fat samples

Official Title
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The Effect of Glitazone Treatment on Bone Marrow and Bone Marrow Cells

Conditions
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Change in Bone Mineral Density, Change in Bone Marrow Fat Content

Intervention / Treatment
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* Drug: Rosiglitazone
* Drug: Placebo pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women age 60-75 with no rosiglitazone allergy Exclusion Criteria: Osteoporosis Diabetes Hyperthyroidism, untreated hypothyroidism, hyperparathyroidism Treatment with bone active drugs Low impact fracture Heart disease Kidney failure Liver failure Anaemia Ineligibility for MRI-scan Cancer within last 5 years

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rosiglitazone<br>25 women age 60 to 75 years receiving rosiglitazone 8 mg/day | Drug: Rosiglitazone<br>* one tablet of rosiglitazone 8 milligrams per day for 14 weeks<br>* Other names: Avandia;|
| Placebo Comparator: Placebo<br>25 women 60 to 75 years of age receiving placebo once a day for 14 weeks | Drug: Placebo pill<br>* One encapsulated placebo pill a day for 14 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Percent Change in Bone Mineral Density (BMD) From Baseline to 14 Weeks Between the Rosiglitazone Group and the Placebo Group | Difference in percent change in bone mineral density (BMD) from baseline to 14 weeks between the rosiglitazone group and the placebo group. BMD was assesed using dual x-ray absorptiometry (DXA) | BMD measured at baseline and after 14 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Percent Change in Bone Marrow Fat (Given by a Lipid to Water Ratio) in the Spine. | Bone marrow fat was measured using MRI spectroscopy providing a measure of bone marrow fat as a ratio to bone marrow water, the lipid-water ratio (LWR) | Measured at baseline and after 14 weeks of treatment | 
| Difference in Percent Change in Level of C-terminal Telopeptide (CTx) Between the Rosiglitazone and Placebo Groups | C-terminal telopeptide is a marker of bone resorption. Its levels are measure in plasma using a chemiluminometric method (ECLIA). | At baseline and after 14 weeks of treatment | 
| Change in Gene Expression in Bone Marrow and Fat Cells |  | Before and after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BMD, Rosiglitazone, Bone marrow fat