The Effect of Glitazone Treatment on Bone Marrow and Bone Marrow Cells
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
|Change in Bone Mineral Density Change in Bone Marrow Fat Content||Drug: Rosiglitazone Drug: Placebo pill||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Basic Science
|Official Title:||The Effect of Glitazone Treatment on Bone Marrow and Bone Marrow Cells|
- Difference in Percent Change in Bone Mineral Density (BMD) From Baseline to 14 Weeks Between the Rosiglitazone Group and the Placebo Group [ Time Frame: BMD measured at baseline and after 14 weeks of treatment ]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)
- Difference in Percent Change in Bone Marrow Fat (Given by a Lipid to Water Ratio) in the Spine. [ Time Frame: Measured at baseline and after 14 weeks of treatment ]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)
- Difference in Percent Change in Level of C-terminal Telopeptide (CTx) Between the Rosiglitazone and Placebo Groups [ Time Frame: At baseline and after 14 weeks of treatment ]C-terminal telopeptide is a marker of bone resorption. Its levels are measure in plasma using a chemiluminometric method (ECLIA).
- Change in Gene Expression in Bone Marrow and Fat Cells [ Time Frame: Before and after treatment ]
|Study Start Date:||January 2008|
|Study Completion Date:||November 2009|
|Primary Completion Date:||November 2009 (Final data collection date for primary outcome measure)|
Active Comparator: Rosiglitazone
25 women age 60 to 75 years receiving rosiglitazone 8 mg/day
one tablet of rosiglitazone 8 milligrams per day for 14 weeks
Other Name: Avandia
Placebo Comparator: Placebo
25 women 60 to 75 years of age receiving placebo once a day for 14 weeks
Drug: Placebo pill
One encapsulated placebo pill a day for 14 weeks
Please refer to this study by its ClinicalTrials.gov identifier: NCT00609362
|Aarhus University Hospital|
|Aarhus, Denmark, 8000 C|
|Principal Investigator:||Torben Harsløf, Dr.||Aarhus University Hospital|