Change in Bone Marrow Fat Content, Change in Bone Mineral Density
Conditions
Keywords
BMD, Rosiglitazone, Bone marrow fat
Brief summary
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: 1. 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. 2. The effect on bone turnover will be measured in blood- and urine samples at the same times. 3. The effect on fat distribution will be evaluated by an MRI scan after treatment. 4. The effect on bone marrow cells will be investigated bone marrow sampling immediately after treatment 5. 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
Interventions
DRUGPlacebo pill
One encapsulated placebo pill a day for 14 weeks
DRUGRosiglitazone
one tablet of rosiglitazone 8 milligrams per day for 14 weeks
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
60 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Percent Change in Bone Mineral Density (BMD) From Baseline to 14 Weeks Between the Rosiglitazone Group and the Placebo Group | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Percent Change in Bone Marrow Fat (Given by a Lipid to Water Ratio) in the Spine. | 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 | 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 | Before and after treatment | — |
Countries
Denmark
Participant flow
Recruitment details
Recruitment commenced january 2008 and ended february 2009. Participants were recruited by ads in local papers and called our osteoporosis clinic. 179 called and after a course description 150 were sent information. After having read that 74 paid a visit to the clinic.
Pre-assignment details
74 individuals were screened. 17 were screen failures due to exclusion criteria. 57 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Rosiglitazone 25 women age 60 to 75 years receiving rosiglitazone 8 mg/day | 29 |
| Placebo 25 women 60 to 75 years of age receiving placebo once a day for 14 weeks | 28 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | Rosiglitazone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 14 Participants | 26 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 15 Participants | 31 Participants |
| Age Continuous | 65.3 years STANDARD_DEVIATION 4.3 | 65.1 years STANDARD_DEVIATION 3.5 | 65.2 years STANDARD_DEVIATION 3.8 |
| Region of Enrollment Denmark | 28 participants | 29 participants | 57 participants |
| Sex: Female, Male Female | 28 Participants | 29 Participants | 57 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 | — / — | — / — |
| other Total, other adverse events | 19 / 26 | 15 / 27 |
| serious Total, serious adverse events | 0 / 26 | 0 / 27 |
Outcome results
Primary
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)
Time frame: BMD measured at baseline and after 14 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosiglitazone | Difference in Percent Change in Bone Mineral Density (BMD) From Baseline to 14 Weeks Between the Rosiglitazone Group and the Placebo Group | -1.3 Percent change from baseline | Standard Deviation 3.1 |
| Placebo | Difference in Percent Change in Bone Mineral Density (BMD) From Baseline to 14 Weeks Between the Rosiglitazone Group and the Placebo Group | 0.3 Percent change from baseline | Standard Deviation 2.9 |
Comparison: The minimum number of participants was determined by power calculations to be 44 (22 in each group), assuming a difference in change in BMD of 1.7%, a standard deviation of 2%, a power of 80%, and a level of significance of 5%.p-value: 0.055t-test, 2 sided
Secondary
Change in Gene Expression in Bone Marrow and Fat Cells
Time frame: Before and after treatment
Secondary
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)
Time frame: Measured at baseline and after 14 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosiglitazone | Difference in Percent Change in Bone Marrow Fat (Given by a Lipid to Water Ratio) in the Spine. | -13.5 Percent change in LWR | Standard Deviation 5.5 |
| Placebo | Difference in Percent Change in Bone Marrow Fat (Given by a Lipid to Water Ratio) in the Spine. | 6.8 Percent change in LWR | Standard Deviation 24.4 |
p-value: 0.056t-test, 2 sided
Secondary
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).
Time frame: At baseline and after 14 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosiglitazone | Difference in Percent Change in Level of C-terminal Telopeptide (CTx) Between the Rosiglitazone and Placebo Groups | 20.4 Percent change from baseline | Standard Deviation 38.6 |
| Placebo | Difference in Percent Change in Level of C-terminal Telopeptide (CTx) Between the Rosiglitazone and Placebo Groups | -7.1 Percent change from baseline | Standard Deviation 24.4 |
p-value: 0.003t-test, 2 sided