Clinical trial NCT00609362: The Effect of Glitazone Treatment on Bone Marrow and Bone Marrow Cells
Official title: The Effect of Glitazone Treatment on Bone Marrow and Bone Marrow Cells
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Change in Bone Mineral Density
Change in Bone Marrow Fat Content
Keywords: BMD
Rosiglitazone
Bone marrow fat
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2008-02-07
Enrollment: 57
Sex: FEMALE
Minimum age (years): 60
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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


Eligibility criteria: 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

Primary outcomes:
measure: Difference in Percent Change in Bone Mineral Density (BMD) From Baseline to 14 Weeks Between the Rosiglitazone Group and the Placebo Group
timeFrame: BMD measured at baseline and after 14 weeks of treatment
Secondary outcomes:
measure: Difference in Percent Change in Bone Marrow Fat (Given by a Lipid to Water Ratio) in the Spine.
timeFrame: Measured at baseline and after 14 weeks of treatment
measure: Difference in Percent Change in Level of C-terminal Telopeptide (CTx) Between the Rosiglitazone and Placebo Groups
timeFrame: At baseline and after 14 weeks of treatment
measure: Change in Gene Expression in Bone Marrow and Fat Cells
timeFrame: Before and after treatment
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
Study officials:
affiliation: Aarhus University Hospital
name: Torben Harsløf, Dr.
role: PRINCIPAL_INVESTIGATOR
References: