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

Phase 2

Completed

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

Interventions: Drug: Placebo pill
Drug: Rosiglitazone

Registration Number: NCT00609362

Lead Sponsor: University of Aarhus

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 57

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo pill	25 women 60 to 75 years of age receiving placebo once a day for 14 weeks
Rosiglitazone	Rosiglitazone	25 women age 60 to 75 years receiving rosiglitazone 8 mg/day

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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