Official Title: “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:

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

Study Type: Interventional

Study Design: Basic Science, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Pharmacodynamics Study

Study Primary Completion Date: January 2010

Intervention(s) in this Clinical Trial

• Drug: Rosiglitazone
  • one tablet of rosiglitazone 8 milligrams per day for 14 weeks
• Drug: Placebo pill
  • One encapsulated placebo pill a day for 14 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Rosiglitazone
  • 25 women age 60 to 75 years receiving rosiglitazone 8 mg/day
• Placebo Comparator: Placebo
  • 25 women 60 to 75 years of age receiving placebo once a day for 14 weeks

Primary Measures

• Change in bone mineral density
  • Time Frame: Before and after treatment
    Safety Issue?: No

Secondary Measures

• Change in bone marrow fat content
  • Time Frame: Before and after treatment
    Safety Issue?: No
• change in biochemical markers of bone turnover
  • Time Frame: Before and after treatment
    Safety Issue?: No
• Change in gene expression in bone marrow and fat cells
  • Time Frame: Before and after treatment
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 60 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: University of Aarhus

Overall Clinical Trial Officials and Contacts

Torben Harsløf, Dr. Principal Investigator Aarhus University Hospital  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00609362

Study ID Number: 2007-223

ClinicalTrials.gov Identifier: NCT00609362

Health Authority: Denmark: The Danish National Committee on Biomedical Research Ethics