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 Overview

• Status: Completed
• Conditions: Change in Bone Mineral Density; Change in Bone Marrow Fat Content
• Intervention / Treatment: Drug: Rosiglitazone; Drug: Placebo pill

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8000 C
    • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Rosiglitazone; 25 women age 60 to 75 years receiving rosiglitazone 8 mg/day	Drug: Rosiglitazone; one tablet of rosiglitazone 8 milligrams per day for 14 weeks; Other Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	BMD measured at baseline and after 14 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Measured at baseline and after 14 weeks of treatment
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).	At baseline and after 14 weeks of treatment
Change in Gene Expression in Bone Marrow and Fat Cells		Before and after treatment

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Torben Harsløf, Dr., Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: January 24, 2008
• First Submitted That Met QC Criteria: February 6, 2008
• First Posted (Estimate): February 7, 2008

Study Record Updates

• Last Update Posted (Estimate): April 27, 2011
• Last Update Submitted That Met QC Criteria: March 29, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: Rosiglitazone; BMD; Bone marrow fat
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Rosiglitazone
• Other Study ID Numbers: 2007-223