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