Effects of Thiazolidinediones on Human Bone Marrow Stromal Cell Differentiation Capacity:In Vitro and In Vivo- A Pilot Study

E2a. Screening: Prescreening of electronic medical records will be used as much as possible to reduce screen failure rates. Patients will undergo a full history (with special focus on inclusion and exclusion criteria), physical exam, and blood draw. Lab work will consist of CBC, PT, PTT, CMP, HbA1c, PTH, serum beta-HCG in females of childbearing potential and testosterone in males. We will measure 25(OH) Vitamin D at baseline and completion of the study.

E2b. Study visits Subjects will be admitted to the Grady GCRC after an overnight fast at the initial visit and at 26 weeks. Study drug will be dispensed at the initial visit. At the initial visit and at 26 weeks, subjects will undergo bone marrow aspiration by a skilled and certified Hematology Oncology fellow, bone densitometry (DXA) of their hip and spine, and a blood.draw (5mls).

Subjects will be seen in follow-up at the Grady GCRC at 2 weeks and every 4 weeks thereafter for measurement of body weight, vital signs, and targeted history looking for any side effects from study drugs.

Study drug will be dispensed to patients at baseline and on monthly follow-up visits thereafter. To assess compliance, subjects will be instructed to return any unused drug, and if the subject takes less than 75% of the study medication, the patient will be withdrawn from the study. Patients will be monitored closely for development of side effects. Glycemic control will be assessed with HbA1c measurements at baseline, 12 weeks into the study and at end of study. Home blood sugars, fasting and occasional postprandial blood sugars will be assessed at each of the study visits.

E2b.2. Bone Marrow Biopsy aspiration: Bone marrow (BM) aspiration will be done by a hematology and oncology fellow, Dr. Simbo Aduloju, who is certified in doing these procedures at the Grady GCRC. Subjects will be pre-medicated 30 minutes prior to the procedure with oral Lorazepam 2mg and Tylenol 500mg for analgesia.The only absolute contraindication to BM aspirations is the presence of bleeding disorders. During the screening process, patients will be asked about a history of coagulopathies such as hemophilia. In addition all patients will have their PT, PTT and platelets checked at baseline. Under sterile technique and after local anesthesia with 2% lidocaine, 5mls of bone marrow will be aspirated from the posterior iliac crest using a 16 gauge bone marrow aspiration needle attached to a 10 ml syringe. The sample will be placed on ice immediately and transported to the lab of Dr. George Beck. After the procedure, manual pressure will be applied to the aspiration site for a minimum of 5 minutes to prevent bleeding. Patients blood pressure will be checked after the procedure and prior to their departure from the GCRC to ensure absence of hypotension due to lorazepam.