Thiazolidinediones (TZD) Bone Loss and the Effects on Bone Marrow Differentiation and Osteoblast Formation

Thiazolidinedione-Induced Bone Loss: Effects on Bone Marrow Stromal Cell Differentiation Capacity and Osteoblast Formation

Thiazolidinediones (TZDs) are a commonly used antidiabetic drugs currently used by over a million patients in the United States. Recent studies have shown that treatment with TZD may increase the risk of bone fractures. The cause of bone loss is not known. We believe that TZD may cause increased accumulation of fat in the bone marrow, which may cause decrease bone formation and weak bones. .

This study aims to determine if TZDs increase the amount of fat and decrease the number of bone producing cells in the bone marrow.

A total of 5 subjects who require surgery for mandible (jaw) fracture and bone graft will be recruited. Some patients who will undergo mandible surgery will require a bone graft. In this procedure, a small piece of bone from the hip is placed in the mandible. In this study, a small amount of bone marrow fluid (5 mL or 1 teaspoon) will be obtained after the bone graft is completed. Obtaining the bone marrow will not result in additional pain or health problems. The effect of TZD on bone marrow and bone forming cells will be studied. The cells obtained during surgery will be grown at Dr Beck's laboratory at Emory University School of Medicine.

A working hypothesis suggests that the increased fracture risk in patients taking TZDs is the result of TZDs altering the differentiation capacity of bone marrow stromal cells pushing them towards the adipocyte lineage at the cost of osteoblast formation thereby decreasing bone formation.

Study AIM:To determine whether TZD exposure in vitro alters bone formation and the differentiation capacity of bone marrow stromal cells by promoting adipocyte lineage differentiation and lowering osteoblast formation.

Inclusion Criteria:

1. Males or females between the ages of 18 and 80 years undergoing ileac crest bone graft to repair traumatic mandible fracture.
2. Patients admitted for elective or emergency surgery or trauma.

Exclusion Criteria:

1. Subjects with history of decompensated diabetes (blood glucose > 200 mg/dl)
2. Critically ill patients with multi-organ failure, relevant hepatic disease or impaired renal function (serum creatinine ≥ 2.0 mg/dl)
3. HIV
4. Hemolytic anemia and/or hematocrit < 28%
5. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
6. Pregnancy