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

Osteoporosis Clinical Trial

— TZDBONE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00663143
• Other study ID #: IRB00006692
• Status: Completed
• Phase: N/A
• First received: April 18, 2008
• Last updated: March 30, 2015
• Start date: July 2009
• Est. completion date: December 2010

Study information

• Verified date: March 2015
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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. .

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: December 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Osteoporosis

Intervention

Procedure:
• Stromal Cells Sample
Human Bone Marrow Stromal Cells will be obtained from 5 patients. Stromal cells will be obtained from subjects undergoing bone graft procedure to repair traumatic mandible fractures. Bone graft specimens will be obtained from the ileac crest. This will allow easy access to bone marrow specimen without additional pain or complications. A total of 5 ml of bone marrow will be obtained from each patient.

Locations

Country	Name	City	State
United States	Emory Crawford Long Hospital	Atlanta	Georgia
United States	Emory University Hospital	Atlanta	Georgia
United States	Grady Memorial Hospital	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Emory University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		once all subjects have been recruited	Yes