Thiazolidinediones (TZD) Bone Loss and the Effects on Bone Marrow Differentiation and Osteoblast Formation - Full Text View

Sponsored by:	Emory University
Information provided by:	Emory University
ClinicalTrials.gov Identifier:	NCT00663143

Purpose

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.

Condition	Intervention
Osteoporosis	Procedure: Stromal Cells Sample

MedlinePlus related topics: Bone Grafts Fractures Osteoporosis Surgery

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Thiazolidinedione-Induced Bone Loss: Effects on Bone Marrow Stromal Cell Differentiation Capacity and Osteoblast Formation

Further study details as provided by Emory University:

Primary Outcome Measures:

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 [ Time Frame: once all subjects have been recruited ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	5
Study Start Date:	May 2008
Estimated Study Completion Date:	June 2009
Estimated Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Intervention Details:

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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00663143

Contacts

Contact: Guillermo Umpierrez, MD	404.778.1665	geumpie@emory.edu
Contact: Dawn Smiley, MD	404.778.1664	dsmiley@emory.edu

Locations

United States, Georgia
Grady Memorial Hospital	Not yet recruiting
Atlanta, Georgia, United States, 30303
Contact: Guillermo Umpierrez, MD 404-778-1665 geumpie@emory.edu
Contact: Dawn Smiley, MD 4047781664 dsmiley@emory.edu
Principal Investigator: Guillermo Umpierrez, MD
Emory Crawford Long Hospital	Recruiting
Atlanta, Georgia, United States, 30308
Contact: Gary Boloux, MD 404-778-4500 gbouloux@hotmail.com
Contact: Guillermo Umpierrez, MD 404-778-1665 geumpie@emory.edu
Emory University Hospital	Recruiting
Atlanta, Georgia, United States, 30322
Contact: Gary Bouloux, MD/DDS 404-778-4500 gbouloux@hotmail.com
Contact: Guillermo Umpierrez, MD 404-778-1665 geumpie@emory.edu

Sponsors and Collaborators

Emory University

Investigators

Principal Investigator:

Guillermo Umpierrez, MD

Emory University SOM

More Information

No publications provided

Responsible Party:	Emory University School of Medicine ( Guillermo Umpierrez, MD )
Study ID Numbers:	e6692, IRB#e6692
Study First Received:	April 18, 2008
Last Updated:	February 2, 2009
ClinicalTrials.gov Identifier:	NCT00663143 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Emory University:

investigate
if TZD exposure
in vitro
alters
bone

formation
differentiation
capacity
bone marrow
stromal cells

Study placed in the following topic categories:

Hypoglycemic Agents
Musculoskeletal Diseases
2,4-thiazolidinedione

Osteoporosis
Bone Diseases, Metabolic
Bone Diseases

Additional relevant MeSH terms:

Hypoglycemic Agents
Musculoskeletal Diseases
Physiological Effects of Drugs
2,4-thiazolidinedione

Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 07, 2009