News & Research

University of Toledo Health Science Campus Toledo, Ohio

Prevention of TZD-induced bone loss and improvement of TZD-affected bone fracture healing

General Research Subject: Type 2 Diabetes

Focus: Signal Transduction (Non-Insulin Action)\Hormones, Signal Transduction (Non-Insulin Action)\Transcriptional Regulation

Type of Grant: Basic Science

Project Start Date: January 1, 2009

Project End Date: June 30, 2012

Research Description

Funded by the Order of the Amaranth

Anti-diabetic drugs, thiazolidinediones (TZDs), improve insulin sensitivity and glucose metabolism. Unfortunately, these drugs may have a negative effect on bone in some of the diabetic patients.  They induce bone loss and increase the frequency of bone fractures in older diabetic women. In mice, TZDs cause bone loss and delay bone fracture healing. TZDs interact with a single protein, named PPARgamma, which controls both sugar levels and bone mass.  In order to prevent TZD-caused bone loss and improve bone fracture healing in diabetic patients on TZD therapy, the following studies are proposed: 1) Examine whether anti-osteoporotic drugs may prevent bone loss caused by TZD therapy, 2) Improve bone fracture healing by eliminating PPARgamma, the protein target of TZDs, exclusively in the fracture site. 

These studies will be performed in female mice of different ages and estrogen status. Estrogen status will be manipulated by removing ovaries in some mice to model a postmenopausal state. These studies will provide information crucial to developing therapies to prevent TZD-associated bone loss and improve bone fracture healing in older diabetic women. These studies are especially important because older diabetic women already have a high risk of bone loss due to aging and a lack of estrogen hormone.

Reseacher Profile

What area of diabetes research does your project cover?  What role will this particular project play in preventing, treating and/or curing diabetes? 

My project focuses on researching pharmacological methods to prevent bone loss which is associated with a use of anti-diabetic drugs, thiazolidinediones (TZDs). TZDs are very effective in lowering and controlling blood glucose levels in patients with type 2 diabetes. Unfortunately, these drugs may have a negative effect on bone in some of the diabetic patients.  TZDs induce bone loss and increase the frequency of bone fractures in older diabetic women. They also may cause a delay in healing of bone fractures.

In order to prevent TZD-caused bone loss and improve bone fracture healing in diabetic patients on TZD therapy, the following studies are proposed: 1) Examine whether anti-osteoporotic drugs, commonly used in clinics, may be used as an accompany therapy to TZDs therapy to prevent bone loss in diabetic patients, 2) Study the methods to improve bone fracture healing in diabetic patients on TZD therapy by stimulating bone formation exclusively in the fractured bone.  These studies will be performed in female mice of different ages and estrogen status. Estrogen status will be manipulated by removing ovaries in some mice to model a postmenopausal state. These studies will provide information crucial to developing therapies to prevent TZD-associated bone loss and improve bone fracture healing in older diabetic women on TZD therapy. These studies are especially important because older diabetic women already have a high risk of bone loss due to aging and a lack of estrogen hormone.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond? 

These studies will improve safety of the patients, which are on TZD therapy. They will provide a means to prevent bone loss in those patients, which are at a risk of TZD-induced bone loss, especially older diabetic women. In general diabetic patients, regardless of TZD use, are at increased risk of bone fractures and TZD therapy may augment this risk. Our studies are also addressing the question how to improve healing of fractured bone in diabetic patients on TZD therapy.

Why is it important for you, personally, to become involved in diabetes research?  What role will this award play in your research efforts? 

I have a long interest in the research, which investigates bone status in diabetic patients. I had started this research in 1995 and had found that some of the anti-diabetic therapies may increase bone loss in diabetic patients. This led me to the conclusion that diabetes and osteoporosis may share common mechanisms, which have to be addressed during development of new anti-diabetic therapies. In light of the prevalence of diabetes and osteoporosis in our society, I strongly believe that research which integrates these two diseases will significantly contribute to the better health care for patients which suffer diabetes.  This is my second research award from the American Diabetes Association to investigate skeletal complications in diabetic disease. I am honored and very grateful to the Association for its vision and dedication to improve health of diabetic patients.

In what direction do you see the future of diabetes research going? 

Diabetes is a very complex disease which affects every organ in the body, including bone. I see the future of diabetes research in developing interdisciplinary and system physiology approaches, which will allow for development of the therapies controlling not only blood glucose levels but being also beneficial in controlling functions of other organs. Such approach will improve the safety of already existing and newly developed drugs to combat diabetic disease.