Effect of Diabetic Medications on Bone Metabolism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00467285
Recruitment Status : Completed
First Posted : April 30, 2007
Results First Posted : January 14, 2015
Last Update Posted : January 14, 2015
Information provided by (Responsible Party):
VA Office of Research and Development ( US Department of Veterans Affairs )

Brief Summary:
Subjects with diabetes and pre-diabetes are said to have increased bone loss when compared to the general population. Pioglitazone a thiazolidinedione, is a Food and Drug Administration (FDA) approved oral anti-diabetic agent for the treatment of type 2 diabetes. Though there are many benefits for using thiazolidinediones in the treatment of type 2 diabetes, there is data that indicates that rosiglitazone therapy results in a significant decrease in total body bone mineral density in mice. Whether it is true in humans is not clear. If the animal data can be extrapolated to humans, thiazolidinediones may pose a significant risk of adverse effects on bone. This study hypothesizes that treatment with the thiazolidinedione pioglitazone may result in significant reduction in bone mineral density. The aims of this are: 1. to evaluate the effect of pioglitazone on skeletal health; 2. to measure the bone mineral density (BMD) of the spine and hip, as well as bone turnover markers, at different times of persons taking thiazolidinediones and others not taking them; 3. to determine the change in BMD and bone turnover markers within different groups at different times; and 4. to compare these changes.

Condition or disease
Osteoporosis Type 2 Diabetes Mellitus

  Show Detailed Description

Study Type : Observational
Actual Enrollment : 96 participants
Observational Model: Case Control
Time Perspective: Prospective
Official Title: Effect of Thiazolidinediones on Skeletal Health
Study Start Date : October 2006
Actual Primary Completion Date : September 2009
Actual Study Completion Date : September 2009

Resource links provided by the National Library of Medicine

Group 1
140 subjects with type 2 diabetes on pioglitazone.
Group 2
140 subjects with type 2 diabetes not on pioglitazone.

Primary Outcome Measures :
  1. Changes in BMD at Femoral Neck [ Time Frame: 6 months ]
    % changes in BMD ( BMD at Lumbar spine, femoral neck and 0.33 radius) and bone turn over markers in subjects with diabetes on pioglitazone compared to those who are not on Pioglitazone

  2. Changes in BMD Total Hip [ Time Frame: 6 months ]
    % change at 6 month follow up compared to baseline

  3. Changes in BMD AP Spine [ Time Frame: 6 months ]
    % change in BMD at 6 month follow up compared to baseline

  4. Changes in BMD 0.33 Radius [ Time Frame: 6 months ]
    % change in BMD at 6 month follow up compared to baseline

Secondary Outcome Measures :
  1. CTx [ Time Frame: 6 months ]
    % Change in bone turnover markers at 6 month follow up compared to baseline

  2. Osteocalcin [ Time Frame: 6 months ]
    % change at 6 month follow up compared to baseline

  3. Changes in CTx at Follow up [ Time Frame: 6 months ]
    % change in the levels of CTx at 6 months follow up compared to baseline

Biospecimen Retention:   Samples Without DNA
Urine and serum samples collected for the study will be spin and stored at -70 degree C and assays run intermittently

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Ages Eligible for Study:   30 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
subjects with type 2 diabetes and less than 55 years with or without pioglitazone as part of their therapy for diabetes

Inclusion Criteria:

  • Age 30-55 years
  • Gender: men and women
  • Ethnicity: all ethnic groups
  • 140 subjects with diabetes and no pioglitazone (recently started i.e. less than 3 months as well as those who have just initiated pioglitazone treatment)
  • 140 control subjects (subjects with diabetes and not on pioglitazone) will be included
  • The control subjects will be chosen to match age, sex, ethnicity and comparable smoking and alcohol history
  • To avoid confusion factor of vitamin D and calcium intake, all the subjects will be given vitamin D and calcium supplements (USDA recommended doses)

Exclusion Criteria:

  • Patients who are unable or unwilling yo give informed consent
  • Immobilized or bed bound subject
  • Subjects wil known diseases associated with disordered bone metabolism such as chronic renal insufficiency, chronic steroid use, primary hyperparathyroidism, untreated subclinical or clinical hyperthyroidism and Paget's disease. To identify subjects with decreased Glomerular filtration rate (GFR) even if creatinine is normal will be excluded (at the proposed study site, routine bm includes calculated GFR from the chemistry lab)
  • Patients on medications that will alter bone metabolism will be excluded. They are glucocorticoids, gonadal hormones (testosterone in men and estrogen in women).
  • Subjects with known history of chronic pancreatitis, pancreatectomy or malabsorption syndromes to avoid confounding factors known to affect vitamin D metabolism and indirectly bone mineral metabolism.
  • Female patients with perimenopause or menopause: history of hypogonadism (History of ovariectomy or postmenopausal women) to avoid bone turn over changes secondary to hypogonadism. Perimenopausal women identifies by screening FSH and LH and excluding women with elevated FSH be excluded to avoid perimenopausal effect on bone turnover (women over 35 will still have a screening gonadal hormonal evaluation).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00467285

Sponsors and Collaborators
US Department of Veterans Affairs
Principal Investigator: Subhashini Yaturu, MD Albany VA Medical Center Samuel S. Stratton, Albany, NY

Additional Information:
Publications of Results:
Yaturu S, Dier U, Cui H, Mousa SA. Aspirin resistance in young men with Type 2 diabetes. Journal of diabetes mellitus. 2014 Jan 1; 4(1):72-6.
Yaturu S, Davis J, Shi R. Decreased bone mineral density in young male veterans on Pioglitazone*. Journal of diabetes mellitus. 2012 Jan 1; 2(1):35-9.

Responsible Party: US Department of Veterans Affairs Identifier: NCT00467285     History of Changes
Other Study ID Numbers: ENDB-019-06S
First Posted: April 30, 2007    Key Record Dates
Results First Posted: January 14, 2015
Last Update Posted: January 14, 2015
Last Verified: January 2015

Keywords provided by VA Office of Research and Development ( US Department of Veterans Affairs ):
Bone Density
Dual-Energy X-Ray Absorptiometry
Type 2 Diabetes Mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Hypoglycemic Agents
Physiological Effects of Drugs