OsteoporosisNCT00467285
Effect of Diabetic Medications on Bone Metabolism
An observational study of Osteoporosis and Type 2 Diabetes Mellitus, run by VA Office of Research and Development.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Osteoporosis, Type 2 Diabetes Mellitus
- How many people
- 96 participants
- Where
- No sites listed yet
- Study dates
- Oct 2006to Sep 2009
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: subjects with type 2 diabetes and less than 55 years with or without pioglitazone as part of their therapy for diabetes
Who may be able to join
- 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)
Who cannot join
- 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).
About this study
Official title: Effect of Thiazolidinediones on Skeletal Health
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.
Read the detailed description
The prevalence rate of diabetes among veterans is 16% in general and 27% at out medical center compared to 6.3% among United States population. Subjects with diabetes and prediabetes said to have increased bone loss 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. Most of the pleiotropic effects of teh thiazolidinediones are beneficial in atherosclerosis and cancer, in addition to improving insulin resistance. Data from studies in mice show that rosiglitazone and pioglitazone therapy results in a significant decrease in total body bone mineral density was observed. Whether it is true in humans is not clear. There are no prospective studies to date. Subjects with diabetes are already at an increased risk for femoral fractures. If the animal data can be can be extrapolated to humans, thiazolidinedione pioglitazone may result in significant risk of adverse skeletal effects. This study hypothesizes that treatment with the thiazolidinedione pioglitazone may result in a significant reduction in bone mineral density. The aims of the study include: 1. To prospectively evaluate the effect of pioglitazone on skeletal health, we will study 140 subjects with diabetes receiving pioglitazone as part of their diabetes management and compare them with 140 diabetic controls (matched for age, sex, body mass index (BMI), smoking and alcohol history), not treated with pioglitazone. 2. To measure the bone mineral density by DXA at AP spine and hip, as well as bone turnover markers-procollagen type 1C-terminal propeptide (P1CP), and procollagen type 1N-terminal propeptide (P1NP), bone specific alkaline phosphatase, osteocalcin, plasma C-telopeptide (CTx) and N-telopeptide (NTx) at baseline, six and 12 months of follow-up. 3. To determine the change in BMD and bone turnover markers within each group from baseline to follow-up at six and 12 months. 4. To compare the changes in the BMD and bone turnover markers between groups at baseline and follow-up at six and 12 months.
Subjects: Prospectively study 140 subjects with type 2 diabetes and on pioglitazone, age, and sex matched controls.
Sample Size: The sample size is based on the primary objective of comparing the levels bone turnover markers and bone mineral density changes in diabetes with or without avandia.
Number of visits: 140 subjects with diabetes and on pioglitazone and 140 subjects with diabetes not on pioglitazone
- Subjects will be studies at three visits.
- The procedures to be done include assessment of bone mineral density measurement by dual X-ray absorptiometry (DXA), measurement of bone turnover markers like serum osteocalcin and urinary N-telopeptide after the informed consent. About 15ml (one tablespoonful) of blood will be drawn at each visit for the study.
- All the baseline measurements will be repeated at 6 months and at one year.
- Statistical analysis of the data will be done to compare the changes in bone turnover markers and bone mineral density between the two groups.
Site of the study: Overton Brooks VAMC Diabetics clinic and Primary care clinics.
If our hypothesis is proven correct, subjects with diabetes requiring thiazolidinediones should have bone turnover markers and BMD measurement at baseline and have serial follow up. Identification of subjects at high risk will allow health care providers to initiate necessary protective measures to protect the bone to decrease the fracture risk.
Potential Impact on Veterans Health Care: Identification of subjects at high risk will allow health care providers to initiate necessary preventive measures to protect the bone and decrease the risk of fractures, or avoid the use of TZDs altogether in select patients. Since the prevalence of diabetes is very high among veterans, evaluation of a possible risk of skeletal health with the use of pioglitazone is highly relevant to VA health care.
- Conditions
- Osteoporosis, Type 2 Diabetes Mellitus
- Keywords
- Bone Density, C-telopeptide, Dual-Energy X-Ray Absorptiometry, N-telopeptide, Osteocalcin, Osteoporosis, Thiazolidinediones, Type 2 Diabetes Mellitus
- Medical subject headings
- Osteoporosis, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | 140 subjects with type 2 diabetes on pioglitazone. | |
| Group 2 | 140 subjects with type 2 diabetes not on pioglitazone. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in BMD at Femoral Neck
% 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
Measured: 6 months
Changes in BMD Total Hip
% change at 6 month follow up compared to baseline
Measured: 6 months
Changes in BMD AP Spine
% change in BMD at 6 month follow up compared to baseline
Measured: 6 months
Changes in BMD 0.33 Radius
% change in BMD at 6 month follow up compared to baseline
Measured: 6 months
Secondary outcomes (3)
CTx
% Change in bone turnover markers at 6 month follow up compared to baseline
Measured: 6 months
Osteocalcin
% change at 6 month follow up compared to baseline
Measured: 6 months
Changes in CTx at Follow up
% change in the levels of CTx at 6 months follow up compared to baseline
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2007 (estimated)
- Study startOct 2006
- Primary completionSep 2009
- Study completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Subhashini Yaturu, MD, Principal investigator, Albany VA Medical Center Samuel S. Stratton, Albany, NY
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00467285
- Sponsor's protocol ID
- ENDB-019-06S
- Status last verified
- Jul 2026
- First submitted
- 26 Apr 2007
- Last updated
- 13 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Thiazolidinediones on Skeletal Health
- ClinicalTrials.gov ID
- NCT00467285
- Acronym / sponsor ID
- ENDB-019-06S
- Conditions
- Osteoporosis, Type 2 Diabetes Mellitus
- Keywords
- Bone Density, C-telopeptide, Dual-Energy X-Ray Absorptiometry, N-telopeptide, Osteocalcin, Osteoporosis, Thiazolidinediones, Type 2 Diabetes Mellitus
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- Oct 2006
- Primary completion
- Sep 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 30 Apr 2007 (estimated)
- Results
- Posted 14 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The prevalence rate of diabetes among veterans is 16% in general and 27% at out medical center compared to 6.3% among United States population. Subjects with diabetes and prediabetes said to have increased bone loss 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. Most of the pleiotropic effects of teh thiazolidinediones are beneficial in atherosclerosis and cancer, in addition to improving insulin resistance. Data from studies in mice show that rosiglitazone and pioglitazone therapy results in a significant decrease in total body bone mineral density was observed. Whether it is true in humans is not clear. There are no prospective studies to date. Subjects with diabetes are already at an increased risk for femoral fractures. If the animal data can be can be extrapolated to humans, thiazolidinedione pioglitazone may result in significant risk of adverse skeletal effects. This study hypothesizes that treatment with the thiazolidinedione pioglitazone may result in a significant reduction in bone mineral density. The aims of the study include: 1. To prospectively evaluate the effect of pioglitazone on skeletal health, we will study 140 subjects with diabetes receiving pioglitazone as part of their diabetes management and compare them with 140 diabetic controls (matched for age, sex, body mass index (BMI), smoking and alcohol history), not treated with pioglitazone. 2. To measure the bone mineral density by DXA at AP spine and hip, as well as bone turnover markers-procollagen type 1C-terminal propeptide (P1CP), and procollagen type 1N-terminal propeptide (P1NP), bone specific alkaline phosphatase, osteocalcin, plasma C-telopeptide (CTx) and N-telopeptide (NTx) at baseline, six and 12 months of follow-up. 3. To determine the change in BMD and bone turnover markers within each group from baseline to follow-up at six and 12 months. 4. To compare the changes in the BMD and bone turnover markers between groups at baseline and follow-up at six and 12 months.
Subjects: Prospectively study 140 subjects with type 2 diabetes and on pioglitazone, age, and sex matched controls.
Sample Size: The sample size is based on the primary objective of comparing the levels bone turnover markers and bone mineral density changes in diabetes with or without avandia.
Number of visits: 140 subjects with diabetes and on pioglitazone and 140 subjects with diabetes not on pioglitazone
- Subjects will be studies at three visits.
- The procedures to be done include assessment of bone mineral density measurement by dual X-ray absorptiometry (DXA), measurement of bone turnover markers like serum osteocalcin and urinary N-telopeptide after the informed consent. About 15ml (one tablespoonful) of blood will be drawn at each visit for the study.
- All the baseline measurements will be repeated at 6 months and at one year.
- Statistical analysis of the data will be done to compare the changes in bone turnover markers and bone mineral density between the two groups.
Site of the study: Overton Brooks VAMC Diabetics clinic and Primary care clinics.
If our hypothesis is proven correct, subjects with diabetes requiring thiazolidinediones should have bone turnover markers and BMD measurement at baseline and have serial follow up. Identification of subjects at high risk will allow health care providers to initiate necessary protective measures to protect the bone to decrease the fracture risk.
Potential Impact on Veterans Health Care: Identification of subjects at high risk will allow health care providers to initiate necessary preventive measures to protect the bone and decrease the risk of fractures, or avoid the use of TZDs altogether in select patients. Since the prevalence of diabetes is very high among veterans, evaluation of a possible risk of skeletal health with the use of pioglitazone is highly relevant to VA health care.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | – | –140 subjects with type 2 diabetes on pioglitazone. |
| Group 2 | – | –140 subjects with type 2 diabetes not on pioglitazone. |
Who may qualify
- Ages
- 30 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- subjects with type 2 diabetes and less than 55 years with or without pioglitazone as part of their therapy for diabetes
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
Changes in BMD Total Hip
Time frame: 6 months
% change at 6 month follow up compared to baseline
Changes in BMD AP Spine
Time frame: 6 months
% change in BMD at 6 month follow up compared to baseline
Changes in BMD 0.33 Radius
Time frame: 6 months
% change in BMD at 6 month follow up compared to baseline
3 secondary outcomes
CTx
Time frame: 6 months
Osteocalcin
Time frame: 6 months
Changes in CTx at Follow up
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publicationYaturu 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.
- Results publicationYaturu 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.
- journal web site with link to the articleLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Subhashini Yaturu, MD principal investigator
Albany VA Medical Center Samuel S. Stratton, Albany, NY
Questions about this trial
What is this clinical trial studying?
An observational study of Osteoporosis and Type 2 Diabetes Mellitus, run by VA Office of Research and Development.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in BMD at Femoral Neck (time frame: 6 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00467285, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2026.