Atherosclerosis, Cardiovascular Diseases, Coronary Disease, Diabetes Mellitus, Hypercholesterolemia, Hypertension
Conditions
Keywords
Diabetes Mellitus, Fracture, Falls, Height Loss
Brief summary
The purpose of the ACCORD-BONE Study is to investigate the effects of intensive glycemic control for type 2 diabetes (in ACCORD participants) on factors related to bone health, including, fractures, falls, and bone mineral density.
Detailed description
Recent studies have established that type 2 diabetes is a risk factor for fractures, particularly of the hip, shoulder and foot. Additionally, type 2 diabetes is associated with a 50-60% increase in the risk of falling. The higher risk of fracture associated with type 2 diabetes is an important health burden for these patients. More frequent falls and perhaps reduced bone strength in those with diabetes are thought to be key contributing factors. The best approach to preventing fractures in type 2 diabetes is not yet understood. There is observational evidence to support our hypothesis that better glycemic control will preserve bone and reduce falls and fractures. The ACCORD-BONE study provides a unique opportunity to determine whether intensive glycemic control will prevent fractures, falls, and bone loss in older diabetic adults, which may lead to improved treatment and prevention in the future.
Interventions
DRUGhypoglycemic agents, hydroxymethylglutaryl-CoA Reductase inhibitors, hypertensive agents
type 2 diabetes treatments, per standard of care
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Fulfills criteria for inclusion in the ACCORD main trial * Must have been randomized into the ACCORD study and be a participant from the five CCNs in the ACCORD-BONE ancillary study.
Exclusion criteria
* Fulfills criteria for exclusion in the ACCORD main trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Non-vertebral Fracture | Average follow-up of 3.8 years | The BONE ancillary study was initiated during recruitment for the main ACCORD trial. Beginning in January 2006, at the next annual visit participants were asked about the occurrence of any non-spine fractures since randomization. After the annual visit in 2006, participants were asked if they had suffered a fracture since their last annual visit. Reported fracture events were centrally adjudicated, based on radiology records, at the University of California, San Francisco (UCSF) with the adjudicators blinded to treatment assignment. |
| Number of Participants With at Least One Fall | Average follow-up of 2.0 years | At each annual visit starting in January 2006, participants were also asked about falling: In the last 12 months have you fallen and landed on the floor or ground, OR fallen and hit an object like a table or stair? Those who answered yes were also asked how many times they had fallen in the previous 12 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With > 2 cm of Height Loss | 5 years | Standing height was measured according to a standard protocol at baseline and annual visits on all ACCORD participants. Height loss was compared by treatment assignment using linear mixed models with random intercepts and slopes. Treatment effects were captured by the interaction between treatment assignment and time. The proportions losing \>2 cm of height during follow-up were compared using logistic models. This degree of height loss is associated with incident vertebral fracture with 94% specificity but only 28% sensitivity |
Countries
Canada, United States
Participant flow
Recruitment details
The ACCORD trial has been described previously (Buse JB,et al. Am J Cardiol 99:21i-33i, 2007). Five of the 7 clinical center networks agreed to participate in the BONE ancillary study, including 54 of 77 clinical sites and 7,287 participants. The BONE ancillary study was initiated during the main recruitment for ACCORD (beginning in 2006).
Participants by arm
| Arm | Count |
|---|---|
| Intensive Glycemic Control intensive therapeutic strategy targeting normal glycated hemoglobin (A1C) levels (i.e., below 6.0%)in a population with long-standing type 2 diabetes and a history of cardiovascular disease or significant cardiovascular risk factors | 3,655 |
| Standard Glycemic Control standard strategy targeting A1C levels from 7.0 to 7.9% in a population with long-standing type 2 diabetes and a history of cardiovascular disease or significant cardiovascular risk factors | 3,632 |
| Total | 7,287 |
Baseline characteristics
| Characteristic | Intensive Glycemic Control | Standard Glycemic Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1275 Participants | 1271 Participants | 2546 Participants |
| Age, Categorical Between 18 and 65 years | 2380 Participants | 2361 Participants | 4741 Participants |
| Age Continuous | 62.5 years STANDARD_DEVIATION 6.7 | 62.6 years STANDARD_DEVIATION 6.7 | 62.5 years STANDARD_DEVIATION 6.7 |
| Region of Enrollment Canada | 752 participants | 756 participants | 1508 participants |
| Region of Enrollment United States | 2903 participants | 2876 participants | 5779 participants |
| Sex: Female, Male Female | 1267 Participants | 1251 Participants | 2518 Participants |
| Sex: Female, Male Male | 2388 Participants | 2381 Participants | 4769 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Number of Participants With at Least One Fall
At each annual visit starting in January 2006, participants were also asked about falling: In the last 12 months have you fallen and landed on the floor or ground, OR fallen and hit an object like a table or stair? Those who answered yes were also asked how many times they had fallen in the previous 12 months.
Time frame: Average follow-up of 2.0 years
Population: These analyses include results from the annual visits that occurred before Feb 5, 2008, the close of the intensive glycemia arm. Of those in the BONE ancillary study, 6,782 participants answered at least one question about falls.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intensive Glycemic Control | Number of Participants With at Least One Fall | 1122 participants |
| Standard Glycemic Control | Number of Participants With at Least One Fall | 1133 participants |
Comparison: Number of participants with falls reported at each annual visit were compared by treatment assignment using a repeated-measures negative binomial model, with robust standard errors to account for clustering of the repeated outcomes within participants; the log of the length of the reporting period varied slightly and was included as an offsetp-value: 0.4995% CI: [0.84, 1.43]Regression, Cox
Primary
Number of Participants With at Least One Non-vertebral Fracture
The BONE ancillary study was initiated during recruitment for the main ACCORD trial. Beginning in January 2006, at the next annual visit participants were asked about the occurrence of any non-spine fractures since randomization. After the annual visit in 2006, participants were asked if they had suffered a fracture since their last annual visit. Reported fracture events were centrally adjudicated, based on radiology records, at the University of California, San Francisco (UCSF) with the adjudicators blinded to treatment assignment.
Time frame: Average follow-up of 3.8 years
Population: As per protocol, pathological fractures, confirmed as occurring secondary to neoplasm, necrosis, or sepsis, and periprosthetic fractures were excluded (N=7). These analyses are limited to confirmed fractures that occurred on or before Feb 5, 2008, when the intensive glycemia intervention was ended.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intensive Glycemic Control | Number of Participants With at Least One Non-vertebral Fracture | 198 participants |
| Standard Glycemic Control | Number of Participants With at Least One Non-vertebral Fracture | 189 participants |
Comparison: The BONE ancillary study was designed to have 80% power to detect a relative reduction in risk of non-spine clinical fractures of 22-29%. This was based on an estimated total number of fractures between 259-494, calculated with the following assumptions: rate of clinical non-spine fracture among women in the standard glycemia therapy group between 15 and 25/1000 person yrs, fracture rates for men between 35-40% of the rates for women of the same age, and an avg follow-up time of 4.6 yrs.p-value: 0.67895% CI: [0.86, 1.27]Regression, Cox
Secondary
Number of Participants With > 2 cm of Height Loss
Standing height was measured according to a standard protocol at baseline and annual visits on all ACCORD participants. Height loss was compared by treatment assignment using linear mixed models with random intercepts and slopes. Treatment effects were captured by the interaction between treatment assignment and time. The proportions losing \>2 cm of height during follow-up were compared using logistic models. This degree of height loss is associated with incident vertebral fracture with 94% specificity but only 28% sensitivity
Time frame: 5 years
Population: Among participants in the BONE ancillary study, 6,979 participants had at least one height measurement during follow-up and were included in these analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intensive Glycemic Control | Number of Participants With > 2 cm of Height Loss | 678 participants |
| Standard Glycemic Control | Number of Participants With > 2 cm of Height Loss | 686 participants |
Comparison: Height loss was compared by treatment assignment using linear mixed models with random intercepts and slopes. The proportions losing \>2 cm of height during follow-up were compared using logistic models. Based on previous research by Siminoski et al., this degree of height loss is associated with incident vertebral fracture with 94% specificity but only 28% sensitivity.(Siminoski K, Jiang G, Adachi JD, et al. Osteoporos Int 2005;16:403-410)p-value: 0.85495% CI: [0.88, 1.11]Mixed Models Analysis