Bone Loss
Conditions
Keywords
bone, adaptation, mechanical stimuli, women, peak bone mass
Brief summary
The purpose of this study is to understand how different types of mechanical forces can influence bone adaptation (and make bones stronger, potentially). Forces acting on bones cause mechanical strain. In small animals, strain magnitude and rate have been shown to stimulate bone adaptation. This study is designed to test the degree to which strain magnitude and rate govern bone adaptation in healthy adult women.
Detailed description
The study consists of three Aims: Aim 1: compare the effect on bone structure of mechanical signals with low strain magnitude, high strain magnitude, and control groups over a 12-month prospective period. Aim 2. Compare the effect on bone structure of mechanical signals with low strain rate, high strain rate, and control groups over a 12-month prospective period. Aim 3: Examine the effect of withdrawing mechanical signals, by measuring bone structure during the 12 months after the intervention is withdrawn. The intervention is a voluntary forearm compression task, consisting of leaning onto the palm of the hand to produce a target force. The primary outcome measure is change in distal radius bone mineral content (BMC).
Interventions
OTHERvoluntary forearm loading task
voluntary task, consisting of leaning onto the palm of the hand until a target force is reached. Each loading bout consists of 100 loading cycles, which takes approximately 2 minutes to complete. The task is performed 4 times per week during the intervention period.
Sponsors
Northwestern University
Worcester Polytechnic Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Masking description
all data were blinded for analysis
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Female * Age 21-40 * Body Mass Index \[18-29\] * 9-14 menstrual cycles/year * Dual energy X-ray Absorptiometry total radius bone mineral density (BMD) T-score \[-2.5-+1\] * Free of endocrinopathies * No known thyroid, vitamin D, or calcium abnormalities
Exclusion criteria
* Fracture to wrist \<5 years ago * Wrist Arthritis * Injury to the non-dominant elbow or shoulder \<5 years ago * Diabetes * Severe disabling conditions * Cancer \<5 years ago * Metabolic bone disease * Androgen, estrogen, progesterone, calcitonin, Selective Estrogen Receptor Modulators, Parathyroid hormone, gonadotropin-releasing hormone or analogs used \<6 months ago * Corticosteroids \<3 months ago * Bisphosphonates or fluoride \<3 years ago * Cardiovascular/pulmonary disease * Uncontrolled hypertension * Regular Tobacco use * Marijuana use \>1 time/week * Alcohol \>4 drinks/day * Pregnancy or lactation \<2 years ago * Plan to become pregnant or donate eggs within 1 year * Depot medroxyprogesterone acetate contraceptive \<6 months ago * Current participation in upper extremity loading sports (gymnastics, tennis, softball, hockey) \>2 times/month * Low calcium intake (avoiding dairy products without taking calcium supplement)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in UD iBMC | baseline and 12 months | 12-month change in ultra-distal integral bone mineral content, measured with quantitative computed tomography (QCT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in UD ecBMC | baseline and 12 months | 12-month change in ultra-distal endocortical bone mineral content, measured with quantitative computed tomography (QCT) |
| Change in UD tBMC | baseline and 12 months | 12-month change in ultra-distal trabecular bone mineral content, measured with quantitative computed tomography (QCT) |
| Change in UD iBMD | baseline and 12 months | 12-month change in ultra-distal integral volumetric bone mineral density, measured with quantitative computed tomography (QCT) |
| Change in UD cBMD | baseline and 12 months | 12-month change in ultra-distal cortical volumetric bone mineral density, measured with quantitative computed tomography (QCT) |
| Change in UD ecBMD | baseline and 12 months | 12-month change in ultra-distal endocortical bone mineral density, measured with quantitative computed tomography (QCT) |
| Change in UD tBMD | baseline and 12 months | 12-month change in ultra-distal trabecular bone mineral density, measured with quantitative computed tomography (QCT) |
| Change in UD cBMC | baseline and 12 months | 12-month change in ultra-distal cortical bone mineral content, measured with quantitative computed tomography (QCT) |
| Change in UD cBV | baseline and 12 months | 12-month change in ultra-distal cortical bone volume, measured with quantitative computed tomography (QCT) |
| Change in UD ecBV | baseline and 12 months | 12-month change in ultra-distal cortical bone volume, measured with quantitative computed tomography (QCT) |
| Change in UD tBV | baseline and 12 months | 12-month change in ultra-distal trabecular bone volume, measured with quantitative computed tomography (QCT) |
| Change in Cortical Thickness | measurements repeated at 0, 3, 6, 9, 12, 18, and 24 months from enrollment | Changes in cortical thickness at 3-month intervals, measured with high resolution peripheral quantitative computed tomography (HRpQCT) |
| Change in Trabecular BV/TV | measurements repeated at 0, 3, 6, 9, and 12 months from enrollment | trabecular bone volume fraction expressed as the ratio of bone volume (BV) to total volume (TV) using: (BV/TV). This quantity is measured with high resolution peripheral quantitative computed tomography (HRpQCT). It is expressed as a ratio, ranging from 0 (none of the volume is occupied by bone) to 1 (all of the volume is occupied by bone). |
| Change in UD iBV | baseline and 12 months | 12-month change in ultra-distal integral bone volume, measured with quantitative computed tomography (QCT) |
Participant flow
Recruitment details
Recruitment Period: December 2013-June 2017 All participants were recruited at a single site (Worcester Polytechnic Institute) and the surrounding community via social media, posters, email newsletters, and word of mouth at nearby universities, hospitals, and community events.
Participants by arm
| Arm | Count |
|---|---|
| Low Magnitude voluntary forearm compression by leaning onto the palm of the hand with low target strain
voluntary forearm loading task: voluntary task, consisting of leaning onto the palm of the hand until a target force is reached. Each loading bout consists of 100 loading cycles, which takes approximately 2 minutes to complete. The task is performed 4 times per week during the intervention period. | 21 |
| High Magnitude voluntary forearm compression by leaning onto the palm of the hand with high target strain
voluntary forearm loading task: voluntary task, consisting of leaning onto the palm of the hand until a target force is reached. Each loading bout consists of 100 loading cycles, which takes approximately 2 minutes to complete. The task is performed 4 times per week during the intervention period. | 24 |
| Low Rate voluntary forearm compression by leaning onto the palm of the hand with low strain rate (task performed slowly and evenly)
voluntary forearm loading task: voluntary task, consisting of leaning onto the palm of the hand until a target force is reached. Each loading bout consists of 100 loading cycles, which takes approximately 2 minutes to complete. The task is performed 4 times per week during the intervention period. | 21 |
| High Rate voluntary forearm compression by leaning onto the palm of the hand with high strain rate (task performed as quickly as possible, with a bump)
voluntary forearm loading task: voluntary task, consisting of leaning onto the palm of the hand until a target force is reached. Each loading bout consists of 100 loading cycles, which takes approximately 2 minutes to complete. The task is performed 4 times per week during the intervention period. | 20 |
| Control observation only | 16 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 8 | 7 | 8 | 9 | 1 |
| Overall Study | Pregnancy | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Control | Low Magnitude | High Magnitude | High Rate | Low Rate |
|---|---|---|---|---|---|---|
| Age, Continuous | 28.4 years STANDARD_DEVIATION 5.6 | 28.2 years STANDARD_DEVIATION 5.3 | 30.3 years STANDARD_DEVIATION 5.5 | 29.3 years STANDARD_DEVIATION 6.3 | 27.1 years STANDARD_DEVIATION 5.4 | 27.2 years STANDARD_DEVIATION 5.1 |
| Body Mass | 64.3 kg STANDARD_DEVIATION 8.7 | 65.0 kg STANDARD_DEVIATION 8.9 | 65.2 kg STANDARD_DEVIATION 8.8 | 61.0 kg STANDARD_DEVIATION 5.9 | 65.4 kg STANDARD_DEVIATION 10 | 65.4 kg STANDARD_DEVIATION 9.8 |
| Cortical Thickness | 0.784 mm STANDARD_DEVIATION 0.144 | 0.724 mm STANDARD_DEVIATION 0.085 | 0.811 mm STANDARD_DEVIATION 0.168 | 0.753 mm STANDARD_DEVIATION 0.162 | 0.828 mm STANDARD_DEVIATION 0.11 | 0.795 mm STANDARD_DEVIATION 0.154 |
| DXA Total Forearm T-score | -0.087 t-score STANDARD_DEVIATION 0.7 | -0.162 t-score STANDARD_DEVIATION 0.67 | 0.138 t-score STANDARD_DEVIATION 0.76 | -0.187 t-score STANDARD_DEVIATION 0.63 | -0.175 t-score STANDARD_DEVIATION 0.74 | 0.138 t-score STANDARD_DEVIATION 0.76 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 2 Participants | 2 Participants | 5 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 89 Participants | 14 Participants | 19 Participants | 18 Participants | 18 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Height | 164.8 cm STANDARD_DEVIATION 6.4 | 167.3 cm STANDARD_DEVIATION 7.6 | 165.8 cm STANDARD_DEVIATION 6.1 | 161.9 cm STANDARD_DEVIATION 6.1 | 164.9 cm STANDARD_DEVIATION 5.7 | 165.0 cm STANDARD_DEVIATION 6.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 0 Participants | 3 Participants | 2 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 76 Participants | 13 Participants | 16 Participants | 17 Participants | 14 Participants | 16 Participants |
| Region of Enrollment United States | 102 participants | 16 participants | 21 participants | 24 participants | 20 participants | 21 participants |
| Serum Vitamin D | 31.7 ng/mL STANDARD_DEVIATION 9.5 | 33.2 ng/mL STANDARD_DEVIATION 7.5 | 33.7 ng/mL STANDARD_DEVIATION 9.9 | 31.5 ng/mL STANDARD_DEVIATION 8.9 | 29.1 ng/mL STANDARD_DEVIATION 7.8 | 31.1 ng/mL STANDARD_DEVIATION 12.2 |
| Sex: Female, Male Female | 102 Participants | 16 Participants | 21 Participants | 24 Participants | 20 Participants | 21 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Total Forearm aBMD | 0.574 g/cm^2 STANDARD_DEVIATION 0.04 | 0.570 g/cm^2 STANDARD_DEVIATION 0.04 | 0.586 g/cm^2 STANDARD_DEVIATION 0.04 | 0.568 g/cm^2 STANDARD_DEVIATION 0.03 | 0.569 g/cm^2 STANDARD_DEVIATION 0.04 | 0.576 g/cm^2 STANDARD_DEVIATION 0.04 |
| Trabecular BV/TV | 0.135 ratio STANDARD_DEVIATION 0.026 | 0.141 ratio STANDARD_DEVIATION 0.03 | 0.131 ratio STANDARD_DEVIATION 0.024 | 0.135 ratio STANDARD_DEVIATION 0.026 | 0.130 ratio STANDARD_DEVIATION 0.024 | 0.138 ratio STANDARD_DEVIATION 0.026 |
| Ultradistal cBMC All Enrolled Participants | 0.380 g STANDARD_DEVIATION 0.122 | 0.356 g STANDARD_DEVIATION 0.077 | 0.432 g STANDARD_DEVIATION 0.163 | 0.380 g STANDARD_DEVIATION 0.123 | 0.354 g STANDARD_DEVIATION 0.104 | 0.369 g STANDARD_DEVIATION 0.109 |
| Ultradistal cBMC Subset of Participants who were also Analyzed at Follow-Up (12 months) | 0.383 g STANDARD_DEVIATION 0.128 | 0.369 g STANDARD_DEVIATION 0.076 | 0.457 g STANDARD_DEVIATION 0.177 | 0.351 g STANDARD_DEVIATION 0.117 | 0.369 g STANDARD_DEVIATION 0.104 | 0.377 g STANDARD_DEVIATION 0.132 |
| Ultradistal cBMD All Enrolled Participants | 0.473 g/cm^3 STANDARD_DEVIATION 0.028 | 0.468 g/cm^3 STANDARD_DEVIATION 0.014 | 0.486 g/cm^3 STANDARD_DEVIATION 0.035 | 0.471 g/cm^3 STANDARD_DEVIATION 0.029 | 0.473 g/cm^3 STANDARD_DEVIATION 0.027 | 0.465 g/cm^3 STANDARD_DEVIATION 0.028 |
| Ultradistal cBMD Subset of Participants who were also Analyzed at Follow-Up (12 months) | 0.471 g/cm^3 STANDARD_DEVIATION 0.029 | 0.471 g/cm^3 STANDARD_DEVIATION 0.013 | 0.485 g/cm^3 STANDARD_DEVIATION 0.039 | 0.469 g/cm^3 STANDARD_DEVIATION 0.033 | 0.470 g/cm^3 STANDARD_DEVIATION 0.023 | 0.462 g/cm^3 STANDARD_DEVIATION 0.029 |
| Ultradistal cBV All Enrolled Participants | 0.79 cm^3 STANDARD_DEVIATION 0.21 | 0.76 cm^3 STANDARD_DEVIATION 0.15 | 0.88 cm^3 STANDARD_DEVIATION 0.26 | 0.80 cm^3 STANDARD_DEVIATION 0.22 | 0.74 cm^3 STANDARD_DEVIATION 0.2 | 0.79 cm^3 STANDARD_DEVIATION 0.2 |
| Ultradistal cBV Subset of Participants who were also Analyzed at Follow-Up (12 months) | 0.80 cm^3 STANDARD_DEVIATION 0.22 | 0.78 cm^3 STANDARD_DEVIATION 0.14 | 0.92 cm^3 STANDARD_DEVIATION 0.26 | 0.74 cm^3 STANDARD_DEVIATION 0.2 | 0.78 cm^3 STANDARD_DEVIATION 0.21 | 0.81 cm^3 STANDARD_DEVIATION 0.25 |
| Ultradistal ecBMC All Enrolled Participants | 0.617 g STANDARD_DEVIATION 0.18 | 0.597 g STANDARD_DEVIATION 0.127 | 0.692 g STANDARD_DEVIATION 0.226 | 0.607 g STANDARD_DEVIATION 0.181 | 0.564 g STANDARD_DEVIATION 0.171 | 0.617 g STANDARD_DEVIATION 0.163 |
| Ultradistal ecBMC Subset of Participants who were also Analyzed at Follow-Up (12 months) | 0.627 g STANDARD_DEVIATION 0.18 | 0.613 g STANDARD_DEVIATION 0.135 | 0.745 g STANDARD_DEVIATION 0.211 | 0.556 g STANDARD_DEVIATION 0.149 | 0.596 g STANDARD_DEVIATION 0.172 | 0.644 g STANDARD_DEVIATION 0.195 |
| Ultradistal ecBMD All Enrolled Participants | 0.310 g/cm^3 STANDARD_DEVIATION 0.077 | 0.305 g/cm^3 STANDARD_DEVIATION 0.059 | 0.339 g/cm^3 STANDARD_DEVIATION 0.097 | 0.307 g/cm^3 STANDARD_DEVIATION 0.075 | 0.289 g/cm^3 STANDARD_DEVIATION 0.075 | 0.310 g/cm^3 STANDARD_DEVIATION 0.067 |
| Ultradistal ecBMD Subset of Participants who were also Analyzed at Follow-Up (12 months) | 0.312 g/cm^3 STANDARD_DEVIATION 0.076 | 0.309 g/cm^3 STANDARD_DEVIATION 0.063 | 0.358 g/cm^3 STANDARD_DEVIATION 0.092 | 0.286 g/cm^3 STANDARD_DEVIATION 0.064 | 0.301 g/cm^3 STANDARD_DEVIATION 0.069 | 0.315 g/cm^3 STANDARD_DEVIATION 0.08 |
| Ultradistal ecBV All Enrolled Participants | 1.97 cm^3 STANDARD_DEVIATION 0.16 | 1.96 cm^3 STANDARD_DEVIATION 0.11 | 2.02 cm^3 STANDARD_DEVIATION 0.15 | 1.96 cm^3 STANDARD_DEVIATION 0.14 | 1.93 cm^3 STANDARD_DEVIATION 0.19 | 1.98 cm^3 STANDARD_DEVIATION 0.18 |
| Ultradistal ecBV Subset of Participants who were also Analyzed at Follow-Up (12 months) | 1.99 cm^3 STANDARD_DEVIATION 0.15 | 1.98 cm^3 STANDARD_DEVIATION 0.09 | 2.08 cm^3 STANDARD_DEVIATION 0.12 | 1.93 cm^3 STANDARD_DEVIATION 0.12 | 1.96 cm^3 STANDARD_DEVIATION 0.21 | 2.02 cm^3 STANDARD_DEVIATION 0.15 |
| Ultradistal iBMC All Enrolled Participants | 0.890 g STANDARD_DEVIATION 0.151 | 0.883 g STANDARD_DEVIATION 0.116 | 0.940 g STANDARD_DEVIATION 0.179 | 0.886 g STANDARD_DEVIATION 0.149 | 0.844 g STANDARD_DEVIATION 0.155 | 0.894 g STANDARD_DEVIATION 0.141 |
| Ultradistal iBMC Subset of Participants who were also Analyzed at Follow-Up (12 months) | 0.906 g STANDARD_DEVIATION 0.145 | 0.898 g STANDARD_DEVIATION 0.124 | 0.997 g STANDARD_DEVIATION 0.143 | 0.849 g STANDARD_DEVIATION 0.134 | 0.875 g STANDARD_DEVIATION 0.14 | 0.926 g STANDARD_DEVIATION 0.16 |
| Ultradistal iBMD All Enrolled Participants | 0.236 g/cm^3 STANDARD_DEVIATION 0.035 | 0.234 g/cm^3 STANDARD_DEVIATION 0.031 | 0.243 g/cm^3 STANDARD_DEVIATION 0.044 | 0.238 g/cm^3 STANDARD_DEVIATION 0.035 | 0.228 g/cm^3 STANDARD_DEVIATION 0.033 | 0.237 g/cm^3 STANDARD_DEVIATION 0.03 |
| Ultradistal iBMD Subset of Participants who were also Analyzed at Follow-Up (12 months) | 0.237 g/cm^3 STANDARD_DEVIATION 0.034 | 0.233 g/cm^3 STANDARD_DEVIATION 0.029 | 0.250 g/cm^3 STANDARD_DEVIATION 0.044 | 0.230 g/cm^3 STANDARD_DEVIATION 0.033 | 0.233 g/cm^3 STANDARD_DEVIATION 0.029 | 0.239 g/cm^3 STANDARD_DEVIATION 0.032 |
| Ultradistal iBV All Enrolled Participants | 3.78 cm^3 STANDARD_DEVIATION 0.43 | 3.79 cm^3 STANDARD_DEVIATION 0.37 | 3.88 cm^3 STANDARD_DEVIATION 0.44 | 3.73 cm^3 STANDARD_DEVIATION 0.34 | 3.72 cm^3 STANDARD_DEVIATION 0.53 | 3.78 cm^3 STANDARD_DEVIATION 0.45 |
| Ultradistal iBV Subset of Participants who were also Analyzed at Follow-up (12 months) | 3.84 cm^3 STANDARD_DEVIATION 0.4 | 3.85 cm^3 STANDARD_DEVIATION 0.28 | 4.02 cm^3 STANDARD_DEVIATION 0.39 | 3.70 cm^3 STANDARD_DEVIATION 0.34 | 3.77 cm^3 STANDARD_DEVIATION 0.56 | 3.88 cm^3 STANDARD_DEVIATION 0.38 |
| Ultradistal tBMC All Enrolled Participants | 0.175 g STANDARD_DEVIATION 0.056 | 0.179 g STANDARD_DEVIATION 0.052 | 0.182 g STANDARD_DEVIATION 0.061 | 0.177 g STANDARD_DEVIATION 0.053 | 0.158 g STANDARD_DEVIATION 0.061 | 0.181 g STANDARD_DEVIATION 0.053 |
| Ultradistal tBMC Subset of Participants who were also Analyzed at Follow-Up (12 months) | 0.182 g STANDARD_DEVIATION 0.051 | 0.184 g STANDARD_DEVIATION 0.057 | 0.201 g STANDARD_DEVIATION 0.039 | 0.166 g STANDARD_DEVIATION 0.048 | 0.170 g STANDARD_DEVIATION 0.047 | 0.196 g STANDARD_DEVIATION 0.062 |
| Ultradistal tBMD All Enrolled Participants | 0.124 g/cm^3 STANDARD_DEVIATION 0.031 | 0.127 g/cm^3 STANDARD_DEVIATION 0.035 | 0.122 g/cm^3 STANDARD_DEVIATION 0.033 | 0.128 g/cm^3 STANDARD_DEVIATION 0.031 | 0.112 g/cm^3 STANDARD_DEVIATION 0.031 | 0.129 g/cm^3 STANDARD_DEVIATION 0.024 |
| Ultradistal tBMD Subset of Participants who were also Analyzed at Follow-Up (12 months) | 0.126 g/cm^3 STANDARD_DEVIATION 0.027 | 0.125 g/cm^3 STANDARD_DEVIATION 0.033 | 0.131 g/cm^3 STANDARD_DEVIATION 0.022 | 0.121 g/cm^3 STANDARD_DEVIATION 0.028 | 0.120 g/cm^3 STANDARD_DEVIATION 0.026 | 0.133 g/cm^3 STANDARD_DEVIATION 0.027 |
| Ultradistal tBV All Enrolled Participants | 1.41 cm^3 STANDARD_DEVIATION 0.27 | 1.42 cm^3 STANDARD_DEVIATION 0.27 | 1.47 cm^3 STANDARD_DEVIATION 0.3 | 1.39 cm^3 STANDARD_DEVIATION 0.23 | 1.38 cm^3 STANDARD_DEVIATION 0.31 | 1.41 cm^3 STANDARD_DEVIATION 0.26 |
| Ultradistal tBV Subset of Participants who were also Analyzed at Follow-Up (12 months) | 1.45 cm^3 STANDARD_DEVIATION 0.26 | 1.46 cm^3 STANDARD_DEVIATION 0.22 | 1.55 cm^3 STANDARD_DEVIATION 0.3 | 1.38 cm^3 STANDARD_DEVIATION 0.24 | 1.42 cm^3 STANDARD_DEVIATION 0.32 | 1.45 cm^3 STANDARD_DEVIATION 0.24 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 24 | 0 / 21 | 0 / 20 | 0 / 16 |
| other Total, other adverse events | 8 / 21 | 11 / 24 | 10 / 21 | 11 / 20 | 7 / 16 |
| serious Total, serious adverse events | 0 / 21 | 0 / 24 | 0 / 21 | 0 / 20 | 0 / 16 |
Outcome results
Primary
Change in UD iBMC
12-month change in ultra-distal integral bone mineral content, measured with quantitative computed tomography (QCT)
Time frame: baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Magnitude | Change in UD iBMC | 0.0049 g | Standard Deviation 0.0146 |
| High Magnitude | Change in UD iBMC | -0.0020 g | Standard Deviation 0.0165 |
| Low Rate | Change in UD iBMC | 0.0252 g | Standard Deviation 0.0206 |
| High Rate | Change in UD iBMC | 0.0309 g | Standard Deviation 0.0211 |
| Control | Change in UD iBMC | -0.0106 g | Standard Deviation 0.0241 |
Comparison: The power analysis for the overall study was based on 12-month change in UD iBMC. The power calculation, based on pilot data, determined that 20 participants per group would have 80% power to detect a 1.0±1.1% change.~The null hypothesis was that change in UD iBMC was not proportional to strain magnitude. Raw change in iBMC was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.119Regression, Linear
Comparison: The null hypothesis was that change in UD iBMC was not proportional to strain rate. Raw change in iBMC was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: <0.01Regression, Linear
Secondary
Change in Cortical Thickness
Changes in cortical thickness at 3-month intervals, measured with high resolution peripheral quantitative computed tomography (HRpQCT)
Time frame: measurements repeated at 0, 3, 6, 9, 12, 18, and 24 months from enrollment
Population: Analysis population includes participants analyzed at at least one interim timepoint. Exact values are provided for individual timepoints below.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Magnitude | Change in Cortical Thickness | 3 months | 0.001 mm | Standard Deviation 0.018 |
| Low Magnitude | Change in Cortical Thickness | 6 months | -0.003 mm | Standard Deviation 0.037 |
| Low Magnitude | Change in Cortical Thickness | 9 months | 0.001 mm | Standard Deviation 0.015 |
| Low Magnitude | Change in Cortical Thickness | 12 months | -0.009 mm | Standard Deviation 0.027 |
| High Magnitude | Change in Cortical Thickness | 3 months | -0.012 mm | Standard Deviation 0.056 |
| High Magnitude | Change in Cortical Thickness | 12 months | -0.002 mm | Standard Deviation 0.027 |
| High Magnitude | Change in Cortical Thickness | 6 months | 0.002 mm | Standard Deviation 0.021 |
| High Magnitude | Change in Cortical Thickness | 9 months | -0.012 mm | Standard Deviation 0.064 |
| Low Rate | Change in Cortical Thickness | 12 months | 0.015 mm | Standard Deviation 0.018 |
| Low Rate | Change in Cortical Thickness | 6 months | 0.008 mm | Standard Deviation 0.025 |
| Low Rate | Change in Cortical Thickness | 9 months | 0.006 mm | Standard Deviation 0.019 |
| Low Rate | Change in Cortical Thickness | 3 months | 0.009 mm | Standard Deviation 0.03 |
| High Rate | Change in Cortical Thickness | 3 months | 0.032 mm | Standard Deviation 0.031 |
| High Rate | Change in Cortical Thickness | 6 months | 0.005 mm | Standard Deviation 0.025 |
| High Rate | Change in Cortical Thickness | 12 months | 0.004 mm | Standard Deviation 0.029 |
| High Rate | Change in Cortical Thickness | 9 months | -0.007 mm | Standard Deviation 0.022 |
| Control | Change in Cortical Thickness | 12 months | 0.002 mm | Standard Deviation 0.022 |
| Control | Change in Cortical Thickness | 9 months | -0.002 mm | Standard Deviation 0.021 |
| Control | Change in Cortical Thickness | 6 months | 0.004 mm | Standard Deviation 0.018 |
| Control | Change in Cortical Thickness | 3 months | -0.004 mm | Standard Deviation 0.018 |
Comparison: The null hypothesis was that change in cortical thickness was not proportional to strain magnitude. At each time point, raw change relative to baseline was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.
Comparison: The null hypothesis was that change in cortical thickness was not proportional to strain rate. At each time point, raw change relative to baseline was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.
Secondary
Change in Trabecular BV/TV
trabecular bone volume fraction expressed as the ratio of bone volume (BV) to total volume (TV) using: (BV/TV). This quantity is measured with high resolution peripheral quantitative computed tomography (HRpQCT). It is expressed as a ratio, ranging from 0 (none of the volume is occupied by bone) to 1 (all of the volume is occupied by bone).
Time frame: measurements repeated at 0, 3, 6, 9, and 12 months from enrollment
Population: Analysis population includes participants analyzed at at least one interim timepoint. Exact values are provided for individual timepoints below.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Magnitude | Change in Trabecular BV/TV | 3 months | -0.0006 ratio | Standard Deviation 0.0023 |
| Low Magnitude | Change in Trabecular BV/TV | 6 months | 0.0006 ratio | Standard Deviation 0.003 |
| Low Magnitude | Change in Trabecular BV/TV | 9 months | 0.0014 ratio | Standard Deviation 0.002 |
| Low Magnitude | Change in Trabecular BV/TV | 12 months | 0.0002 ratio | Standard Deviation 0.0026 |
| High Magnitude | Change in Trabecular BV/TV | 3 months | 0.0003 ratio | Standard Deviation 0.003 |
| High Magnitude | Change in Trabecular BV/TV | 12 months | 0.0010 ratio | Standard Deviation 0.0033 |
| High Magnitude | Change in Trabecular BV/TV | 6 months | -0.0004 ratio | Standard Deviation 0.0031 |
| High Magnitude | Change in Trabecular BV/TV | 9 months | -0.0004 ratio | Standard Deviation 0.0027 |
| Low Rate | Change in Trabecular BV/TV | 12 months | 0.0009 ratio | Standard Deviation 0.0032 |
| Low Rate | Change in Trabecular BV/TV | 6 months | 0.0011 ratio | Standard Deviation 0.0027 |
| Low Rate | Change in Trabecular BV/TV | 9 months | 0.0003 ratio | Standard Deviation 0.003 |
| Low Rate | Change in Trabecular BV/TV | 3 months | -0.0020 ratio | Standard Deviation 0.0044 |
| High Rate | Change in Trabecular BV/TV | 3 months | 0.0002 ratio | Standard Deviation 0.0025 |
| High Rate | Change in Trabecular BV/TV | 6 months | 0.0008 ratio | Standard Deviation 0.003 |
| High Rate | Change in Trabecular BV/TV | 12 months | 0.0007 ratio | Standard Deviation 0.0034 |
| High Rate | Change in Trabecular BV/TV | 9 months | -0.0001 ratio | Standard Deviation 0.0034 |
| Control | Change in Trabecular BV/TV | 12 months | 0.000 ratio | Standard Deviation 0.0048 |
| Control | Change in Trabecular BV/TV | 9 months | -0.0020 ratio | Standard Deviation 0.0028 |
| Control | Change in Trabecular BV/TV | 6 months | -0.0007 ratio | Standard Deviation 0.0032 |
| Control | Change in Trabecular BV/TV | 3 months | -0.0014 ratio | Standard Deviation 0.0021 |
Comparison: The null hypothesis was that change in bone volume fraction (BV/TV) was not proportional to strain magnitude. At each time point, raw change relative to baseline was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.
Comparison: The null hypothesis was that change in bone volume fraction (BV/TV) was not proportional to strain rate. At each time point, raw change relative to baseline was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: >0.05Regression, Linear
Secondary
Change in UD cBMC
12-month change in ultra-distal cortical bone mineral content, measured with quantitative computed tomography (QCT)
Time frame: baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Magnitude | Change in UD cBMC | 0.0037 g | Standard Deviation 0.0127 |
| High Magnitude | Change in UD cBMC | -0.0001 g | Standard Deviation 0.0101 |
| Low Rate | Change in UD cBMC | 0.0139 g | Standard Deviation 0.0124 |
| High Rate | Change in UD cBMC | 0.0166 g | Standard Deviation 0.0176 |
| Control | Change in UD cBMC | 0.0024 g | Standard Deviation 0.0243 |
Comparison: The null hypothesis was that change in UD cBMC was not proportional to strain magnitude. Raw change in cBMC was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.809Regression, Linear
Comparison: The null hypothesis was that change in UD cBMC was not proportional to strain rate. Raw change in cBMC was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.155Regression, Linear
Secondary
Change in UD cBMD
12-month change in ultra-distal cortical volumetric bone mineral density, measured with quantitative computed tomography (QCT)
Time frame: baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Magnitude | Change in UD cBMD | -0.0025 g/cm^3 | Standard Deviation 0.0068 |
| High Magnitude | Change in UD cBMD | -0.0015 g/cm^3 | Standard Deviation 0.0073 |
| Low Rate | Change in UD cBMD | 0.0073 g/cm^3 | Standard Deviation 0.0058 |
| High Rate | Change in UD cBMD | 0.0036 g/cm^3 | Standard Deviation 0.0081 |
| Control | Change in UD cBMD | 0.0029 g/cm^3 | Standard Deviation 0.0101 |
Comparison: The null hypothesis was that change in UD cBMD was not proportional to strain magnitude. Raw change in cBMD was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.202Regression, Linear
Comparison: The null hypothesis was that change in UD cBMD was not proportional to strain rate. Raw change in cBMD was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.381Regression, Linear
Secondary
Change in UD cBV
12-month change in ultra-distal cortical bone volume, measured with quantitative computed tomography (QCT)
Time frame: baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Magnitude | Change in UD cBV | 0.014 cm^3 | Standard Deviation 0.028 |
| High Magnitude | Change in UD cBV | 0.003 cm^3 | Standard Deviation 0.028 |
| Low Rate | Change in UD cBV | 0.016 cm^3 | Standard Deviation 0.035 |
| High Rate | Change in UD cBV | 0.031 cm^3 | Standard Deviation 0.038 |
| Control | Change in UD cBV | 0.002 cm^3 | Standard Deviation 0.056 |
Comparison: The null hypothesis was that change in UD cBV was not proportional to strain magnitude. Raw change in cBV was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.676Regression, Linear
Comparison: The null hypothesis was that change in UD cBV was not proportional to strain rate. Raw change in cBV was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.289Regression, Linear
Secondary
Change in UD ecBMC
12-month change in ultra-distal endocortical bone mineral content, measured with quantitative computed tomography (QCT)
Time frame: baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Magnitude | Change in UD ecBMC | 0.0007 g | Standard Deviation 0.0173 |
| High Magnitude | Change in UD ecBMC | 0.0001 g | Standard Deviation 0.0151 |
| Low Rate | Change in UD ecBMC | 0.0286 g | Standard Deviation 0.024 |
| High Rate | Change in UD ecBMC | 0.0287 g | Standard Deviation 0.0274 |
| Control | Change in UD ecBMC | -0.0004 g | Standard Deviation 0.0311 |
Comparison: The null hypothesis was that change in UD ecBMC was not proportional to strain magnitude. Raw change in ecBMC was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.991Regression, Linear
Comparison: The null hypothesis was that change in UD ecBMC was not proportional to strain rate. Raw change in ecBMC was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.018Regression, Linear
Secondary
Change in UD ecBMD
12-month change in ultra-distal endocortical bone mineral density, measured with quantitative computed tomography (QCT)
Time frame: baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Magnitude | Change in UD ecBMD | -0.0031 g/cm^3 | Standard Deviation 0.0102 |
| High Magnitude | Change in UD ecBMD | -0.0012 g/cm^3 | Standard Deviation 0.008 |
| Low Rate | Change in UD ecBMD | 0.0141 g/cm^3 | Standard Deviation 0.0105 |
| High Rate | Change in UD ecBMD | 0.0122 g/cm^3 | Standard Deviation 0.0116 |
| Control | Change in UD ecBMD | 0.0005 g/cm^3 | Standard Deviation 0.0141 |
Comparison: The null hypothesis was that change in UD ecBMD was not proportional to strain magnitude. Raw change in ecBMD was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.697Regression, Linear
Comparison: The null hypothesis was that change in UD ecBMD was not proportional to strain rate. Raw change in ecBMD was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.018Regression, Linear
Secondary
Change in UD ecBV
12-month change in ultra-distal cortical bone volume, measured with quantitative computed tomography (QCT)
Time frame: baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Magnitude | Change in UD ecBV | 0.018 cm^3 | Standard Deviation 0.029 |
| High Magnitude | Change in UD ecBV | 0.008 cm^3 | Standard Deviation 0.03 |
| Low Rate | Change in UD ecBV | -0.0003 cm^3 | Standard Deviation 0.025 |
| High Rate | Change in UD ecBV | 0.009 cm^3 | Standard Deviation 0.028 |
| Control | Change in UD ecBV | -0.007 cm^3 | Standard Deviation 0.03 |
Comparison: The null hypothesis was that change in UD ecBV was not proportional to strain magnitude. Raw change in ecBV was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.096Regression, Linear
Comparison: The null hypothesis was that change in UD ecBV was not proportional to strain rate. Raw change in ecBV was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.344Regression, Linear
Secondary
Change in UD iBMD
12-month change in ultra-distal integral volumetric bone mineral density, measured with quantitative computed tomography (QCT)
Time frame: baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Magnitude | Change in UD iBMD | -0.0008 g/cm^3 | Standard Deviation 0.0024 |
| High Magnitude | Change in UD iBMD | -0.0007 g/cm^3 | Standard Deviation 0.0027 |
| Low Rate | Change in UD iBMD | 0.0072 g/cm^3 | Standard Deviation 0.0027 |
| High Rate | Change in UD iBMD | 0.0071 g/cm^3 | Standard Deviation 0.0035 |
| Control | Change in UD iBMD | -0.0014 g/cm^3 | Standard Deviation 0.0047 |
Comparison: The null hypothesis was that change in UD iBMD was not proportional to strain magnitude. Raw change in iBMD was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.84Regression, Linear
Comparison: The null hypothesis was that change in UD iBMD was not proportional to strain rate. Raw change in iBMD was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: <0.001Regression, Linear
Secondary
Change in UD iBV
12-month change in ultra-distal integral bone volume, measured with quantitative computed tomography (QCT)
Time frame: baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Magnitude | Change in UD iBV | 0.027 cm^3 | Standard Deviation 0.061 |
| High Magnitude | Change in UD iBV | 0.003 cm^3 | Standard Deviation 0.055 |
| Low Rate | Change in UD iBV | -0.011 cm^3 | Standard Deviation 0.049 |
| High Rate | Change in UD iBV | 0.012 cm^3 | Standard Deviation 0.066 |
| Control | Change in UD iBV | -0.026 cm^3 | Standard Deviation 0.068 |
Comparison: The null hypothesis was that change in UD iBV was not proportional to strain magnitude. Raw change in iBV was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.101Regression, Linear
Comparison: The null hypothesis was that change in UD iBV was not proportional to strain rate. Raw change in iBV was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.344Regression, Linear
Secondary
Change in UD tBMC
12-month change in ultra-distal trabecular bone mineral content, measured with quantitative computed tomography (QCT)
Time frame: baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Magnitude | Change in UD tBMC | 0.0018 g | Standard Deviation 0.0082 |
| High Magnitude | Change in UD tBMC | -0.0021 g | Standard Deviation 0.0067 |
| Low Rate | Change in UD tBMC | 0.0072 g | Standard Deviation 0.0092 |
| High Rate | Change in UD tBMC | 0.0112 g | Standard Deviation 0.0106 |
| Control | Change in UD tBMC | -0.0048 g | Standard Deviation 0.0107 |
Comparison: The null hypothesis was that change in UD tBMC was not proportional to strain magnitude. Raw change in tBMC was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.153Regression, Linear
Comparison: The null hypothesis was that change in UD tBMC was not proportional to strain rate. Raw change in tBMC was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.001Regression, Linear
Secondary
Change in UD tBMD
12-month change in ultra-distal trabecular bone mineral density, measured with quantitative computed tomography (QCT)
Time frame: baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Magnitude | Change in UD tBMD | 0.0006 g/cm^3 | Standard Deviation 0.0028 |
| High Magnitude | Change in UD tBMD | -0.0013 g/cm^3 | Standard Deviation 0.0036 |
| Low Rate | Change in UD tBMD | 0.0050 g/cm^3 | Standard Deviation 0.0043 |
| High Rate | Change in UD tBMD | 0.0071 g/cm^3 | Standard Deviation 0.0053 |
| Control | Change in UD tBMD | -0.0029 g/cm^3 | Standard Deviation 0.0046 |
Comparison: The null hypothesis was that change in UD tBMD was not proportional to strain magnitude. Raw change in tBMD was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.073Regression, Linear
Comparison: The null hypothesis was that change in UD tBMD was not proportional to strain rate. Raw change in tBMD was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: <0.001Regression, Linear
Secondary
Change in UD tBV
12-month change in ultra-distal trabecular bone volume, measured with quantitative computed tomography (QCT)
Time frame: baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Magnitude | Change in UD tBV | 0.006 cm^3 | Standard Deviation 0.029 |
| High Magnitude | Change in UD tBV | -0.004 cm^3 | Standard Deviation 0.023 |
| Low Rate | Change in UD tBV | -0.003 cm^3 | Standard Deviation 0.023 |
| High Rate | Change in UD tBV | 0.006 cm^3 | Standard Deviation 0.034 |
| Control | Change in UD tBV | -0.011 cm^3 | Standard Deviation 0.033 |
Comparison: The null hypothesis was that change in UD tBV was not proportional to strain magnitude. Raw change in tBV was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.332Regression, Linear
Comparison: The null hypothesis was that change in UD tBV was not proportional to strain rate. Raw change in tBV was analyzed as the dependent variable in a linear regression model with coefficients representing contrasts between the two experimental groups and the control group.p-value: 0.399Regression, Linear