A Prospective Study of Human Bone Adaptation Using a Novel in Vivo Loading Model

Study Overview
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Brief Summary
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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
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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effect of withdrawing mechanical signals, by measuring bone structure during the 12 months after the intervention is withdrawn.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).

Official Title
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A Prospective Study of Human Bone Adaptation Using a Novel in Vivo Loading Model

Conditions
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Bone Loss

Intervention / Treatment
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* Other: voluntary forearm loading task


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Magnitude<br>voluntary forearm compression by leaning onto the palm of the hand with low target strain | Other: voluntary forearm loading task<br>* 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.<br>|
| Experimental: High Magnitude<br>voluntary forearm compression by leaning onto the palm of the hand with high target strain | Other: voluntary forearm loading task<br>* 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.<br>|
| Experimental: Low Rate<br>voluntary forearm compression by leaning onto the palm of the hand with low strain rate (task performed slowly and evenly) | Other: voluntary forearm loading task<br>* 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.<br>|
| Experimental: High Rate<br>voluntary forearm compression by leaning onto the palm of the hand with high strain rate (task performed as quickly as possible, with a bump) | Other: voluntary forearm loading task<br>* 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.<br>|
| No Intervention: Control<br>observation only | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in UD iBMC | 12-month change in ultra-distal integral bone mineral content, measured with quantitative computed tomography (QCT) | baseline and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in UD cBMC | 12-month change in ultra-distal cortical bone mineral content, measured with quantitative computed tomography (QCT) | baseline and 12 months | 
| Change in UD ecBMC | 12-month change in ultra-distal endocortical bone mineral content, measured with quantitative computed tomography (QCT) | baseline and 12 months | 
| Change in UD tBMC | 12-month change in ultra-distal trabecular bone mineral content, measured with quantitative computed tomography (QCT) | baseline and 12 months | 
| Change in UD iBMD | 12-month change in ultra-distal integral volumetric bone mineral density, measured with quantitative computed tomography (QCT) | baseline and 12 months | 
| Change in UD cBMD | 12-month change in ultra-distal cortical volumetric bone mineral density, measured with quantitative computed tomography (QCT) | baseline and 12 months | 
| Change in UD ecBMD | 12-month change in ultra-distal endocortical bone mineral density, measured with quantitative computed tomography (QCT) | baseline and 12 months | 
| Change in UD tBMD | 12-month change in ultra-distal trabecular bone mineral density, measured with quantitative computed tomography (QCT) | baseline and 12 months | 
| Change in UD iBV | 12-month change in ultra-distal integral bone volume, measured with quantitative computed tomography (QCT) | baseline and 12 months | 
| Change in UD cBV | 12-month change in ultra-distal cortical bone volume, measured with quantitative computed tomography (QCT) | baseline and 12 months | 
| Change in UD ecBV | 12-month change in ultra-distal cortical bone volume, measured with quantitative computed tomography (QCT) | baseline and 12 months | 
| Change in UD tBV | 12-month change in ultra-distal trabecular bone volume, measured with quantitative computed tomography (QCT) | baseline and 12 months | 
| Change in Cortical Thickness | Changes in cortical thickness at 3-month intervals, measured with high resolution peripheral quantitative computed tomography (HRpQCT) | measurements repeated at 0, 3, 6, 9, 12, 18, and 24 months from enrollment | 
| 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). | measurements repeated at 0, 3, 6, 9, and 12 months from enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bone, adaptation, mechanical stimuli, women, peak bone mass