Jump-In: Building Better Bones

Study Overview
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Brief Summary
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The Jump-In study will prospectively assess the effects of impact exercise on skeletal development in young girls, including bone mass, bone mineral density, and bone geometry. We hypothesize that girls who regularly participate in impact loading exercise will accrue greater skeletal mass, increase bone density and undergo structural adaptations that in combination will improve bone strength compared to girls who do not participate in impact exercise.

Detailed Description
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Jump-In is a school-based, block-randomized, trial of the effects of impact-loading exercise on skeletal development in prepubescent and early pubescent girls. Fourth (n= 200) and sixth (n= 200) grade girls in 14 Tucson (Arizona) schools with no contraindication to physical exercise will be enrolled. Girls in intervention schools will participate in impact activities 3 times per week at school, progressively increasing the number (up to 40) of jumps and their height (from 6 inches to 18 inches per repetition) over the initial 2 months. Thereafter, new activities will be introduced approximately every 2-3 months to maintain interest and motivation, and continually stress the skeleton in novel ways, over 2 years of intervention. Physical and behavioral assessments will be done in both intervention and control groups at baseline, end of the initial school year, and yearly thereafter for 5 years. Assessments include height and weight, selected skeletal lengths, fat, lean soft tissue, bone mineral content and areal density from dual energy x-ray absorptiometry (DXA), and bone geometry (e.g., cortical thickness, periosteal circumference and cortical and trabecular density) and muscle area from peripheral quantitative computed tomography (pQCT). Also, maturation will be assessed via the Tanner Stage (self-assessment against standardized drawings of stages of physical development), diet from the Harvard Youth Food Frequency Questionnaire, and physical activity using pedometers and standardized questionnaires. We hypothesize that girls in intervention schools will demonstrate enhanced skeletal development, including greater mineral mass and density, and enhanced bone geometry, leading to greater bone strength compared to girls in control schools. We further hypothesize that younger (Tanner Stage 1) girls will experience greater adaptations than older girls (Tanner 2 and 3), and that positive adaptations will be maintained throughout the 3-year follow-up period.

Official Title
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Exercise and Bone Development in Young Girls

Conditions
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Adolescent Development

Intervention / Treatment
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* Other: Skeletal loading


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: female; entering 4th or 6th grade at enrollment; and willing and able to undergo all of the testing requirements; no physical conditions that limit participation in physical activity/exercise; able to read and write English. Exclusion Criteria: Girls with severe learning disabilities (identified by schools), who are unable to complete questionnaires or otherwise comply with assessment protocols will be excluded. Any subjects (or potential subjects) suffering from medical conditions and/or disabilities that would limit their participation in exercise will be excluded from the study, following the American Academy of Pediatrics (AAP) guidelines. Further, any volunteers who are taking medications that would limit exercise and/or alter bone mineral accrual will also be excluded from the study. Girls with a positive pregnancy screening test at the time of the lab visit before DXA scanning will be excluded.

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 12 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise Intervention<br>Implementation of intervention program designed to provide skeletal loading through high impact activities. All activities performed by subjects in exercise intervention arm will be assessed by physical activity questionnaire and use of pedometer. Have baseline anthropometric measurements, total body DXA scans and peripheral quantitative computed tomography (pQCT) scans of the tibia and femur. | Other: Skeletal loading<br>* Impact activities, 3 times per week, increasing the number of jumps (up to 40) and increasing height (from 6 inches to 24 inches per repetition) over the initial 8-weeks (2 months). New activities will be introduced approximately every 2-3 months in order to continually stress the skeleton over 2 years.<br>|
| No Intervention: Control<br>Participants in this arm will not take part in exercise intervention. All activities performed by subjects in control arm will be assessed by physical activity questionnaire and use of pedometer. Have baseline anthropometric measurements, total body DXA scans and peripheral quantitative computed tomography (pQCT) scans of the tibia and femur. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Total Volumetric Bone Density at the Femur 4% Site | Baseline (initial) measurement of total volumetric bone density at the femur 4% site. Measurement made by peripheral quantitative computed tomography (pQCT) at a distance of 4% of total femur length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline | 
| Baseline Volumetric Bone Density of Trabecular Bone at the Femur 4% Site | Baseline (initial) measurement of volumetric bone density of trabecular bone at the femur 4% site . Measurement made by pQCT at a distance of 4% of total femur length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline | 
| Baseline Volumetric Bone Density of Cortical Bone at the Femur 4% Site | Baseline (initial) measurement of volumetric bone density of Cortical bone at the femur 4% site . Measurement made by pQCT at a distance of 4% of total femur length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline | 
| Baseline Trabecular Bone Area at the Femur 4% Site | Baseline (initial) measurement of trabecular bone area at the femur 4% site . Measurement made by pQCT at a distance of 4% of total femur length from the distal growth plate. Measurement units: square millimeters (mm^2). | Baseline | 
| Baseline Cortical Bone Area at the Femur 4% Site | Baseline (initial) measurement of cortical bone area at the femur 4% site . Measurement made by pQCT at a distance of 4% of total femur length from the distal growth plate. Measurement units: square millimeters (mm^2). | Baseline | 
| Baseline Periosteal Circumference at the Femur 4% Site | Baseline (initial) measurement of periosteal circumference at the femur 4% site . Measurement made by pQCT at a distance of 4% of total femur length from the distal growth plate. Measurement units: millimeters (mm). | Baseline | 
| Baseline Bone Strength Index at the Femur 4% Site | Baseline (initial) measurement of bone strength index (BSI) at the femur 4% site. Bone Strength Index (BSI) is a measurement of the resistance to compression forces at the epiphyses of long bones. Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: mm^4. | Baseline | 
| Baseline Total Volumetric Bone Density at the Femur 20% Site | Baseline (initial) measurement of total volumetric bone density at the femur 20% site . Measurement made by pQCT at a distance of 20% of total femur length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline | 
| Baseline Volumetric Bone Density of Trabecular Bone at the Femur 20% Site | Baseline (initial) measurement of volumetric bone density of trabecular bone at the femur 20% site . Measurement made by pQCT at a distance of 20% of total femur length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline | 
| Baseline Volumetric Bone Density of Cortical Bone at the Femur 20% Site | Baseline (initial) measurement of volumetric bone density of Cortical bone at the femur 20% site . Measurement made by pQCT at a distance of 20% of total femur length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline | 
| Baseline Periosteal Circumference at the Femur 20% Site | Baseline (initial) measurement of periosteal circumference at the femur 20% site . Measurement made by pQCT at a distance of 20% of total femur length from the distal growth plate. Measurement units: millimeters (mm). | Baseline | 
| Baseline Cortical Thickness at the Femur 20% Site | Baseline (initial) measurement of cortical thickness at the femur 20% site . Measurement made by pQCT at a distance of 20% of total femur length from the distal growth plate. Measurement units: millimeters (mm). | Baseline | 
| Baseline Stress-Strain Index at the Femur 20% Site | Baseline (initial) measurement of stress-strain index at the femur 20% site. Stress-strain index (also called strength-strain index and stress-strength index in the literature) is a measure of the resistance to torsional and bending forces at diaphyseal sites of long bones. Measurement made by pQCT at a distance of 20% of total femur length from the distal growth plate. Measurement units: mm^3. | Baseline | 
| Baseline Volumetric Bone Density of Trabecular Bone at the Tibia 4% Site | Baseline (initial) measurement of volumetric bone density of trabecular bone at the tibia 4% site . Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline | 
| Baseline Total Volumetric Bone Density at the Tibia 4% Site | Baseline (initial) measurement of total volumetric bone density at the tibia 4% site . Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline | 
| Baseline Volumetric Bone Density of Cortical Bone at the Tibia 4% Site | Baseline (initial) measurement of volumetric bone density of cortical bone at the tibia 4% site . Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline | 
| Baseline Trabecular Bone Area at the Tibia 4% Site | Baseline (initial) measurement of trabecular bone area at the tibia 4% site . Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: square millimeters (mm^2). | Baseline | 
| Baseline Cortical Bone Area at the Tibia 4% Site | Baseline (initial) measurement of cortical bone area at the tibia 4% site . Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: square millimeters (mm^2). | Baseline | 
| Baseline Periosteal Circumference at the Tibia 4% Site | Baseline (initial) measurement of periosteal circumference at the tibia 4% site . Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: millimeters (mm). | Baseline | 
| Baseline Bone Strength Index at the Tibia 4% Site | Baseline (initial) measurement of bone strength index (BSI) at the tibia 4% site. Bone Strength Index (BSI) is a measurement of the resistance to compression forces at the epiphyses of long bones. Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: mm^4. | Baseline | 
| Baseline Total Volumetric Bone Density at the Tibia 50% Site | Baseline (initial) measurement of total volumetric bone density at the tibia 50% site . Measurement made by pQCT at a distance of 50% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline | 
| Baseline Volumetric Bone Density of Trabecular Bone at the Tibia 50% Site | Baseline (initial) measurement of volumetric bone density of trabecular bone at the tibia 50% site . Measurement made by pQCT at a distance of 50% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline | 
| Baseline Volumetric Bone Density of Cortical Bone at the Tibia 50% Site | Baseline (initial) measurement of volumetric bone density of cortical bone at the tibia 50% site . Measurement made by pQCT at a distance of 50% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline | 
| Baseline Periosteal Circumference at the Tibia 50% Site | Baseline (initial) measurement of periosteal circumference at the tibia 50% site . Measurement made by pQCT at a distance of 50% of total tibia length from the distal growth plate. Measurement units: millimeters (mm). | Baseline | 
| Baseline Cortical Thickness at the Tibia 50% Site | Baseline (initial) measurement of cortical thickness at the tibia 50% site . Measurement made by pQCT at a distance of 50% of total tibia length from the distal growth plate. Measurement units: millimeters (mm). | Baseline | 
| Baseline Stress-Strain Index at the Tibia 50% Site | Baseline (initial) measurement of stress-strain index at the tibia 50% site. Stress-strain index (also called strength-strain index and stress-strength index in the literature) is a measure of the resistance to torsional and bending forces at diaphyseal sites of long bones. Measurement made by pQCT at a distance of 50% of total tibia length from the distal growth plate. Measurement units: mm^3. | Baseline | 
| Baseline Total Volumetric Bone Density at the Tibia 66% Site | Baseline (initial) measurement of total volumetric bone density at the tibia 66% site . Measurement made by pQCT at a distance of 66% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline | 
| Baseline Volumetric Bone Density of Trabecular Bone at the Tibia 66% Site | Baseline (initial) measurement of volumetric bone density of trabecular bone at the tibia 66% site . Measurement made by pQCT at a distance of 66% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline | 
| Baseline Volumetric Bone Density of Cortical Bone at the Tibia 66% Site | Baseline (initial) measurement of volumetric bone density of cortical bone at the tibia 66% site . Measurement made by pQCT at a distance of 66% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline | 
| Baseline Periosteal Circumference at the Tibia 66% Site | Baseline (initial) measurement of periosteal circumference at the tibia 66% site . Measurement made by pQCT at a distance of 66% of total tibia length from the distal growth plate. Measurement units: millimeters (mm). | Baseline | 
| Baseline Cortical Thickness at the Tibia 66% Site | Baseline (initial) measurement of cortical thickness at the tibia 66% site . Measurement made by pQCT at a distance of 66% of total tibia length from the distal growth plate. Measurement units: millimeters (mm). | Baseline | 
| Baseline Stress-Strain Index at the Tibia 66% Site | Baseline (initial) measurement of strength-strain index at the tibia 66% site. Stress-strain index (also called strength-strain index and stress-strength index in the literature) is a measure of the resistance to torsional and bending forces at diaphyseal sites of long bones. Measurement made by pQCT at a distance of 66% of total tibia length from the distal growth plate. Measurement units: mm^3. | Baseline | 
| 12-month Change in Total Volumetric Bone Density the Femur 4% Site | Baseline to 12-month change in total volumetric bone density at the femur 4% site . Measurement made by pQCT at a distance of 4% of total femur length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 12-months | 
| 12-month Change in Volumetric Bone Density of Trabecular Bone at the Femur 4% Site | Baseline to 12-month change in volumetric bone density of trabecular bone at the femur 4% site . Measurement made by pQCT at a distance of 4% of total femur length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 12-months | 
| 12-month Change in Volumetric Bone Density of Cortical Bone at the Femur 4% Site | Baseline to 12-month change in volumetric bone density of cortical bone at the femur 4% site . Measurement made by pQCT at a distance of 4% of total femur length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 12-months | 
| 12-month Change in Trabecular Bone Area at the Femur 4% Site | Baseline to 12-month change in trabecular bone area at the femur 4% site . Measurement made by pQCT at a distance of 4% of total femur length from the distal growth plate. Measurement units: square millimeters (mm^2). | Baseline to 12-months | 
| 12-month Change in Cortical Bone Area at the Femur 4% Site | Baseline to 12-month change in cortical bone area at the femur 4% site . Measurement made by pQCT at a distance of 4% of total femur length from the distal growth plate. Measurement units: square millimeters (mm^2). | Baseline to 12-months | 
| 12-month Change in Periosteal Circumference at the Femur 4% Site | Baseline to 12-month change in periosteal circumference at the femur 4% site . Measurement made by pQCT at a distance of 4% of total femur length from the distal growth plate. Measurement units: millimeters (mm). | Baseline to 12-months | 
| 12-month Change in Bone Strength Index at the Femur 4% Site | Baseline to 12-month change in bone strength index (BSI) at the femur 4% site. Bone Strength Index (BSI) is a measurement of the resistance to compression forces at the epiphyses of long bones. Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: mm^4. | Baseline to 12-months | 
| 12-month Change in Total Volumetric Bone Density at the Femur 20% Site | Baseline to 12-month change in total volumetric bone density at the femur 20% site . Measurement made by pQCT at a distance of 20% of total femur length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 12-months | 
| 12-month Change in Volumetric Bone Density of Trabecular Bone at the Femur 20% Site | Baseline to 12-month change in volumetric bone density of trabecular bone at the femur 20% site . Measurement made by pQCT at a distance of 20% of total femur length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 12-months | 
| 12-month Change in Volumetric Bone Density of Cortical Bone at the Femur 20% Site | Baseline to 12-month change in volumetric bone density of cortical bone at the femur 20% site . Measurement made by pQCT at a distance of 20% of total femur length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 12-months | 
| 12-month Change in Thickness of Cortical Bone at the Femur 20% Site | Baseline to 12-month change in thickness of cortical bone at the femur 20% site . Measurement made by pQCT at a distance of 20% of total femur length from the distal growth plate. Measurement units millimeters (mm). | Baseline to 12-months | 
| 12-month Change in Periosteal Circumference at the Femur 20% Site | Baseline to 12-month change in periosteal circumference at the femur 20% site . Measurement made by pQCT at a distance of 20% of total femur length from the distal growth plate. Measurement units: millimeters (mm). | Baseline to 12-months | 
| 12-month Change in Stress-Strain Index at the Femur 20% Site | Baseline to 12-month change in strength-strain index at the femur 20% site. Stress-strain index (also called strength-strain index and stress-strength index in the literature) is a measure of the resistance to torsional and bending forces at diaphyseal sites of long bones. Measurement made by pQCT at a distance of 20% of total femur length from the distal growth plate. Measurement units: mm^3. | Baseline to 12-months | 
| 12-month Change in Total Volumetric Bone Density at the Tibia 4% Site | Baseline to 12-month change in total volumetric bone density at the tibia 4% site . Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 12-months | 
| 12-month Change in Volumetric Bone Density of Trabecular Bone at the Tibia 4% Site | Baseline to 12-month change in volumetric bone density of trabecular bone at the tibia 4% site . Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 12-months | 
| 12-month Change in Volumetric Bone Density of Cortical Bone at the Tibia 4% Site | Baseline to 12-month change in volumetric bone density of cortical bone at the tibia 4% site . Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 12-months | 
| 12-month Change in Trabecular Bone Area at the Tibia 4% Site | Baseline to 12-month change in trabecular bone area at the tibia 4% site . Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: square millimeters (mm^2). | Baseline to 12-months | 
| 12-month Change in Cortical Bone Area at the Tibia 4% Site | Baseline to 12-month change in cortical bone area at the tibia 4% site . Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: square millimeters (mm^2). | Baseline to 12-months | 
| 12-month Change in Periosteal Circumference at the Tibia 4% Site | Baseline to 12-month change in periosteal circumference at the tibia 4% site . Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: millimeters (mm). | Baseline to 12-months | 
| 12-month Change in Bone Strength Index at the Tibia 4% Site | Baseline to 12-month change in bone strength index (BSI) at the tibia 4% site. Bone Strength Index (BSI) is a measurement of the resistance to compression forces at the epiphyses of long bones. Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: mm^4. | Baseline to 12-months | 
| 12-month Change in Total Volumetric Bone Density at the Tibia 50% Site | Baseline to 12-month change in total volumetric bone density at the tibia 50% site . Measurement made by pQCT at a distance of 50% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 12-months | 
| 12-month Change in Volumetric Bone Density of Trabecular Bone at the Tibia 50% Site | Baseline to 12-month change in volumetric bone density of trabecular bone at the tibia 50% site . Measurement made by pQCT at a distance of 50% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 12-months | 
| 12-month Change in Volumetric Bone Density of Cortical Bone at the Tibia 50% Site | Baseline to 12-month change in volumetric bone density of cortical bone at the tibia 50% site . Measurement made by pQCT at a distance of 50% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 12-months | 
| 12-month Change in Periosteal Circumference at the Tibia 50% Site | Baseline to 12-month change in periosteal circumference at the tibia 50% site . Measurement made by pQCT at a distance of 50% of total tibia length from the distal growth plate. Measurement units: millimeters (mm). | Baseline to 12-months | 
| 12-month Change in Cortical Thickness at the Tibia 50% Site | Baseline to 12-month change in cortical thickness at the tibia 50% site . Measurement made by pQCT at a distance of 50% of total tibia length from the distal growth plate. Measurement units: millimeters (mm). | Baseline to 12-months | 
| 12-month Change in Stress-Strain Index at the Tibia 50% Site | Baseline to 12-month change in strength-strain index at the tibia 50% site. Stress-strain index (also called strength-strain index and stress-strength index in the literature) is a measure of the resistance to torsional and bending forces at diaphyseal sites of long bones. Measurement made by pQCT at a distance of 50% of total tibia length from the distal growth plate. Measurement units: mm^3. | Baseline to 12-months | 
| 12-month Change in Total Volumetric Bone Density at the Tibia 66% Site | Baseline to 12-month change in total volumetric bone density at the tibia 66% site . Measurement made by pQCT at a distance of 66% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 12-months | 
| 12-month Change in Volumetric Bone Density of Trabecular Bone at the Tibia 66% Site | Baseline to 12-month change in volumetric bone density of trabecular bone at the tibia 66% site . Measurement made by pQCT at a distance of 66% of total tibia length from the distal growth plate.Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 12-months | 
| 12-month Change in Volumetric Bone Density of Cortical Bone at the Tibia 66% Site | Baseline to 12-month change in volumetric bone density of cortical bone at the tibia 66% site . Measurement made by pQCT at a distance of 66% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 12-months | 
| 12-month Change in Periosteal Circumference at the Tibia 66% Site | Baseline to 12-month change in periosteal circumference at the tibia 66% site . Measurement made by pQCT at a distance of 66% of total tibia length from the distal growth plate. Measurement units: millimeters (mm). | Baseline to 12-months | 
| 12-month Change in Cortical Thickness at the Tibia 66% Site | Baseline to 12-month change in cortical thickness at the tibia 66% site . Measurement made by pQCT at a distance of 66% of total tibia length from the distal growth plate. Measurement units: millimeters (mm). | Baseline to 12-months | 
| 12-month Change in Stress-Strain Index at the Tibia 66% Site | Baseline to 12-month change in strength-strain index at the tibia 66% site. Stress-strain index (also called strength-strain index and stress-strength index in the literature) is a measure of the resistance to torsional and bending forces at diaphyseal sites of long bones. Measurement made by pQCT at a distance of 66% of total tibia length from the distal growth plate. Measurement units: mm^3. | Baseline to 12-months | 
| 24-month in Change in Total Volumetric Bone Density the Femur 4% Site | Baseline to 24-month change in total volumetric bone density at the femur 4% site . Measurement made by pQCT at a distance of 4% of total femur length from the distal growth plate. Measurement units mg/ccm. | Baseline to 24-months | 
| 24-month in Change in Volumetric Bone Density of Trabecular Bone at the Femur 4% Site | Baseline to 24-month change in volumetric bone density of trabecular bone at the femur 4% site . Measurement made by pQCT at a distance of 4% of total femur length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 24-months | 
| 24-month in Change in Volumetric Bone Density of Cortical Bone at the Femur 4% Site | Baseline to 24-month change in volumetric bone density of cortical bone at the femur 4% site . Measurement made by pQCT at a distance of 4% of total femur length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 24-months | 
| 24-month Change in Trabecular Bone Area at the Femur 4% Site | Baseline to 24-month change in trabecular bone area at the femur 4% site . Measurement made by pQCT at a distance of 4% of total femur length from the distal growth plate. Measurement units: square millimeters (mm^2). | Baseline to 24-months | 
| 24-month Change in Cortical Bone Area at the Femur 4% Site | Baseline to 24-month change in cortical bone area at the femur 4% site . Measurement made by pQCT at a distance of 4% of total femur length from the distal growth plate. Measurement units: square millimeters (mm^2). | Baseline to 24-months | 
| 24-month Change in Periosteal Circumference at the Femur 4% Site | Baseline to 24-month change in periosteal circumference at the femur 4% site . Measurement made by pQCT at a distance of 4% of total femur length from the distal growth plate. Measurement units: millimeters (mm). | Baseline to 24-months | 
| 24-month Change in Bone Strength Index at the Femur 4% Site | Baseline to 24-month change in bone strength index (BSI) at the femur 4% site. Bone Strength Index (BSI) is a measurement of the resistance to compression forces at the epiphyses of long bones. Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: mm^4. | Baseline to 24-months | 
| 24-month Change in Total Volumetric Bone Density at the Femur 20% Site | Baseline to 24-month change in total volumetric bone density at the femur 20% site . Measurement made by pQCT at a distance of 20% of total femur length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 24-months | 
| 24-month Change in Volumetric Bone Density of Trabecular Bone at the Femur 20% Site | Baseline to 24-month change in volumetric bone density of trabecular bone at the femur 20% site . Measurement made by pQCT at a distance of 20% of total femur length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 24-months | 
| 24-month Change in Volumetric Bone Density of Cortical Bone at the Femur 20% Site | Baseline to 24-month change in volumetric bone density of cortical bone at the femur 20% site . Measurement made by pQCT at a distance of 20% of total femur length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 24-months | 
| 24-month Change in Thickness of Cortical Bone at the Femur 20% Site | Baseline to 24-month change in thickness of cortical bone at the femur 20% site . Measurement made by pQCT at a distance of 20% of total femur length from the distal growth plate. Measurement units: millimeters (mm). | Baseline to 24-months | 
| 24-month Change in Periosteal Circumference at the Femur 20% Site | Baseline to 24-month change in periosteal circumference at the femur 20% site . Measurement made by pQCT at a distance of 20% of total femur length from the distal growth plate. Measurement units: millimeters (mm). | Baseline to 24-months | 
| 24-month Change in Stress-Strain Index at the Femur 20% Site | Baseline to 24-month change in strength-strain index at the femur 20% site. Stress-strain index (also called strength-strain index and stress-strength index in the literature) is a measure of the resistance to torsional and bending forces at diaphyseal sites of long bones. Measurement made by pQCT at a distance of 20% of total femur length from the distal growth plate. Measurement units: mm^3. | Baseline to 24-months | 
| 24-month Change in Total Volumetric Bone Density at the Tibia 4% Site | Baseline to 24-month change in total volumetric bone density at the tibia 4% site . Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 24-months | 
| 24-month Change in Volumetric Bone Density of Trabecular Bone at the Tibia 4% Site | Baseline to 24-month change in volumetric bone density of trabecular bone at the tibia 4% site . Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 24-months | 
| 24-month Change in Volumetric Bone Density of Cortical Bone at the Tibia 4% Site | Baseline to 24-month change in volumetric bone density of cortical bone at the tibia 4% site . Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 24-months | 
| 24-month Change in Trabecular Bone Area at the Tibia 4% Site | Baseline to 24-month change in trabecular bone area at the tibia 4% site . Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: square millimeters (mm^2). | Baseline to 24-months | 
| 24-month Change in Cortical Bone Area at the Tibia 4% Site | Baseline to 24-month change in cortical bone area at the tibia 4% site . Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: square millimeters (mm^2). | Baseline to 24-months | 
| 24-month Change in Periosteal Circumference at the Tibia 4% Site | Baseline to 24-month change in periosteal circumference at the tibia 4% site . Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: millimeters (mm). | Baseline to 24-months | 
| 24-month Change in Bone Strength Index at the Tibia 4% Site | Baseline to 24-month change in bone strength index (BSI) at the tibia 4% site. Bone Strength Index (BSI) is a measurement of the resistance to compression forces at the epiphyses of long bones. Measurement made by pQCT at a distance of 4% of total tibia length from the distal growth plate. Measurement units: mm^4. | Baseline to 24-months | 
| 24-month Change in Total Volumetric Bone Density at the Tibia 50% Site | Baseline to 24-month change in total volumetric bone density at the tibia 50% site . Measurement made by pQCT at a distance of 50% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 24-months | 
| 24-month Change in Volumetric Bone Density of Trabecular Bone at the Tibia 50% Site | Baseline to 24-month change in volumetric bone density of trabecular bone at the tibia 50% site . Measurement made by pQCT at a distance of 50% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 24-months | 
| 24-month Change in Volumetric Bone Density of Cortical Bone at the Tibia 50% Site | Baseline to 24-month change in volumetric bone density of cortical bone at the tibia 50% site . Measurement made by pQCT at a distance of 50% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 24-months | 
| 24-month Change in Periosteal Circumference at the Tibia 50% Site | Baseline to 24-month measurement of periosteal circumference at the tibia 50% site . Measurement made by pQCT at a distance of 50% of total tibia length from the distal growth plate. Measurement units: millimeters (mm). | Baseline to 24-months | 
| 24-month Change in Cortical Thickness at the Tibia 50% Site | Baseline to 24-month change in cortical thickness at the tibia 50% site . Measurement made by pQCT at a distance of 50% of total tibia length from the distal growth plate. Measurement units: millimeters (mm). | Baseline to 24-months | 
| 24-month Change in Stress-Strain Index at the Tibia 50% Site | Baseline to 24-month change in strength-strain index at the tibia 50% site. Stress-strain index (also called strength-strain index and stress-strength index in the literature) is a measure of the resistance to torsional and bending forces at diaphyseal sites of long bones. Measurement made by pQCT at a distance of 50% of total tibia length from the distal growth plate. Measurement units: mm^3. | Baseline to 24-months | 
| 24-month Change in Total Volumetric Bone Density at the Tibia 66% Site | Baseline to 24-month change in total volumetric bone density at the tibia 66% site . Measurement made by pQCT at a distance of 66% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 24-months | 
| 24-month Change in Volumetric Bone Density of Trabecular Bone at the Tibia 66% Site | Baseline to 24-month change in volumetric bone density of trabecular bone at the tibia 66% site . Measurement made by pQCT at a distance of 66% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 24-months | 
| 24-month Change in Volumetric Bone Density of Cortical Bone at the Tibia 66% Site | Baseline to 24-month change in volumetric bone density of cortical bone at the tibia 66% site . Measurement made by pQCT at a distance of 66% of total tibia length from the distal growth plate. Measurement units: milligrams per cubic centimeter (mg/ccm). | Baseline to 24-months | 
| 24-month Change in Periosteal Circumference at the Tibia 66% Site | Baseline to 24-month change in periosteal circumference at the tibia 66% site . Measurement made by pQCT at a distance of 66% of total tibia length from the distal growth plate. Measurement units: millimeters (mm). | Baseline to 24-months | 
| 24-month Change in Cortical Thickness at the Tibia 66% Site | Baseline to 24-month change in cortical thickness at the tibia 66% site . Measurement made by pQCT at a distance of 66% of total tibia length from the distal growth plate. Measurement units: millimeters (mm). | Baseline to 24-months | 
| 24-month Change in Stress-Strain Index at the Tibia 66% Site | Baseline to 24-month change in strength-strain index at the tibia 66% site. Stress-strain index (also called strength-strain index and stress-strength index in the literature) is a measure of the resistance to torsional and bending forces at diaphyseal sites of long bones. Measurement made by pQCT at a distance of 66% of total tibia length from the distal growth plate. Measurement units: mm^3. | Baseline to 24-months |