Effects of Low-level Mechanical Vibration on Bone Density in Ambulant Children Affected by Duchenne Muscular Dystrophy

Study Overview
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Brief Summary
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Duchenne muscular dystrophy (DMD) is a X-linked recessive disorder due to a mutation of the dystrophin gene (Xp21). Dystrophin is a sarcolemmal protein of skeletal and cardiac muscle, and its absence causes progressive muscle degeneration and substitution with fat and connective tissue. The progressive muscle degeneration leads to loss of autonomous walking before the age of 15 years and death for cardiac and/or respiratory failure. There are no specific treatment for DMD, and the standard of care is now based on long-term corticosteroid (CS) use. The studies on bone mass in DMD are very few, but they agree in reporting the presence of a reduced bone mass and an increased rate of fractures probably due to long-term steroid therapy and disuse-osteopenia. The aim of this study, involving 20 ambulant DMD boys (age 7-10 years) has been the evaluation of the effects of low-level mechanical vibrations on bone in a group of ambulant DMD children for 1 year, with RDA-adjusted dietary calcium intake and 25OH vitamin D supplementation.

Detailed Description
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All children were instructed to have a daily intake of calcium equal to the 100% of the RDA and were supplemented with calcifediol (0.7 mcg/kg/die). The 20 boys were randomly assigned to two groups: group 1 (mechanical intervention group) = a mechanical device (a small platform designed to induce vertical, sinusoidal acceleration) was installed in the home of each boy of group 1. group 2 (placebo control group) = a placebo device was installed in the home of each boy of group 2 All boys were instructed to stand on the platform for 10 minutes each day for 12 months. Compliance was followed and stimulated through weekly telephone contacts with parents and children.

Official Title
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Low-level Mechanical Vibration, Bone Density, Bone Resorption and Muscular Strength in Ambulant Children Affected by Duchenne Muscular Dystrophy

Conditions
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Osteoporosis, Duchenne Muscular Dystrophy

Intervention / Treatment
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* Device: Low-level mechanical vibrations WITH vertical sinusoidal acceleration
* Device: Low-level mechanical vibrations WITHOUT vertical sinusoidal acceleration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of DMD Ability to stand up and walk (some balance assistance allowed, but full weight-bearing necessary) All the children must already be on glucocorticoid therapy for at least 6 months before the start of the study. Exclusion Criteria: Presence of other diseases interfering with bone density and bone turnover The inability to regularly use the vibratory platform.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 10 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: mechanical intervention group<br>20 subjects participated to the study (1 year double-blind, randomized, placebo controlled, parallel group study) and 10 subjects were randomized to this arm. Intervention: to stand on the active platform (inducing vertical, sinusoidal acceleration) for 10 minutes each day for 12 months. | Device: Low-level mechanical vibrations WITH vertical sinusoidal acceleration<br>* Small platform designed to induce vertical, sinusoidal acceleration.<br>|
| Placebo Comparator: mechanical placebo group<br>20 subjects participated to the study (1 year double-blind, randomized, placebo controlled, parallel group study) and 10 subjects were randomized to this arm. Intervention: to stand on the placebo platform (not inducing vertical, sinusoidal acceleration) for 10 minutes each day for 12 months. | Device: Low-level mechanical vibrations WITHOUT vertical sinusoidal acceleration<br>* Small platform designed to NOT induce vertical, sinusoidal acceleration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in bone mineral density at lumbar spine. | Bone mineral density evaluated by DXA. Bone mineral apparent density calculated to correct for bone size (growing subjects). Z-score calculated. Measurements: baseline and 12 months. | baseline and 12th month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calcium | changes in serum calcium (mg/dL) | baseline and 12th month | 
| Phosphate | changes in serum phosphate (mg/dL) | baseline and 12th month | 
| Magnesium | changes in serum magnesium (mg/dL) | baseline and 12th month | 
| Creatinine | changes in serum creatinine (mg/dL) | baseline and 12th month | 
| Bone Alkaline Phosphatase | changes in serum bone alkaline phosphatase (µg/L) | baseline and 12th month | 
| Osteocalcin | changes in serum osteocalcin (µg/L) | baseline and 12th month | 
| Parathyroid Hormone | changes in serum parathyroid hormone (ng/L) | baseline and 12th month | 
| 25-OH vitamin D | changes in serum 25-OH vitamin D (µg/L) | baseline and 12th month | 
| 1,25(OH)2 vitamin D | changes in serum 1,25(OH)2 vitamin D (ng/L) | baseline and 12th month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Duchenne Muscular Dystrophy, children, low bone mass, osteoporosis, low-level mechanical vibration, bone turnover markers