Mechanical Bone Stimulation and Adenosine 5'-Triphosphate (ATP) Release in Humans
Rationale: Mechanical loading is well-known to have a strong anabolic effect on bone. It has therefore been proposed that a mechanical intervention could be an effective non-pharmacological approach to treat bone loss associated with conditions such as osteopenia and osteoporosis. Data from in vitro experiments indicate that the purine nucleotide adenosine 5'-triphosphate (ATP) is released by bone cells and mediates cellular crosstalk via P2 purinergic receptors in response to mechanical stimulation. ATP release by bone cells may thus be part of a general mechanism by which mechanical loading ultimately results in increased bone formation, but this remains to be investigated in humans in vivo. The investigators hypothesize that a mechanical intervention in humans leads to a rise in systemic ATP concentrations due to ATP release from bone.
Objective: To investigate in vivo whether a measurable increase in systemic ATP levels occurs in response to mechanical stimulation of bone in humans.
Study design: Intervention study with a non-randomized, non-blinded design. All subjects will participate in a single experiment, lasting approximately 3 hours, during which the subjects will receive a mechanical intervention at a fixed dose.
Study population: Maximally 10 healthy human volunteers (18-35 y). Intervention: Subjects will receive a gentle and safe mechanical intervention, which will be administered by means of a Juvent 1000 Vibration Platform delivering low-magnitude mechanical stimuli (i.e. vibrations) to the forearm. The mechanical stimulation will be administered at a frequency of 90 Hz and amplitude of 10 µm in an intermittent fashion, i.e. three 10-minute periods of stimulation with 10-minute rest periods in between.
Main outcome parameters: As the primary outcome parameter, a change in extracellular ATP concentrations as a result of the mechanical intervention will be assessed systemically.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||Pilot Study on the Effect of Mechanical Stimulation of Bone on ATP Release in Humans in Vivo|
- Change in systemic ATP levels in response to mechanical stimulation [ Time Frame: Pre-post treatment comparison ] [ Designated as safety issue: No ]As the primary outcome parameter, ATP release from bone after a mechanical intervention will be investigated in humans in vivo by assessing a change in systemic concentrations of ATP and its metabolites in response to mechanical stimulation as an objective outcome measure. A change in levels of ATP (or its metabolites) is defined as the average of three concentrations after the intervention minus the average of three concentrations before the intervention (i.e. baseline).
|Study Start Date:||October 2010|
|Study Completion Date:||December 2010|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
Experimental: Intervention group
As a mechanical intervention, we will use a vibration platform to administer mechanical stimulation to the forearm of subjects (see Figure 1). All subjects will participate in a single experiment during which they will receive the mechanical intervention a fixed dose of; the duration of an experiment is approximately three hours.
Device: Juvent 1000 Vibration Platform
As a mechanical intervention, mechanical stimulation in the form of vibration will be administered to the forearm using a Juvent 1000 Vibration Platform (Juvent Medical, Inc., Lakeland, FL, USA), which is a non-medicinal product. The device produces gentle, low-magnitude mechanical signals in the form of low-amplitude vertical displacements at a high frequency.
The intervention in the present study will be given at a fixed dosage that is defined by the intensity of vibration: frequency: 90 Hz, amplitude: 10 µm (~3.0 g). The mechanical stimulation will be administered in an intermittent fashion, as it has been shown that inserting short rest periods between loading cycles enhances the efficacy of mechanical loading . Thus, the mechanical stimulation will be administered for three times 10 minutes (i.e. the vibration platform turned on), with 10-minute rest periods in between (i.e. the vibration platform turned off); the intervention will have a total duration of 50 minutes.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01130428
|Maastricht University Medical Center|
|Maastricht, Netherlands, 6200 MD|
|Study Chair:||PC Dagnelie, PhD||Maastricht University Medical Center, Department of Epidemiology|
|Principal Investigator:||MJL Bours, PhD||Maastricht University Medical Center, Department of Epidemiology|