Mechanical Bone Stimulation and Adenosine 5'-Triphosphate (ATP) Release in Humans
Condition: Osteoporosis
MeSH terms: Osteoporosis
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    


Intervention name(s): Juvent 1000 Vibration Platform
Intervention type(s): Device
Intervention description(s): 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 [38]. 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.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Mechanical stimulation; Vibration platform; Bone metabolism; ATP release