Planetary Habitat Simulation: Bone Metabolism Studies
Condition: Hypoxia; Bone Resorption
MeSH terms: Bone Resorption; Hypoxia
Study type: Interventional

Summary: 
      Bone losses are well known to occur in response to unloading (in microgravity or during
      immobilisation) and in patients with chronic obstructive airway disease (COPD). However, it
      is unknown whether there is an interactive effect between hypoxia and musculoskeletal
      unloading upon bone and mineral metabolism. Fourteen non-obese men, who are otherwise
      healthy, will undergo 3x 21-day interventions; normobaric normoxic bed rest (NBR; FiO2=21%),
      normobaric hypoxic ambulatory confinement (HAMB; FiO2=14%; ~4000 m simulated altitude), and
      normobaric hypoxic bed rest (HBR; FiO2=14%). The effects of hypoxia and bedrest on bone
      metabolism and phosphor-calcic homeostasis will be assessed (before and during each
      intervention, and 14 days after each intervention period) using venous blood sampling, 24hr
      urine collections, and peripheral quantitative computerized tomography (pQCT).
    

Detailed description: 
      The risk of bone loss in response to immobilization and space flight is widely recognized,
      with such bone losses occurring predominantly in the legs. Loading forces in the lower
      extremities are typically low in space and during bed rest, but musculoskeletal loading
      countermeasures can prevent or reduce bone losses induced in these conditions. Although the
      primary origin may be of a mechanical nature, bone losses in astronauts and immobilized
      patients are likely to be modulated by the endocrine and the internal environment.

      Bone loss and osteoporosis is also prevalent in those with chronic obstructive pulmonary
      disease (COPD). The most discussed etiological factors for this condition include lack of
      physical activity, vitamin-D deficiency, hypogonadism, use of corticosteroids and smoking.
      However, COPD is associated with tissue hypoxemia and it is unclear whether hypoxia per se
      will affect bone turnover or metabolism.

      The protocol of the current study standardises potential confounding factors, such as
      physical activity, ambient temperature, hypoxic stimulus and nutritional composition of the
      diet across all 3 interventions, and aims to extend our knowledge of the effects of hypoxia
      and bedrest on bone metabolism and phospho-calcic homeostasis.

      Fourteen non-obese men, who are otherwise healthy, will be recruited following medical and
      psychological screening. They will be invited to attend the Olympic Sport Centre, Planica,
      Slovenia on 3 occasions, with each visit being 31 days in duration and separated by 5 months.
      Each 31-day visit ('campaign') includes a baseline recording period (5 days), 21 days of
      intervention, and a recovery period (5 days), with a follow-up visit being carried out 14
      days after each intervention. The 3 interventions will be allocated in a randomized, cross
      over design: i) Normobaric normoxic bed rest (NBR; FiO2=21%), ii) Normobaric hypoxic
      ambulatory confinement (HAMB; FiO2=14%; ~4000 m simulated altitude), and iii) Normobaric
      hypoxic bed rest (HBR; FiO2=14%). A standardized, repeating, 14-day dietary menu, comprised
      of foods commonly consumed in the Slovenian diet, will be applied during all campaigns.
      Targeted energy intakes will be calculated individually using a modified Benedict-Harris
      formula, with physical activity factor multipliers of 1.2 for the HBR and NBR campaigns and
      1.4 for the HAMB campaign, used to promote energy balance. Body mass will be monitored daily
      during the campaigns using a gurney incorporating load cells, and whole body composition will
      be determined before and immediately after each intervention using fan beam dual-emission
      X-ray absorptiometry. Macronutrient composition of the diet will be approximately 17%
      protein, 53% carbohydrate and 30% fat, with >1.1g of protein per kg body weight provided per
      day, and daily salt (sodium chloride) intake being <10g. Food will be provided in weighed
      portions and subjects will be encouraged to eat all food supplied. However, any food not
      eaten will be weighed and actual amount consumed recorded in a diet analysis programme.

      Participants will have bone mineral content assessed at 5 time points (before, 3 during and
      one after each intervention) using pQCT scans of the calf and thigh. Horizontal scans will be
      taken at 4%, 14%, 38%, and 66% of the tibia (assessed from its distal end), and at 4% and 33%
      of the femur. Twenty-four hour urine collections will be obtained before (2 time points),
      during (11 time points) and after (3 time points) each intervention, and will be assessed for
      urinary calcium and phosphate content, and for a marker of bone reabsorption (N-terminal
      telopeptide). In addition, early morning, fasting venous blood samples will also be taken
      before (2 time points), and during (5 time points) each intervention. These will be analysed
      for calcium, phosphate, bone specific alkaline phosphatase, parathyroid hormone,
      25-Hydroxyvitamin D, Procollagen-I-N-terminal propeptide and regulators of bone metabolism,
      (Dickkopf-related protein 1 and Sclerostin).
    

Intervention name(s): Hypoxia; Ambulatory; Normoxia; Bed Rest; Standardised nutritional intake
Intervention type(s): Other; Other; Other; Other; Other
Intervention description(s): 21 days confinement in normobaric hypoxic (FiO2 = 14%); Participants hava a standardized activity level throughout the intervention; 21 days confinement in normobaric normoxic (FiO2 = 21%) environment; Participants remain on supine bed rest throughout the intervention; Macronutrient, salt and dietary energy intake will be standardized per kg body weight for each participant
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: bed rest; bone metabolism