title: On the combined effects of normobaric hypoxia and bed rest upon bone and mineral metabolism: Results from the PlanHab study.
abstract: Bone losses are common as a consequence of unloading and also in patients with chronic obstructive pulmonary disease (COPD). Although hypoxia has been implicated as an important factor to drive bone loss, its interaction with unloading remains unresolved. The objective therefore was to assess whether human bone loss caused by unloading could be aggravated by chronic hypoxia. In a cross-over designed study, 14 healthy young men underwent 21-day interventions of bed rest in normoxia (NBR), bed rest in hypoxia (HBR), and hypoxic ambulatory confinement (HAmb). Hypoxic conditions were equivalent to 4000m altitude. Bone metabolism (NTX, P1NP, sclerostin, DKK1) and phospho-calcic homeostasis (calcium and phosphate serum levels and urinary excretion, PTH) were assessed from regular blood samples and 24-hour urine collections, and tibia and femur bone mineral content was assessed by peripheral quantitative computed tomography (pQCT). Urinary NTX excretion increased (P<0.001) to a similar extent in NBR and HBR (P=0.69) and P1NP serum levels decreased (P=0.0035) with likewise no difference between NBR and HBR (P=0.88). Serum total calcium was increased during bed rest by 0.059 (day D05, SE 0.05mM) to 0.091mM (day D21, P<0.001), with no additional effect by hypoxia during bed rest (P=0.199). HAmb led, at least temporally, to increased total serum calcium, to reduced serum phosphate, and to reduced phosphate and calcium excretion. In conclusion, hypoxia did not aggravate bed rest-induced bone resorption, but led to changes in phospho-calcic homeostasis likely caused by hyperventilation. Whether hyperventilation could have mitigated the effects of hypoxia in this study remains to be established.
authors.affiliation: Institute of Aerospace Medicine, German Aerospace Center (DLR), 51147 Cologne, Germany; Department of Pediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany. Electronic address: joern.rittweger@dlr.de.
authors.forename: Jörn
authors.initials: J
authors.lastname: Rittweger
authors.affiliation: Department of Automation, Biocybernetics and Robotics, Jozef Stefan Institute, Ljubljana, Slovenia.
authors.forename: Tadej
authors.initials: T
authors.lastname: Debevec
authors.affiliation: Institute of Aerospace Medicine, German Aerospace Center (DLR), 51147 Cologne, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Frings-Meuthen
authors.affiliation: Institute of Aerospace Medicine, German Aerospace Center (DLR), 51147 Cologne, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lau
authors.affiliation: Institute of Aerospace Medicine, German Aerospace Center (DLR), 51147 Cologne, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Mittag
authors.affiliation: Institute of Aerospace Medicine, German Aerospace Center (DLR), 51147 Cologne, Germany.
authors.forename: Bergita
authors.initials: B
authors.lastname: Ganse
authors.affiliation: Medizinische Klinik I, University of Frankfurt, Frankfurt, Germany.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Ferstl
authors.affiliation: MRC/Arthritis UK Centre for Musculoskeletal Aging Research, University of Nottingham Medical School, School of Life Sciences, Queen's Medical Centre, Nottingham, United Kingdom.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Simpson
authors.affiliation: MRC/Arthritis UK Centre for Musculoskeletal Aging Research, University of Nottingham Medical School, School of Life Sciences, Queen's Medical Centre, Nottingham, United Kingdom.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Macdonald
authors.affiliation: Department of Environmental Physiology, Swedish Aerospace Physiology Centre, Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Eiken
authors.affiliation: Department of Automation, Biocybernetics and Robotics, Jozef Stefan Institute, Ljubljana, Slovenia; Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Igor B
authors.initials: IB
authors.lastname: Mekjavic
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D001510:Bed Rest; D015519:Bone Density; D019485:Bone Morphogenetic Proteins / Q000097:blood; D001842:Bone and Bones / Q000378:metabolism*; D002118:Calcium / Q000097:blood / Q000652:urine; D002245:Carbon Dioxide / Q000378:metabolism; D005819:Genetic Markers; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008297:Male; D008903:Minerals / Q000378:metabolism*; D010012:Osteogenesis; D010281:Parathyroid Hormone / Q000097:blood; D010313:Partial Pressure; D010446:Peptide Fragments / Q000097:blood; D010710:Phosphates / Q000097:blood / Q000652:urine; D011347:Procollagen / Q000097:blood
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D008903:Minerals; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010710:Phosphates; D011347:Procollagen; C422903:SOST protein, human; C047202:procollagen Type I N-terminal peptide; D002245:Carbon Dioxide; D000469:Alkaline Phosphatase; D002118:Calcium
keywords: DKK1; Human physiology; Immobilization; Respiration; Sclerostin