title: Bone marrow fat accumulation after 60 days of bed rest persisted 1 year after activities were resumed along with hemopoietic stimulation: the Women International Space Simulation for Exploration study.
abstract: Immobility in bed and decreased mobility cause adaptations to most human body systems. The effect of immobility on fat accumulation in hemopoietic bone marrow has never been measured prospectively. The reversibility of marrow fat accumulation and the effects on hemopoiesis are not known. In the present study, 24 healthy women (age: 25-40 yr) underwent -6 degrees head-down bed rest for 60 days. We used MRI to noninvasively measure the lumbar vertebral fat fraction at various time points. We also measured hemoglobin, erythropoietin, reticulocytes, leukocytes, platelet count, peripheral fat mass, leptin, cortisol, and C-reactive protein during bed rest and for 1 yr after bed rest ended. Compared with baseline, the mean (+/-SE) fat fraction was increased after 60 days of bed rest (+2.5+/-1.1%, P<0.05); the increase persisted 1 yr after the resumption of regular activities (+2.3+/-0.8%, P<0.05). Mean hemoglobin levels were significantly decreased 6 days after bed rest ended (-1.36+/-0.20 g/dl, P<0.05) but had recovered at 1 yr, with significantly lower mean circulating erythropoietin levels (-3.8+/-1.2 mU/ml, P<0.05). Mean numbers of neutrophils and lymphocytes remained significantly elevated at 1 yr (+617+/-218 neutrophils/microl and +498+/-112 lymphocytes/microl, both P<0.05). These results constitute direct evidence that bed rest irreversibly accelerated fat accumulation in hemopoietic bone marrow. The 2.5% increase in fat fraction after 60 days of bed rest was 25-fold larger than expected from historical ambulatory controls. Sixty days of bed rest accelerated by 4 yr the normal bone marrow involution. Bed rest and marrow adiposity were associated with hemopoietic stimulation. One year after subjects returned to normal activities, hemoglobin levels were maintained, with 43% lower circulating erythropoietin levels, and leukocytes remained significantly elevated across lineages. Lack of mobility alters hemopoiesis, possibly through marrow fat accumulation, with potentially wide-ranging clinical consequences.
authors.affiliation: Bone and Joint Laboratory, University of Ottawa, The Ottawa Hospital Rehabilitation Centre, 505 Smyth Rd., Ottawa, ON, Canada K1H 8M2. gtrudel@ottawahospital.on.ca
authors.forename: Guy
authors.initials: G
authors.lastname: Trudel
authors.forename: Michael
authors.initials: M
authors.lastname: Payne
authors.forename: Burkhard
authors.initials: B
authors.lastname: Mädler
authors.forename: Nanthan
authors.initials: N
authors.lastname: Ramachandran
authors.forename: Martin
authors.initials: M
authors.lastname: Lecompte
authors.forename: Charles
authors.initials: C
authors.lastname: Wade
authors.forename: Gianni
authors.initials: G
authors.lastname: Biolo
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanc
authors.forename: Richard
authors.initials: R
authors.lastname: Hughson
authors.forename: Lisa
authors.initials: L
authors.lastname: Bear
authors.forename: Hans K
authors.initials: HK
authors.lastname: Uhthoff
mesh_terms: D050154:Adiposity; D000328:Adult; D001510:Bed Rest; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D001856:Bone Marrow Examination; D004921:Erythropoietin / Q000097:blood; D005260:Female; D018475:Head-Down Tilt; D006410:Hematopoiesis; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007391:International Cooperation; D007958:Leukocyte Count; D008159:Lumbar Vertebrae; D008214:Lymphocytes / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009504:Neutrophils / Q000473:pathology; D011446:Prospective Studies; D012156:Reticulocytes / Q000473:pathology; D013026:Space Flight; D013997:Time Factors; D018474:Weightlessness Simulation; D016387:Women's Health
chemical_list: D006454:Hemoglobins; D004921:Erythropoietin