title: Reduced bone formation markers, and altered trabecular and cortical bone mineral densities of non-paretic femurs observed in rats with ischemic stroke: A randomized controlled pilot study.
abstract: BACKGROUND
  Immobility and neural damage likely contribute to accelerated bone loss after stroke, and subsequent heightened fracture risk in humans.
  
  
  OBJECTIVE
  To investigate the skeletal effect of middle cerebral artery occlusion (MCAo) stroke in rats and examine its utility as a model of human post-stroke bone loss.
  
  
  METHODS
  Twenty 15-week old spontaneously hypertensive male rats were randomized to MCAo or sham surgery controls. Primary outcome: group differences in trabecular bone volume fraction (BV/TV) measured by Micro-CT (10.5 micron istropic voxel size) at the ultra-distal femur of stroke affected left legs at day 28. Neurological impairments (stroke behavior and foot-faults) and physical activity (cage monitoring) were assessed at baseline, and days 1 and 27. Serum bone turnover markers (formation: N-terminal propeptide of type 1 procollagen, PINP; resorption: C-terminal telopeptide of type 1 collagen, CTX) were assessed at baseline, and days 7 and 27.
  
  
  RESULTS
  No effect of stroke was observed on BV/TV or physical activity, but PINP decreased by -24.5% (IQR -34.1, -10.5, p = 0.046) at day 27. In controls, cortical bone volume (5.2%, IQR 3.2, 6.9) and total volume (6.4%, IQR 1.2, 7.6) were higher in right legs compared to left legs, but these side-to-side differences were not evident in stroke animals.
  
  
  CONCLUSIONS
  MCAo may negatively affect bone formation. Further investigation of limb use and physical activity patterns after MCAo is required to determine the utility of this current model as a representation of human post-stroke bone loss.
authors.affiliation: School of Allied Health, La Trobe University, Bundoora, Australia.|Stroke Division, The Florey Institute of Neuroscience and Mental Health, Heidelberg, Australia.|NHMRC Centre for Research Excellence in Stroke Rehabilitation and Recovery, Melbourne, Australia.
authors.forename: Karen N
authors.identifier: http://orcid.org/0000-0001-5364-2718
authors.initials: KN
authors.lastname: Borschmann
authors.affiliation: Stroke Division, The Florey Institute of Neuroscience and Mental Health, Heidelberg, Australia.
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Rewell
authors.affiliation: Department of Endocrinology, Austin Health, University of Melbourne, Heidelberg, Australia.|Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Australia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Iuliano
authors.affiliation: Department of Endocrinology, Austin Health, University of Melbourne, Heidelberg, Australia.|Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Australia.
authors.forename: Ali
authors.initials: A
authors.lastname: Ghasem-Zadeh
authors.affiliation: Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Australia.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Davey
authors.affiliation: Stroke Division, The Florey Institute of Neuroscience and Mental Health, Heidelberg, Australia.
authors.forename: Heidi
authors.initials: H
authors.lastname: Ho
authors.affiliation: Stroke Division, The Florey Institute of Neuroscience and Mental Health, Heidelberg, Australia.
authors.forename: Peta N
authors.initials: PN
authors.lastname: Skeers
authors.affiliation: School of Allied Health, La Trobe University, Bundoora, Australia.|Stroke Division, The Florey Institute of Neuroscience and Mental Health, Heidelberg, Australia.|NHMRC Centre for Research Excellence in Stroke Rehabilitation and Recovery, Melbourne, Australia.
authors.forename: Julie
authors.initials: J
authors.lastname: Bernhardt
authors.affiliation: Stroke Division, The Florey Institute of Neuroscience and Mental Health, Heidelberg, Australia.|University of Tasmania, School of Medicine, Faculty of Health, Hobart, Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Howells
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D001835:Body Weight; D015519:Bone Density; D016723:Bone Remodeling; D016022:Case-Control Studies; D024042:Collagen Type I / Q000097:blood; D000071538:Cortical Bone / Q000000981:diagnostic imaging / Q000378:metabolism*; D004195:Disease Models, Animal; D005269:Femur / Q000000981:diagnostic imaging / Q000378:metabolism*; D009043:Motor Activity; D010446:Peptide Fragments / Q000097:blood; D010865:Pilot Projects; D011347:Procollagen / Q000097:blood; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; C000615613:CTX-I peptide, rat; D024042:Collagen Type I; D010446:Peptide Fragments; D011347:Procollagen; C047202:procollagen Type I N-terminal peptide