title: Patient-specific bone mineral density distribution in the tibia of individuals with chronic spinal cord injury, derived from multi-slice peripheral Quantitative Computed Tomography (pQCT) - A cross-sectional study.
abstract: The high risk of fracture associated with chronic spinal cord injury (SCI) is attributed to extensive disuse-related bone loss in previously weight-bearing long bones. Changes in bone mineral density (BMD) after SCI have been documented extensively for the epiphyses of the tibia and femur, fracture-prone sites in this patient group. Less attention has been given to patterns of cortical bone loss in the diaphyses, but variability in BMD distributions throughout the long bones may contribute to some patients' increased susceptibility to shaft fractures in chronic SCI.
  
  
  
  A cross-sectional study was carried out to determine whether BMD distributions along the tibia differ between individuals with chronic SCI and healthy able-bodied (AB) controls, in both the trabecular and cortical bone compartments. The effects of time post-injury and gender on BMD distribution were also explored.
  
  
  
  Individuals with chronic (≥6months post-injury) motor-complete SCI were recruited from the Queen Elizabeth National Spinal Injuries Unit (Glasgow, UK). AB control subjects were recruited to achieve similar age and gender profiles for the SCI and control groups. Multi-slice pQCT (XCT3000, Stratec) was performed along the length of the tibia (2mm thickness, 0.5mm voxel size), at 1% intervals in the epiphyses and 5% intervals in the diaphysis (34 slices in total). These were used to reconstruct full 3-D subject-specific models (Mimics, Materialise) of BMD distribution, by interpolating between slices. Subjects with chronic SCI were subdivided into 'early' (<4years post-injury) and 'established' SCI (≥4years post-injury). Subject-specific BMD distribution was described according to new parameters determined from the 3-D patient-specific models, quantifying descriptors of the trabecular and cortical BMD regions separately (volume, peak BMD, half-peak width, area under the curve). These were compared between sub-groups (using independent-samples t-tests or Mann-Whitney tests, significance level of 5%).
  
  
  
  11 men (age range 17-59years old; mean 35.7±10.6) and 3 post-menopausal women (age range 56-58years old; mean 56.7±1.2years) with motor-complete SCI (ranging from 6months to 27years post-injury) were recruited; 6 men (age range 20-56years old; 33.0±12.7years) and 1 post-menopausal woman (56years) formed the AB control group. Overall, SCI resulted in lower BMD at both trabecular and cortical regions of the tibia. In men, longer time since injury resulted in greater BMD differences when compared to AB, throughout the tibia. For the post-menopausal women, differences in BMD between SCI and AB were greater in cortical bone than in trabecular bone. From the models, individual BMD distribution curves showed healthy double-peaks in AB subjects: one trabecular peak (around 200-300mg/cm3) and the other cortical (around 1000-1100mg/cm3). In most subjects with established SCI, trabecular peaks were exaggerated whilst the cortical peaks were barely discernible, with crucially some individuals already exhibiting a diminishing cortical BMD peak even <4years post-injury.
  
  
  
  These findings may have implications for determining the fracture susceptibility of the long bones in individual patients with SCI. Epiphyseal fractures associated with low trabecular BMD are well characterised, but our data show that some individuals with SCI may also be at higher risk of shaft fractures. The proposed BMD distribution description parameters, determined from patient-specific models, could be used to identify patients with a weakened diaphysis who may be susceptible to fractures of the tibial shaft, but this requires validation.
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, University of Strathclyde, Glasgow G4 0NW, UK; Scottish Centre for Innovation in Spinal Cord Injury, Queen Elizabeth National Spinal Injuries Unit, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK. Electronic address: sylvie.coupaud@strath.ac.uk.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Coupaud
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, University of Strathclyde, Glasgow G4 0NW, UK; Institute for Biomedical and Neural Engineering, School of Science & Engineering, University of Reykjavik, Menntavegi 1, 101 Reykjavik, Iceland.
authors.forename: Magnus K
authors.initials: MK
authors.lastname: Gislason
authors.affiliation: Scottish Centre for Innovation in Spinal Cord Injury, Queen Elizabeth National Spinal Injuries Unit, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK.
authors.forename: Mariel
authors.initials: M
authors.lastname: Purcell
authors.affiliation: Department of Engineering, Niigata Institute of Technology, 1719 Fujihashi, Kashiwazaki City, Niigata 945-1195, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sasagawa
authors.affiliation: Biomedical Engineering Division, School of Engineering, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: K Elizabeth
authors.initials: KE
authors.lastname: Tanner
mesh_terms: D000293:Adolescent; D000328:Adult; D015519:Bone Density; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D061330:Multidetector Computed Tomography / Q000379:methods*; D017698:Postmenopause; D013119:Spinal Cord Injuries / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D013977:Tibia / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D055815:Young Adult