title: Focal osteoporosis defects play a key role in hip fracture.
abstract: Hip fractures are mainly caused by accidental falls and trips, which magnify forces in well-defined areas of the proximal femur. Unfortunately, the same areas are at risk of rapid bone loss with ageing, since they are relatively stress-shielded during walking and sitting. Focal osteoporosis in those areas may contribute to fracture, and targeted 3D measurements might enhance hip fracture prediction. In the FEMCO case-control clinical study, Cortical Bone Mapping (CBM) was applied to clinical computed tomography (CT) scans to define 3D cortical and trabecular bone defects in patients with acute hip fracture compared to controls. Direct measurements of trabecular bone volume were then made in biopsies of target regions removed at operation.
  
  
  
  The sample consisted of CT scans from 313 female and 40 male volunteers (158 with proximal femoral fracture, 145 age-matched controls and 50 fallers without hip fracture). Detailed Cortical Bone Maps (c.5580 measurement points on the unfractured hip) were created before registering each hip to an average femur shape to facilitate statistical parametric mapping (SPM). Areas where cortical and trabecular bone differed from controls were visualised in 3D for location, magnitude and statistical significance. Measures from the novel regions created by the SPM process were then tested for their ability to classify fracture versus control by comparison with traditional CT measures of areal Bone Mineral Density (aBMD). In women we used the surgical classification of fracture location ('femoral neck' or 'trochanteric') to discover whether focal osteoporosis was specific to fracture type. To explore whether the focal areas were osteoporotic by histological criteria, we used micro CT to measure trabecular bone parameters in targeted biopsies taken from the femoral heads of 14 cases.
  
  
  
  Hip fracture patients had distinct patterns of focal osteoporosis that determined fracture type, and CBM measures classified fracture type better than aBMD parameters. CBM measures however improved only minimally on aBMD for predicting any hip fracture and depended on the inclusion of trabecular bone measures alongside cortical regions. Focal osteoporosis was confirmed on biopsy as reduced sub-cortical trabecular bone volume.
  
  
  
  Using 3D imaging methods and targeted bone biopsy, we discovered focal osteoporosis affecting trabecular and cortical bone of the proximal femur, among men and women with hip fracture.
authors: Department of Medicine, University of Cambridge and Addenbrooke's Hospital, Hills Road, Cambridge, UK. Electronic address: Kenneth.poole@nhs.net.
authors: Kenneth E S
authors: KES
authors: Poole
authors: Department of Medicine, University of Cambridge and Addenbrooke's Hospital, Hills Road, Cambridge, UK.
authors: Linda
authors: L
authors: Skingle
authors: Department of Engineering, University of Cambridge, Cambridge, UK.
authors: Andrew H
authors: AH
authors: Gee
authors: Department of Medicine, University of Cambridge and Addenbrooke's Hospital, Hills Road, Cambridge, UK.
authors: Thomas D
authors: TD
authors: Turmezei
authors: Department of Medicine, University of Cambridge and Addenbrooke's Hospital, Hills Road, Cambridge, UK.
authors: Fjola
authors: F
authors: Johannesdottir
authors: Department of Medicine, University of Cambridge and Addenbrooke's Hospital, Hills Road, Cambridge, UK.
authors: Karen
authors: K
authors: Blesic
authors: Department of Medicine, University of Cambridge and Addenbrooke's Hospital, Hills Road, Cambridge, UK.
authors: Collette
authors: C
authors: Rose
authors: Medicine for the Elderly, Addenbrooke's Hospital, Hills Road, Cambridge, UK.
authors: Madhavi
authors: M
authors: Vindlacheruvu
authors: Department of Orthopaedics, Norfolk & Norwich University Hospital, Norwich, UK.
authors: Simon
authors: S
authors: Donell
authors: Department of Orthopaedics, Faculty of Medicine, Charles University and Bulovka Hospital, Prague, Czech Republic.
authors: Jan
authors: J
authors: Vaculik
authors: Department of Orthopaedics, Faculty of Medicine, Charles University and Bulovka Hospital, Prague, Czech Republic.
authors: Pavel
authors: P
authors: Dungl
authors: Department of Radiology, Homolka Hospital, Prague, Czech Republic.
authors: Martin
authors: M
authors: Horak
authors: Faculty of Medicine 1, Charles University and Institute of Rheumatology, Prague, Czech Republic.
authors: Jan J
authors: JJ
authors: Stepan
authors: BOTNAR Research Institute, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences University of Oxford, UK.
authors: Jonathan
authors: J
authors: Reeve
authors: Department of Engineering, University of Cambridge, Cambridge, UK.
authors: Graham M
authors: GM
authors: Treece
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001706:Biopsy; D000071538:Cortical Bone / Q000473:pathology; D005260:Female; D005272:Femur Neck / Q000473:pathology; D006620:Hip Fractures / Q000209:etiology* / Q000473:pathology; D006801:Humans; D008297:Male; D016017:Odds Ratio; D010024:Osteoporosis / Q000150:complications* / Q000473:pathology; D012372:ROC Curve
keywords: Fracture prediction; Hip fracture; Osteoporosis; Pathogenesis