title: Chronic arthritis leads to disturbances in the bone collagen network.
abstract: BACKGROUND
  In this study we used a mice model of chronic arthritis to evaluate if bone fragility induced by chronic inflammation is associated with an imbalance in bone turnover and also a disorganization of the bone type I collagen network.
  
  
  METHODS
  Serum, vertebrae and femur bones were collected from eight-month-old polyarthritis SKG mice and controls. Strength of the femoral bones was evaluated using three-point bending tests and density was assessed with a pycnometer. Bone turnover markers carboxy-terminal collagen cross-linking telopeptides (CTX-I) and amino-terminal propeptide of type I procollagen (PINP) were measured in serum. The organization and density of bone collagen were analyzed in vertebrae using second-harmonic generation (SHG) imaging with a two-photon microscope and trabecular bone microstructure was assessed by scanning electron microscope (SEM).
  
  
  RESULTS
  Femoral bones of SKG mice revealed increased fragility expressed by deterioration of mechanical properties, namely altered stiffness (P = 0.007) and reduced strength (P = 0.006), when compared to controls. Accordingly, inter-trabecular distance and trabecular thickness as observed by SEM were reduced in SKG mice. PINP was significantly higher in arthritic mice (9.18 +/- 3.21 ng/ml) when compared to controls (1.71 +/- 0.53 ng/ml, P < 0.001). Bone resorption marker CTX-I was 9.67 +/- 3.18 ng/ml in arthritic SKG mice compared to 6.23 +/- 4.11 ng/ml in controls (P = 0.176). The forward-to-backward signal ratio measured by SHG was higher in SKG animals, reflecting disorganized matrix and loose collagen structure, compared to controls.
  
  
  CONCLUSIONS
  We have shown for the first time that chronic arthritis by itself impairs bone matrix architecture, probably due to disturbed bone remodeling and increased collagen turnover. This effect might predispose patients to bone fragility fractures.
authors.affiliation: Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisbon, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Caetano-Lopes
authors.forename: Ana M
authors.initials: AM
authors.lastname: Nery
authors.forename: Helena
authors.initials: H
authors.lastname: Canhão
authors.forename: Joana
authors.initials: J
authors.lastname: Duarte
authors.forename: Rita
authors.initials: R
authors.lastname: Cascão
authors.forename: Ana
authors.initials: A
authors.lastname: Rodrigues
authors.forename: Inês P
authors.initials: IP
authors.lastname: Perpétuo
authors.forename: Saba
authors.initials: S
authors.lastname: Abdulghani
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Amaral
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
authors.forename: Luís
authors.initials: L
authors.lastname: Graça
authors.forename: Maria F
authors.initials: MF
authors.lastname: Vaz
authors.forename: João E
authors.initials: JE
authors.lastname: Fonseca
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology*; D001696:Biomechanical Phenomena; D015519:Bone Density; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology*; D002908:Chronic Disease; D024042:Collagen Type I / Q000097:blood / Q000378:metabolism*; D005260:Female; D005269:Femur / Q000378:metabolism / Q000473:pathology; D008159:Lumbar Vertebrae / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood
chemical_list: D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide