title: Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis.
abstract: BACKGROUND
  Osteoporosis (OP) increases cartilage damage in a combined rabbit model of OP and osteoarthritis (OA). Accordingly, we assessed whether microstructure impairment at subchondral bone aggravates cartilage damage in this experimental model.
  
  
  METHODS
  OP was induced in 20 female rabbits, by ovariectomy and intramuscular injections of methylprednisolone hemisuccinate for four weeks. Ten healthy animals were used as controls. At week 7, OA was surgically induced in left knees of all rabbits. At 22 weeks, after sacrifice, microstructure parameters were assessed by micro-computed tomography, and osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), alkaline phosphatase (ALP) and metalloproteinase 9 (MMP9) protein expressions were evaluated by Western Blot at subchondral bone. In addition, cartilage damage was estimated using the histopathological Mankin score. Mann-Whitney and Spearman statistical tests were performed as appropriate, using SPSS software v 11.0. Significant difference was established at P < 0.05.
  
  
  RESULTS
  Subchondral bone area/tissue area, trabecular thickness and polar moment of inertia were diminished in OPOA knees compared with control or OA knees (P < 0.05). A decrease of plate thickness, ALP expression and OPG/RANKL ratio as well as an increased fractal dimension and MMP9 expression occurred at subchondral bone of OA, OP and OPOA knees vs. controls (P < 0.05). In addition, the severity of cartilage damage was increased in OPOA knees vs. controls (P < 0.05). Remarkably, good correlations were observed between structural and remodelling parameters at subchondral bone, and furthermore, between subchondral structural parameters and cartilage Mankin score.
  
  
  CONCLUSIONS
  Microstructure impairment at subchondral bone associated with an increased remodelling aggravated cartilage damage in OA rabbits with previous OP. Our results suggest that an increased subchondral bone resorption may account for the exacerbation of cartilage damage when early OA and OP coexist simultaneously in same individuals.
authors.affiliation: Service of Rheumatology, Fundación Jiménez Díaz, Universidad Autónoma, Avda, Reyes Católicos, 2, 28040 Madrid, Spain. miriambellido@hotmail.com
authors.forename: Miriam
authors.initials: M
authors.lastname: Bellido
authors.forename: Laura
authors.initials: L
authors.lastname: Lugo
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Roman-Blas
authors.forename: Santos
authors.initials: S
authors.lastname: Castañeda
authors.forename: Jose R
authors.initials: JR
authors.lastname: Caeiro
authors.forename: Sonia
authors.initials: S
authors.lastname: Dapia
authors.forename: Emilio
authors.initials: E
authors.lastname: Calvo
authors.forename: Raquel
authors.initials: R
authors.lastname: Largo
authors.forename: Gabriel
authors.initials: G
authors.lastname: Herrero-Beaumont
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002356:Cartilage / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D005260:Female; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010003:Osteoarthritis / Q000150:complications* / Q000000981:diagnostic imaging* / Q000378:metabolism; D010024:Osteoporosis / Q000150:complications* / Q000000981:diagnostic imaging* / Q000378:metabolism; D010052:Ovariectomy; D011817:Rabbits; D055114:X-Ray Microtomography
chemical_list: D000469:Alkaline Phosphatase; D020780:Matrix Metalloproteinase 9