title: Improving subchondral bone integrity reduces progression of cartilage damage in experimental osteoarthritis preceded by osteoporosis.
abstract: OBJECTIVE
  Impairment of subchondral bone density and quality aggravates cartilage damage in osteoarthritis (OA). Accordingly, we assessed whether improving microstructure and quality at subchondral bone by the bone-forming agent parathyroid hormone (PTH) [1-34] prevent cartilage damage progression in a rabbit model of OA preceded by osteoporosis (OP).
  
  
  METHODS
  OP was induced in 20 female rabbits. At week 7, these rabbits underwent knee surgery to induce OA and, at week 12, they started either saline vehicle (n=10) or PTH (n=10) for 10 weeks. Ten healthy animals were used as controls. At week 22, microstructure was assessed by micro-computed tomography and bone remodelling by protein expression of alkaline phosphatase (ALP), metalloproteinase-9 (MMP9), osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) at subchondral bone. Cartilage damage was evaluated using Mankin score.
  
  
  RESULTS
  PTH reversed the decrease of bone area/tissue area, trabecular thickness, plate thickness, polar moment of inertia, ALP expression and OPG/RANKL ratio, as well as counteracted the increase of fractal dimension and MMP9 expression at subchondral bone of osteoarthritis preceded by osteoporosis (OPOA) rabbits compared to vehicle administration (P<0.05). Likewise, PTH decreased cartilage damage severity in OPOA rabbits. Good correlations were observed between subchondral bone structure or remodelling parameters, and cartilage Mankin score.
  
  
  CONCLUSIONS
  Improvement of microstructural and remodelling parameters at subchondral bone by PTH [1-34] contributed to prevent cartilage damage progression in rabbits with early OPOA. These findings support the role of subchondral bone in OA. Further studies are warranted to establish the place of bone-forming agents as potential treatment in OA.
authors.affiliation: Bone and Joint Research Unit, Service of Rheumatology, IIS Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain. miriambellido@hotmail.com
authors.forename: M
authors.initials: M
authors.lastname: Bellido
authors.forename: L
authors.initials: L
authors.lastname: Lugo
authors.forename: J A
authors.initials: JA
authors.lastname: Roman-Blas
authors.forename: S
authors.initials: S
authors.lastname: Castañeda
authors.forename: E
authors.initials: E
authors.lastname: Calvo
authors.forename: R
authors.initials: R
authors.lastname: Largo
authors.forename: G
authors.initials: G
authors.lastname: Herrero-Beaumont
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects*; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000378:metabolism / Q000648:ultrastructure*; D016022:Case-Control Studies; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006614:Hindlimb / Q000000981:diagnostic imaging / Q000378:metabolism / Q000648:ultrastructure; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism; D010024:Osteoporosis / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D053245:RANK Ligand / Q000378:metabolism; D011817:Rabbits; D055114:X-Ray Microtomography
chemical_list: D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand; D000469:Alkaline Phosphatase; D020780:Matrix Metalloproteinase 9