title: Statins and fibrates do not affect development of spontaneous cartilage damage in STR/Ort mice.
abstract: OBJECTIVE
  Since statins and fibrates are capable of improving the metabolic profile of patients as well as decreasing inflammation, they are considered as potential drugs for preventing osteoarthritis (OA). The goal of the present study was to investigate the effect of these drugs in the STR/Ort spontaneous OA mouse model.
  
  
  METHODS
  Male STR/Ort mice received control diet or control diet containing two different dosages of simvastatin or fenofibrate or a combination of both. Mice were euthanized after 16 weeks of treatment at the age of 24 weeks. Serum analysis for metabolic and inflammatory markers, histologic OA grading and micro computed tomography (μCT) analysis of subchondral bone plate were performed.
  
  
  RESULTS
  Simvastatin treatment did not have a statistically significant effect on any of the measured parameters. Fenofibrate treated mice gained less body weight (BW) and had lower serum amyloid A (SAA) levels, but higher Interleukin (IL)-1α and MIP1α than other mice. Mice treated with 200 mg/kg BW/day fenofibrate had less subchondral bone plate volume than control, but no statistically significant reduction in cartilage damage. In the combination treatment group, BW and SAA were lower than control. Overall, bodyweight, synovium membrane cell layers and SAA levels correlated to subchondral bone plate changes and subchondral bone plate changes correlated to cartilage damage.
  
  
  CONCLUSIONS
  Statins and fibrates did not affect development of cartilage damage in the STR/Ort spontaneous OA mouse model. Fenofibrates however, had an effect on BW, serum inflammation markers and subchondral bone plate morphology.
authors.affiliation: Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: w.wei@erasmusmc.nl.
authors.forename: W
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, The Netherlands; Department of Orthopaedics, University of Antwerp, Antwerp, Belgium. Electronic address: stefan.clockaerts@ua.ac.be.
authors.forename: S
authors.initials: S
authors.lastname: Clockaerts
authors.affiliation: Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: y.bastiaansen@erasmusmc.nl.
authors.forename: Y M
authors.initials: YM
authors.lastname: Bastiaansen-Jenniskens
authors.affiliation: TNO, Leiden, The Netherlands; Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: lobke.gierman@tno.nl.
authors.forename: L M
authors.initials: LM
authors.lastname: Gierman
authors.affiliation: Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, Zurich, Switzerland. Electronic address: smbotter@hotmail.com.
authors.forename: S M
authors.initials: SM
authors.lastname: Botter
authors.affiliation: Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, The Netherlands; Department of General Practice, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: s.bierma-zeinstra@erasmusmc.nl.
authors.forename: S M A
authors.initials: SM
authors.lastname: Bierma-Zeinstra
authors.affiliation: Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, The Netherlands; Department of Biomechanical Engineering, Delft University of Technology, Delft, The Netherlands; Department of Orthopaedics, Utrecht University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: h.weinans@erasmusmc.nl.
authors.forename: H
authors.initials: H
authors.lastname: Weinans
authors.affiliation: Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: j.verhaar@erasmusmc.nl.
authors.forename: J A N
authors.initials: JA
authors.lastname: Verhaar
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: g.kloppenburg@lumc.nl.
authors.forename: M
authors.initials: M
authors.lastname: Kloppenburg
authors.affiliation: TNO, Leiden, The Netherlands. Electronic address: anne-marie.zuurmond@tno.nl.
authors.forename: A-M
authors.initials: AM
authors.lastname: Zuurmond
authors.affiliation: Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, The Netherlands; Department of Otorhinolaryngology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: g.vanosch@erasmusmc.nl.
authors.forename: G J V M
authors.initials: GJ
authors.lastname: van Osch
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002358:Cartilage, Articular / Q000473:pathology; D004032:Diet; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004359:Drug Therapy, Combination; D011345:Fenofibrate / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010003:Osteoarthritis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D019821:Simvastatin / Q000627:therapeutic use*; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D018836:Inflammation Mediators; D019821:Simvastatin; D011345:Fenofibrate
keywords: Cartilage; Mouse; Osteoarthritis; Subchondral bone; Therapy pharmacological