title: Inhibition of osteoclasts does not prevent joint ankylosis in a mouse model of spondyloarthritis.
abstract: OBJECTIVE
  The relationship between inflammation, destruction and new tissue formation leading to ankylosis, determines the severity and prognosis of patients with SpA. Recent data in mice and men suggest that new cartilage and bone formation and subsequent ankylosis are uncoupled from chronic inflammation. These data challenge the hypothesis that inflammation and tissue damage trigger an excessive repair response in SpA. We tested whether inhibition of bone erosion by targeting osteoclasts, would prevent or influence joint ankylosis in a mouse model.
  
  
  METHODS
  Male DBA/1 mice from different litters were caged together at the age of 8 weeks. Treatment with zoledronic acid (ZA) (100 ng/g) or placebo was started at the age of 10 weeks and administered every 2 weeks. Clinical incidence and severity of arthritis were evaluated twice a week until the age of 26 weeks. At this point, bone density measurements were performed, mice were sacrificed and severity of arthritis was evaluated by histology.
  
  
  RESULTS
  Treatment with ZA did not affect incidence or clinical severity of arthritis in male DBA/1 mice. ZA treatment significantly increased bone mineral density and content as demonstrated by dual X-ray densitometry and peripheral quantitative CT. However, the treatment did not affect histomorphological appearance of arthritis or ankylosis.
  
  
  CONCLUSIONS
  These data suggest that bone erosion at the enthesis does not necessarily precede entheseal ankylosis. Therefore, these observations further support the concept that inflammation and new tissue formation in SpA are at least partially uncoupled events and may be different therapeutic targets.
authors.affiliation: Division of Rheumatology, Department of Musculoskeletal Sciences, Katholieke Universiteit Leuven, Leuven, Belgium. Rik.Lories@uz.kuleuven.be
authors.forename: R J U
authors.initials: RJ
authors.lastname: Lories
authors.forename: I
authors.initials: I
authors.lastname: Derese
authors.forename: F P
authors.initials: FP
authors.lastname: Luyten
mesh_terms: D000818:Animals; D000844:Ankylosis / Q000473:pathology; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007093:Imidazoles / Q000627:therapeutic use*; D007596:Joints / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology*; D025241:Spondylarthritis / Q000188:drug therapy*; D017211:Treatment Failure; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid