title: Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: results of the two-year multinational knee osteoarthritis structural arthritis study.
abstract: OBJECTIVE
  Bisphosphonates have slowed the progression of osteoarthritis (OA) in animal models and have decreased pain in states of high bone turnover. The Knee OA Structural Arthritis (KOSTAR) study, which is the largest study to date investigating a potential structure-modifying OA drug, tested the efficacy of risedronate in providing symptom relief and slowing disease progression in patients with knee OA.
  
  
  METHODS
  The study group comprised 2,483 patients with medial compartment knee OA and 2-4 mm of joint space width (JSW), as determined using fluoroscopically positioned, semiflexed-view radiography. Patients were enrolled in 2 parallel 2-year studies in North America and the European Union. These studies evaluated the efficacy of risedronate at dosages of 5 mg/day, 15 mg/day, 35 mg/week (in Europe), and 50 mg/week (in North America) compared with placebo in reducing signs and symptoms, as measured by the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and patient global assessment (PGA) scores, and in slowing radiographic progression.
  
  
  RESULTS
  A reduction of approximately 20% in signs and symptoms, as measured by WOMAC subscales and PGA scores, was observed in all groups, with no treatment effect of risedronate demonstrated. Risedronate did not significantly reduce radiographic progression as measured by decreased JSW or using a dichotomous definition of progression (joint space loss of >or=0.6 mm). Thirteen percent of patients receiving placebo demonstrated significant disease progression over 2 years. A dose-dependent reduction in the level of C-terminal crosslinking telopeptide of type II collagen, a cartilage degradation marker associated with progressive OA, was seen in patients who received risedronate. No increase in the number of adverse events was demonstrated for risedronate compared with placebo.
  
  
  CONCLUSIONS
  Although risedronate (compared with placebo) did not improve signs or symptoms of OA, nor did it alter progression of OA, a reduction in the level of a marker of cartilage degradation was observed. A sustained clinically relevant improvement in signs and symptoms was observed in all treatment and placebo groups.
authors.affiliation: Division of Rheumatology, Johns Hopkins University, 5200 Eastern Avenue, Mason F. Lord Building, Center Tower, Room 404, Baltimore, MD 21224, USA. Clifton.bingham@jhmi.edu
authors.forename: Clifton O
authors.initials: CO
authors.lastname: Bingham
authors.forename: J Chris
authors.initials: JC
authors.lastname: Buckland-Wright
authors.forename: Patrick
authors.initials: P
authors.lastname: Garnero
authors.forename: Stanley B
authors.initials: SB
authors.lastname: Cohen
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
authors.forename: Silvano
authors.initials: S
authors.lastname: Adami
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Clauw
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pelletier
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Raynauld
authors.forename: Vibeke
authors.initials: V
authors.lastname: Strand
authors.forename: Lee S
authors.initials: LS
authors.lastname: Simon
authors.forename: Joan M
authors.initials: JM
authors.lastname: Meyer
authors.forename: Gary A
authors.initials: GA
authors.lastname: Cline
authors.forename: John F
authors.initials: JF
authors.lastname: Beary
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D002356:Cartilage / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D018450:Disease Progression; D012968:Etidronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D010146:Pain / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D010919:Placebos; D011859:Radiography; D000068296:Risedronic Acid; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D010919:Placebos; D000068296:Risedronic Acid; D012968:Etidronic Acid