Relationships between biochemical markers of bone and cartilage degradation with radiological progression in patients with knee osteoarthritis receiving risedronate: the Knee Osteoarthritis Structural Arthritis randomized clinical trial.
OBJECTIVE
To investigate whether early changes in biochemical markers of bone (NTX-I) and cartilage (CTX-II [C-terminal crosslinking telopeptide of type II collagen]) degradation are associated with radiological progression in patients with knee osteoarthritis (OA) receiving risedronate.


METHODS
Two thousand four hundred and eighty three patients with medial compartment knee OA were randomized in two 24-month studies in North America (NA) and European Union (EU). Studies evaluated risedronate 5 mg/day, 35 mg/week (EU), 50 mg/week (NA), and 15 mg/day (NA and EU), compared to placebo in reducing signs and symptoms and in slowing radiographic progression. One thousand eight hundred and eighty five patients from the pooled EU and NA studies with available NTX-I/CTX-II at both baseline and 6 months and radiographs at baseline and at 24 months were analyzed.


RESULTS
Risedronate produced a dose-dependent reduction of NTX-I and CTX-II observed at 6 months which continued up to 24 months. Patients who had CTX-II levels returned to low levels (<150 ng/mmol creatinine) at 6 months had a lower risk of radiographic progression at 24 months than patients whose CTX-II levels were increased both at baseline and 6 months [odds-ratio (95% confidence interval): 0.57 (0.39-0.85) after adjustment for demographics and joint space width]. The lowest risk of progression was observed in patients who had low CTX-II levels both at baseline and at 6 months [odds-ratio 0.36 (0.21-0.63)]. No significant association between NTX-I levels and radiological progression was observed.


CONCLUSIONS
CTX-II decreased with risedronate in patients with knee OA and levels reached after 6 months were associated with radiological progression at 24 months. Monitoring a marker of cartilage degradation 6 months after initiating treatment may be instructive in identifying patients with low progression.
Garnero
P
P
INSERM Research Unit 664, Lyon, France. patrick.garnero@synarc.com
Aronstein
W S
WS
Cohen
S B
SB
Conaghan
P G
PG
Cline
G A
GA
Christiansen
C
C
Beary
J F
JF
Meyer
J M
JM
Bingham
C O
CO
D000368:Aged; D015415:Biomarkers / Q000652:urine; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001862:Bone Resorption / Q000517:prevention & control / Q000652:urine; D002358:Cartilage, Articular / Q000378:metabolism; D024042:Collagen Type I / Q000652:urine; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000652:urine; D010455:Peptides / Q000652:urine; D011859:Radiography; D000068296:Risedronic Acid
D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000068296:Risedronic Acid; D012968:Etidronic Acid