title: Bone marrow abnormalities on magnetic resonance imaging are associated with type II collagen degradation in knee osteoarthritis: a three-month longitudinal study.
abstract: OBJECTIVE
  Using radiography to assess the efficacy of a disease-modifying osteoarthritis (OA) drug on joint structure is challenging. Subchondral bone marrow abnormalities determined by magnetic resonance imaging (MRI) and urinary excretion of C-terminal crosslinking telopeptide of type II collagen (CTX-II) have recently been shown to be predictors of radiographic progression in patients with knee OA, suggesting that these may represent valuable biomarkers with increased sensitivity compared with findings on radiography. The aims of this investigation were to analyze, in patients with knee OA, whether the values associated with these 2 OA biomarkers can change within 3 months, and to investigate the relationships between bone marrow abnormalities and CTX-II.
  
  
  METHODS
  Knee MRI scans were obtained in 377 patients with painful knee OA (76% women, mean age 63 years, mean disease duration 6.6 years) at both baseline and 3 months. The femoral and tibial condyles and the patella were divided into 8 sites for the scoring of bone marrow abnormalities. A bone marrow abnormality was defined as an area of increased signal on T2-weighted images of the subchondral bone. All scans were reviewed centrally and scored by a single trained radiologist using a validated 4-point scoring method. Fasting urine and serum samples were also collected from all patients at baseline, month 1, month 2, and month 3, in order to measure the levels of urinary CTX-II and serum CTX-I, a biochemical marker of bone resorption.
  
  
  RESULTS
  At baseline, 82% of patients had MRI evidence of bone marrow abnormalities. Bone marrow abnormality scores correlated significantly with CTX-II levels (P < 0.0001). Within 3 months, the bone marrow abnormality score decreased in 37 patients (9.8%), increased in 71 patients (18.8%), and did not change in the majority of patients (71.4%). Patients with baseline urinary CTX-II levels in the highest tertile had a relative risk of 2.4 (95% confidence interval 1.1-5.0) of worsening bone marrow abnormalities at 3 months compared with patients with levels in the lowest tertile, after adjustment for age, sex, and body mass index. In patients who showed a decrease in the bone marrow abnormality score at 3 months, urinary CTX-II levels decreased significantly (mean -75 ng/mmole creatinine), whereas levels increased (mean +23 ng/mmole creatinine) in patients showing an increase in the bone marrow abnormality score (P = 0.01 between the 2 groups). No significant association between bone marrow abnormalities and serum CTX-I was observed.
  
  
  CONCLUSIONS
  In patients with painful knee OA, bone marrow abnormalities on MRI can change within only 3 months in approximately 30% of patients. Reduction in the extent of bone marrow abnormalities is associated with a decrease in cartilage degradation.
authors.affiliation: Synarc, Lyon, France. Patrick.Garnero@synarc.com
authors.forename: P
authors.initials: P
authors.lastname: Garnero
authors.forename: C
authors.initials: C
authors.lastname: Peterfy
authors.forename: S
authors.initials: S
authors.lastname: Zaim
authors.forename: M
authors.initials: M
authors.lastname: Schoenharting
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D024043:Collagen Type II / Q000378:metabolism*; D005260:Female; D005269:Femur / Q000473:pathology; D006801:Humans; D007391:International Cooperation; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology; D010147:Pain Measurement; D010329:Patella / Q000473:pathology; D010455:Peptides / Q000097:blood; D011859:Radiography; D012720:Severity of Illness Index; D013977:Tibia / Q000473:pathology
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D024043:Collagen Type II; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen