Differences in biomarkers of type II collagen in atrophic and hypertrophic osteoarthritis of the hip: implications for the differing pathobiologies.
BACKGROUND
Cartilage destruction in osteoarthritis (OA) involves the excessive degradation and increased synthesis of cartilage matrix macromolecules including type II collagen (CII) and proteoglycans. The lack of osteophytes (atrophic form of OA) has been shown to be a disease severity factor in hip OA. Since osteophyte formation involves endochondral ossification and a cartilage intermediate, atrophic OA may also exhibit differences in cartilage turnover compared to hypertrophic OA. Cartilage serum biomarkers may offer an opportunity to identify such differences in patients.


OBJECTIVE
To determine whether serum levels of cartilage biomarkers can distinguish between the presence and absence of osteophyte formation in patients with atrophic and hypertrophic hip OA.


METHODS
Fifty-six patients (mean age/standard deviation (SD): 62/11; mean body mass index (BMI)/SD: 27/11) with symptomatic hip OA (American College of Rheumatology criteria; mean Lequesne index/SD: 8.3/4) were classified as having an atrophic or hypertrophic form of OA, according to the absence or presence, respectively, of any osteophyte on a standard radiograph of the pelvis. Minimum joint space width (minJSW) and angles of dysplasia [centre-edge (CE) and head-neck-shaft (HNS)] were determined by computerized measurements. The following serum markers were used which are commercial kits from Ibex Diagnostics (Montreal, QC): proteoglycan aggrecans turnover: CS 846; CII synthesis: C-propeptide (CPII), cleavage by collagenase of type II (C2C) and type I and II (C1,2C) collagens.


METHODS
Patients with atrophic and hypertrophic OA were compared for each variable and step to step logistic regression was used to determine the effect of variables on the belonging to each group. Correlations were examined using linear regression or Spearman test.


RESULTS
CPII serum levels were significantly lower in the atrophic OA patients (77.3 vs 117.4 ng/mL). There were no significant differences between groups for C2C, C1,2C and CS 846 . CPII and C2C concentrations were highly correlated in hypertrophic OA (P=0.002) but not in atrophic OA (P=0.8).


CONCLUSIONS
Atrophic hip OA is characterized by reduced synthetic activity involving type II collagen synthesis. This could account in part for the absence of osteophyte formation. The highly significant correlation between CPII and C2C in hypertrophic but not in atrophic OA suggests that the physiological coupling between CII formation and degradation may be lost in atrophic OA. These differences may therefore help explain the absence of osteophyte in atrophic OA and its association with more rapid disease progression.
Conrozier
T
T
Department of Rheumatology, University Hospital Lyon-sud, Lyon, France. thierry.conrozier@chu-lyon.fr
Ferrand
F
F
Poole
A R
AR
Verret
C
C
Mathieu
P
P
Ionescu
M
M
Vincent
F
F
Piperno
M
M
Spiegel
A
A
Vignon
E
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis*; D024043:Collagen Type II / Q000032:analysis*; D003430:Cross-Sectional Studies; D005260:Female; D006621:Hip Joint / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000473:pathology*; D011446:Prospective Studies
D015415:Biomarkers; D024043:Collagen Type II