Relationships between biomarkers of cartilage, bone, synovial metabolism and knee pain provide insights into the origins of pain in early knee osteoarthritis

Muneaki Ishijima,Robin A Poole,Isao Nagaoka,Kiyohito Naito,Hisashi Kurosawa,Haruka Kaneko,Hideyo Yamaguchi,Akihito Tomonaga,Kazuo Kaneko,Taiji Watari,Ippei Futami,Tetsuro Yamamoto,Kaori Yoshimura-Ishida

doi:10.1186/ar3246

Abstract

IntroductionWe tested the hypothesis that there exist relationships between the onset of early stage radiographically defined knee osteoarthritis (OA), pain and changes in biomarkers of joint metabolism.MethodsUsing Kellgren-Lawrence (K/L) grading early radiographic knee OA (K/L 2) was detected in 16 of 46 patients. These grades (K/L 1 is no OA and K/L 2 is early OA) were divided into two groups according to the presence or absence of persistent knee pain. Sera (s) and urines (u) were analysed with biomarkers for cartilage collagen cleavage (sC2C and uCTX-II) and synthesis (sCPII), bone resorption (uNTx) and synovitis (hyaluronic acid: sHA).ResultssCPII decreased and sC2C/sCPII, uCTX-II/sCPII and sHA increased with onset of OA (K/L 2 versus K/L 1) irrespective of joint pain. In contrast, sC2C and uCTX-II remained unchanged in early OA patients. Of the patients with K/L grades 1 and 2 sC2C, sCPII, sHA, uNTX and uCTX-II were all significantly increased in patients with knee pain independent of grade. Among the K/L grade 2 subjects, only uCTX-II and uCTX-II/sCPII were increased in those with knee pain. In grade 1 patients both sC2C and sCPII were increased in those with knee pain. No such grade specific changes were seen for the other biomarkers including sHA.ConclusionsThese results suggest that changes in cartilage matrix turnover detected by molecular biomarkers may reflect early changes in cartilage structure that account directly or indirectly for knee pain. Also K/L grade 1 patients with knee pain exhibit biomarker features of early OA.

Highlights

We tested the hypothesis that there exist relationships between the onset of early stage radiographically defined knee osteoarthritis (OA), pain and changes in biomarkers of joint metabolism
There were no significant differences for the cartilage collagen degradation markers sC2C and uCTX-cartilage type II procollagen carboxy propeptide (II) between K/L grade 1 and grade 2. sCPII, a cartilage collagen synthesis marker, was significantly reduced in K/L grade 2 compared to grade 1
Both sC2C/sCPII and uCTX-II/sCPII were significantly increased in K/L grade 2 compared to grade 1 reflecting alterations in the balance between synthesis and degradation

Summary

Introduction

We tested the hypothesis that there exist relationships between the onset of early stage radiographically defined knee osteoarthritis (OA), pain and changes in biomarkers of joint metabolism. Pain is the most prominent and disabling symptom of knee osteoarthritis (OA) and is an increasingly important public health problem [1,2,3,4]. Pain is the major reason why individuals seek medical attention from early-through end-stage knee OA, the treatment of which in advanced disease commonly includes joint replacement. Pain is a major determinant for the loss of joint function. The gold standard for assessing joint damage is still the plain radiograph. This method only provides a historical view of the skeletal damage that has already occurred. Often weak associations have been reported between pain and radiographic change [6]

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Conclusion