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Different changes in the biomarker C-terminal telopeptides of type II collagen (CTX-II) following intra-articular injection of high molecular weight hyaluronic acid and oral non-steroidal anti-inflammatory drugs in patients with knee osteoarthritis: a multi-center randomized controlled study.

Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: ishijima@juntendo.ac.jp. Department of Orthopaedic Surgery, University of Occupational and Environmental Health, Fukuoka, Japan. Electronic address: t-nak@utopia.ocn.ne.jp. Department of Orthopaedic Surgery, Gifu University, School of Medicine, Gifu, Japan. Electronic address: dn4k-smz@asahi-net.or.jp. Department of Laboratory Sciences, School of Health Sciences, Faculty of Medicine, Gunma University, Gunma, Japan. Electronic address: khayashi@gunma-u.ac.jp. Department of Orthopaedic Surgery, Kinki University Sakai Hospital, Osaka, Japan. Electronic address: kikuchi@sakaisakibana.jp. Department of Orthopaedic Surgery and Rheumatology, Nara Hospital, Kinki University Faculty of Medicine, Ikoma, Japan; Department of Laboratory Sciences, School of Health Sciences, Faculty of Medicine, Gunma University, Gunma, Japan. Electronic address: nra48207@nifty.com. Center of Transdisciplinary Research, Institute for Research Promotion, Niigata University, Niigata, Japan. Electronic address: omori@nuhw.ac.jp. Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Hokkaido, Japan. Electronic address: tyamasit@sapmed.ac.jp. Department of Orthopaedic Surgery, Faculty of Medicine, Shimane University School of Medicine, Shimane, Japan. Electronic address: uchio@med.shimane-u.ac.jp. Department of Orthopaedic Surgery, Tokyo Women's Medical University, Medical Center East, Tokyo, Japan. Electronic address: chiba.junji@twmu.ac.jp. Center of Mathematics and Data Sciences, Gunma University, Maebashi, Japan. Electronic address: y-ideno@gunma-u.ac.jp. Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: mkubota@juntendo.ac.jp. Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: harukago@juntendo.ac.jp. Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: kuro@koto-hospital.or.jp. Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: k-kaneko@juntendo.ac.jp.

Osteoarthritis and cartilage. 2022;(6):852-861
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Abstract

OBJECTIVES We previously reported, based on a multicenter randomized-control study, that the efficacy of intra-articular injections of hyaluronic acid (IA-HA) was not inferior to that of oral non-steroidal anti-inflammatory drugs (NSAIDs) in patients with knee osteoarthritis (OA). However, the molecular effects on the pathophysiology of knee OA remain unclear. C-terminal telopeptides of type II collagen (CTX-II) is reported to primarily originate from the interface between articular cartilage and subchondral bone, which is a site of potential remodeling in OA. We performed a predefined sub-analysis of the previous study to compare the changes of urinary CTX-II (uCTX-II) in response to IA-HA to those in response to NSAID for knee OA. DESIGN A total of 200 knee OA patients were registered from 20 hospitals and randomized to receive IA-HA (2,700 kDa HA, 5 times at 1-week intervals) or NSAID (loxoprofen sodium, 180 mg/day) for 5 weeks. The uCTX-II levels were measured before and after treatment. RESULTS The uCTX-II levels were significantly increased by IA-HA treatment (337.7 ± 193.8 to 370.7 ± 234.8 ng/μmol Cr) and were significantly reduced by NSAID treatment (423.2 ± 257.6 to 370.3 ± 250.9 ng/μmol Cr). The %changes of uCTX-II induced by IA-HA (11.6 ± 29.5%) and NSAID (-9.0 ± 26.7%) was significantly different (between-group difference: 20.6, 95% confidence intervals: 10.6 to 30.6). CONCLUSIONS While both IA-HA and NSAID improved symptoms of knee OA, uCTX-II levels were increased by IA-HA and reduced by NSAIDs treatment, suggesting these treatments may improve symptoms of knee OA through different modes of action.

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