title: Serum hyaluronic acid concentration predicts the progression of joint space narrowing in normal knees and established knee osteoarthritis - a five-year prospective cohort study.
abstract: BACKGROUND
  Serum hyaluronic acid (sHA) is a serum biomarker for knee osteoarthritis (OA). Although sHA concentration is elevated in patients with knee OA, the relationship between serum concentration and disease progression remains unclear. We examined the relationship between sHA concentration and radiographic progression of knee OA in a cohort of individuals followed for 5 years.
  
  
  METHODS
  We prospectively enrolled 444 individuals and measured their sHA concentrations at baseline. Anterior-posterior weight bearing knee radiographs were obtained at baseline and the 5-year endpoint. Osteoarthritic knee changes were classified according to Kellgren-Lawrence (KL) grade, and joint space narrowing (JSN) was measured using a Knee Osteoarthritis Computer-Aided Diagnosis (KOACAD) system. Correlations between sHA concentration, progression in KL grade, and JSN were assessed using regression models, taking into account potentially confounding factors.
  
  
  RESULTS
  OA progressed from KL grades 0 or 1 in 129 of the 323 knees, and from KL grades 2 or 3 in 61 of the 119 knees. Higher sHA concentrations were correlated with KL grade progression (p = 0.004). The mean JSN, as assessed by KOACAD over 5 years, was 0.23 ± 0.55 mm, and sHA concentration was positively correlated with progression of JSN in KL grades 0 or 1 (p = 0.021) and KL grades 2 or 3 (p = 0.008) knees.
  
  
  CONCLUSIONS
  Serum HA concentration was positively correlated with progression of KL grade. sHA was also positively correlated with progression of JSN in knees with and without OA, suggesting that sHA concentration may be a useful predictor of knee OA progression.
authors.affiliation: Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan. e_sasaki@hirosaki-u.ac.jp.|Department of Social Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. e_sasaki@hirosaki-u.ac.jp.
authors.forename: Eiji
authors.initials: E
authors.lastname: Sasaki
authors.affiliation: Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan. eiichi@hirosaki-u.ac.jp.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Tsuda
authors.affiliation: Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan. yuji1112@hirosaki-u.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan. s-maeda@hirosaki-u.ac.jp.
authors.forename: Shugo
authors.initials: S
authors.lastname: Maeda
authors.affiliation: Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan. inoueryo@hirosaki-u.ac.jp.
authors.forename: Ryo
authors.initials: R
authors.lastname: Inoue
authors.affiliation: Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan. dachiba@hirosaki-u.ac.jp.|Department of Social Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. dachiba@hirosaki-u.ac.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Chiba
authors.affiliation: Glycoconjugate Research Center, Kurihama Plant, Seikagaku Corporation, Yokosuka, Japan. hiroshi.fujita@seikagaku.co.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujita
authors.affiliation: Department of Social Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. ippei@hirosaki-u.ac.jp.
authors.forename: Ippei
authors.initials: I
authors.lastname: Takahashi
authors.affiliation: Department of Social Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. tume@meijo-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Umeda
authors.affiliation: Department of Social Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. nakaji@hirosaki-u.ac.jp.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Nakaji
authors.affiliation: Department of Orthopaedic Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan. yasuyuki@hirosaki-u.ac.jp.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ishibashi
mesh_terms: D015415:Biomarkers / Q000097:blood*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology*; D011446:Prospective Studies; D011859:Radiography
chemical_list: D015415:Biomarkers; D006820:Hyaluronic Acid