Urinary 4-pyridoxic acid as a non-invasive biomarker for evaluating osteoarthritis severity: findings from the ROAD study

  • Aging Clin Exp Res. 2025 Feb 25;37(1):50. doi: 10.1007/s40520-025-02944-6.
Noriko Yoshimura  1 ,  Aiko Miyazaki  2 ,  Toshiko Iidaka  3 ,  Nobuo Ando  2 ,  Gaku Tanegashima  4 ,  Shigeyuki Muraki  3 ,  Horiyuki Oka  5 ,  Sakae Tanaka  4
Affiliations
  • 1. Department of Preventive Medicine for Locomotive Organ Disorders, 22ndMedical and Research Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan. [email protected].
  • 2. Fushimi Pharmaceutical Co., Ltd, Marugame, Kagawa Prefecture, Japan.
  • 3. Department of Preventive Medicine for Locomotive Organ Disorders, 22ndMedical and Research Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
  • 4. Department of Orthopaedic Surgery, The University of Tokyo, Tokyo, Japan.
  • 5. Division of Musculoskeletal AI System Development, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
PMID: 40000531 DOI: 10.1007/s40520-025-02944-6
Abstract

Background: The early detection of osteoarthritis (OA) requires reliable biomarkers; however, reports identifying such biomarkers remain limited.

Aims: This study aimed to evaluate the potential of urinary 4-pyridoxic acid (4PA) as a biomarker for the severity of knee osteoarthritis (KOA) and lumbar spondylosis (LS) in Japanese adults, using data from the population-based cohort study.

Methods: Data were analysed from 1566 participants (510 men and 1,056 women) aged ≥ 40 years, who were enrolled in the Research on Osteoarthritis/Osteoporosis against Disability (ROAD) cohort, a population-based study initiated in 2005. Participants underwent radiographic assessments of the knees and lumbar spine, and urinary 4PA levels were measured using high-performance liquid chromatography. Logistic regression analyses were performed to evaluate the association between urinary 4PA levels and the Kellgren-Lawrence (KL) grade of KOA and LS, adjusting for age, sex, body mass index (BMI), and lifestyle factors.

Results: Urinary 4PA levels were significantly higher in participants with KL grade 4 KOA compared to those with lower KL grades (p < 0.001). This association remained significant after adjusting for confounding factors. In contrast, no significant differences in 4PA levels were observed across the KL grades for LS, although a slight increase in 4PA levels was noted in KL grade 4 cases.

Discussion and conclusions: These findings suggest that urinary 4PA could serve as a biomarker for assessing KOA severity, particularly in advanced stages. While the detection of early OA using 4PA remains challenging, the significant increase in KL grade 4 cases highlights its potential role in guiding treatment decisions, such as surgical intervention.

Keywords
4-pyridoxic acid; Knee osteoarthritis; Lumbar spondylosis; Population-based cohort ROAD; Predictive biomarker.
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