Objectives To explore the association between serum vitamin D levels and the risk of knee and hip osteoarthritis (KOA and HOA). Methods This study included 295,557 participants (mean 56 years, 53% female) from the UK Biobank who had data on serum vitamin D levels and did not have KOA or HOA at baseline. The associations between serum vitamin D levels and the incidences of KOA and HOA were evaluated using Cox regression models. Mediating effects of serum biomarkers of inflammation (IL-1a, IL-1b, IL-6, and TNF) and cartilage metabolism (COMP, CRTAC1, and COL9A1) were explored. Results During a median follow-up of 13.1 years, 12,266 (4.2%) and 8931 (3.0%) participants developed KOA and HOA, respectively. Serum vitamin D levels were positively associated with osteoarthritis risk (KOA—hazard ratio [HR] = 1.14, 95% confidence interval [CI] 1.12–1.17; HOA—HR = 1.09, 95% CI 1.06–1.12). Compared to participants with severe vitamin D deficiency (< 25 nmol/L), those with sufficient vitamin D levels (≥ 75 nmol/L) had a 55% and 30% higher risk of developing KOA and HOA, respectively. Cartilage metabolism markers, but not inflammation markers, mediated 5.6%–12.6% of the associations between serum vitamin D levels and KOA risk. Conclusion High serum vitamin D levels are associated with an increased risk of OA in middle-aged and older adults. While serum vitamin D has recognized benefits for bone and cardiovascular health, these findings highlight a potential association with osteoarthritis risk without suggesting a causal effect.<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> Key Points • High vitamin D levels increase osteoarthritis risk. • Cartilage metabolism partially mediates this association. • Inflammatory markers show no mediating effect. </entry> </row> </tbody> </tgroup> </Table>

Cartilage metabolism mediates the association between serum vitamin D levels and the risk of osteoarthritis: a prospective cohort study from the UK Biobank

期刊论文
发表日期：

2026年2月16日

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Junjie Wang,
Xusheng Cheng,
Jianqiao Wang,
Jingyi Yin,
Xing Xing,
Guoqi Cai

摘要

Objectives

To explore the association between serum vitamin D levels and the risk of knee and hip osteoarthritis (KOA and HOA).

Methods

This study included 295,557 participants (mean 56 years, 53% female) from the UK Biobank who had data on serum vitamin D levels and did not have KOA or HOA at baseline. The associations between serum vitamin D levels and the incidences of KOA and HOA were evaluated using Cox regression models. Mediating effects of serum biomarkers of inflammation (IL-1a, IL-1b, IL-6, and TNF) and cartilage metabolism (COMP, CRTAC1, and COL9A1) were explored.

Results

During a median follow-up of 13.1 years, 12,266 (4.2%) and 8931 (3.0%) participants developed KOA and HOA, respectively. Serum vitamin D levels were positively associated with osteoarthritis risk (KOA—hazard ratio [HR] = 1.14, 95% confidence interval [CI] 1.12–1.17; HOA—HR = 1.09, 95% CI 1.06–1.12). Compared to participants with severe vitamin D deficiency (< 25 nmol/L), those with sufficient vitamin D levels (≥ 75 nmol/L) had a 55% and 30% higher risk of developing KOA and HOA, respectively. Cartilage metabolism markers, but not inflammation markers, mediated 5.6%–12.6% of the associations between serum vitamin D levels and KOA risk.

Conclusion

High serum vitamin D levels are associated with an increased risk of OA in middle-aged and older adults. While serum vitamin D has recognized benefits for bone and cardiovascular health, these findings highlight a potential association with osteoarthritis risk without suggesting a causal effect.

Key Points

• High vitamin D levels increase osteoarthritis risk.

• Cartilage metabolism partially mediates this association.

• Inflammatory markers show no mediating effect.