Non-Hepatic Alkaline Phosphatase, hs-CRP and Progression of Vertebral Fracture in Patients with Rheumatoid Arthritis: A Population-Based Longitudinal Study

Jih-Chen Yeh, Chang-Chin Wu, Cheuk-Sing Choy, Shu-Wei Chang, Jian-Chiun Liou, Kuo-Shu Chen, Tao-Hsin Tung, Wei-Ning Lin, Chih-Yu Hsieh, Chun-Ta Ho, Ting-Ming Wang, Jia-Feng Chang

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BACKGROUND: Interactions and early warning effects of non-hepatic alkaline phosphatase (NHALP) and high-sensitivity C-reactive protein (hs-CRP) on the progression of vertebral fractures (VFs) in patients with rheumatoid arthritis (RA) remain unclear. We aim to explore whether serum concentrations of NHALP and hs-CRP could serve as a promising dual biomarker for prognostic assessment of VF progression.

METHODS: Unadjusted and adjusted hazard ratios (aHRs) of VF progression were calculated for different categories of serum NHALP and hs-CRP using the Cox regression model in RA patients. The modification effect between serum NHALP and hs-CRP on VF progression was determined using an interaction product term.

RESULTS: During 4489 person-years of follow-up, higher NHALP (>125 U/L) and hs-CRP (>3.0 mg/L) were robustly associated with incremental risks of VF progression in RA patients (aHR: 2.2 (95% confidence intervals (CIs): 1.2⁻3.9) and 2.0 (95% CI: 1.3⁻3.3) compared to the lowest HR category, respectively). The interaction between NHALP and hs-CRP on VF progression was statistically significant (p < 0.05). In the stratified analysis, patients with combined highest NHALP and hs-CRP had the greatest risk of VF progression (aHR: 4.9 (95% CI: 2.5⁻9.6)) compared to the lowest HR group (NHALP < 90 U/L and hs-CRP < 1 mg/L).

CONCLUSIONS: In light of underdiagnoses of VFs and misleading diagnosis by single test, NHALP and hs-CRP could serve as compensatory biomarkers to predict subclinical VF progression in RA patients.

Original languageEnglish
JournalJournal of Clinical Medicine
Issue number11
Publication statusPublished - Nov 13 2018


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