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

Abstract

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.

Uremic Vascular Calcification Is Correlated With Oxidative Elastic Lamina Injury, Contractile Smooth Muscle Cell Loss, Osteogenesis, and Apoptosis: The Human Pathobiological Evidence

“…After a careful review of medical records, hepatobiliary diseases were excluded in our patient groups. Thus, raised circulating ALP levels in our study were determined to be non-hepatic origins, such as bone events or CKD-mineral bone diseases (18). Nonhepatic ALP is a byproduct of osteoblast activity, and increased hydrolysis of mineralization inhibitor pyrophosphate by ALP enhances UVC in CKD (19).…”

Scavenging Intracellular ROS Attenuates p-Cresyl Sulfate-Triggered Osteogenesis through MAPK Signaling Pathway and NF-κB Activation in Human Arterial Smooth Muscle Cells

“…Patients with hepatobiliary diseases were excluded in our study after careful chart review. Thus the origins of elevated ALP concentrations were determined to be non-hepatic, such as CKD-mineral bone diseases or skeletal events [26]. Non-hepatic ALP is one of the most important osteoblast marker proteins for bone mineralization, hydrolysis of mineralization inhibitor pyrophosphate, and UVC associated mortality in CKD patients [27].…”

A Joint Evaluation of Neurohormone Vasopressin-Neurophysin II-Copeptin and Aortic Arch Calcification on Mortality Risks in Hemodialysis Patients

“…Given that both VP and AAC were intricately involved in EOVC related fatal events, we assumed that the mortality risk would be augmented among patients with higher levels of VP and AAC. In this study, the modification effect between AAC and VP on all-cause and CV mortality was examined using an interaction product term according to previous methods of moderation analysis (1,19,26,33). As expected, the effects of VP on allcause and CV mortality risks were modified by AAC in the multivariable model.…”