Associations of serum skeletal alkaline phosphatase with elevated C-reactive protein and mortality

Abstract

Background and objectives Higher serum total alkaline phosphatase (AP) levels are associated with increasedserum C-reactive protein (CRP) levels and mortality in the general and CKD populations. It is unclear to what extent these associations are related to bone disease. Design, setting, participants, & measurements In a nationally representative sample of 10,707 adult participants from the 1999-2004 National Health and Nutrition Examination Survey, serum nonskeletal AP levels were estimated from the measured serum skeletal and total AP levels. The associations of serum skeletal AP and nonskeletal AP levels with elevated serum CRP concentrations (>3 mg/L) and mortality were examined in multivariable models. Results Skeletal AP was not associated with elevated CRP (for each doubling in non-CKD: odds ratio [OR], 1.00; 95% confidence interval [95% CI], 0.90-1.11; in CKD: OR, 1.19; 95% CI, 0.83-1.70) or mortality (for each doubling in non-CKD: hazard ratio [HR], 1.10; 95% CI, 0.94-1.29; in CKD: HR, 0.98; 95% CI, 0.75-1.28). In contrast, non-skeletal AP was associated with elevated CRP (for each doubling in non-CKD: OR, 4.51; 95% CI, 3.80-5.35; in CKD: OR, 5.98; 95% CI, 3.40-10.51). Nonskeletal AP was associated with mortality in non-CKD (for each doubling: HR, 1.96; 95% CI, 1.37-2.80) but not in CKD (for each doubling: HR, 0.92; 95% CI, 0.51-1.67) (interaction P=0.03). Conclusions Bone disease is unlikely to account for the known associations of serum total AP with increased inflammation and mortality. © 2013 by the American Society of Nephrology.