P1403
PLASMA OSTEOPONTIN LEVELS DIRECTLY CORRELATE WITH INTACT PARATHYROID HORMONE AND ALKALINE PHOSPHATE LEVELS IN END STAGE RENAL DISEASE

Bone turnover disorders and reduction in bone mineral density are commonly observed in end stage renal disease (ESRD) patients. Osteopontin (OPN) is a glycol-phosphoprotein that stimulates osteoclast adhesion to bone. OPN may play a significant role in the pathways involved in bone turnover disorders. The objective of this study was: (1) to identify plasma levels of OPN in ESRD and normal populations, and (2) to elucidate if relationships exist between OPN and iPTH, and OPN and alkaline phosphatase.

Plasma levels of OPN were measured via commercially available enzyme linked immunosorbent assays (ELISAs) in ESRD patients (n=92). A chart review was conducted on these patients to identify levels of intact parathyroid hormone (iPTH) and alkaline phosphatase at time of plasma draw. Additionally, levels of total calcium, albumin, calcium corrected for albumin, phosphorus, ferritin, white blood cell count (WBC), and platelet count (PLT CT) were identified at time of plasma draw via the chart review. OPN levels were also measured in normal control patient plasma (n = 49) purchased from George King Bio-Medical, Inc., Overland Park, KS.

The ESRD cohort showed a statistically significant elevation of OPN plasma levels (p < 0.0001, Mann-Whitney t-test) compared to the normal group. Spearman correlation tests revealed a significant positive correlation of OPN with iPTH (p < 0.0001; r = 0.5606, 95% confidence interval = 0.3968 to 0.6898) and OPN with alkaline phosphatase (p < 0.0001; r = 0.4381, 95% confidence interval = 0.2494 to 0.5948) in the ESRD cohort. No statistically significant correlations were identified between OPN and total calcium, calcium corrected for albumin, albumin, phosphorus, ferritin, WBC, and PLT CT (p > 0.05).

OPN levels are significantly elevated in ESRD patients. Furthermore, OPN levels were also found to be positively correlated with the bone turnover biomarkers iPTH and alkaline phosphatase. These studies suggest that hyperparathyroidism secondary to ESRD increases circulating iPTH, stimulating osteoblast and osteoclast activation and differentiation that increases alkaline phosphatase and OPN production, ultimately resulting in increased bone turnover.