Clinical Significance of Bone-Specific Alkaline Phosphatase as a Marker of Bone Turn-Over In Hemodialysis Patients: Impact of Metabolic Acidosis on Various Bone Markers

Park, Ki Ryung; Kang, Duk Hee; Lee, Eun Young; Choi, Kyu Bok; Yoon, Kyun Il

Abstract

Renal osteodystrophy is a leading cause of morbidity in patients with end stage renal disease(ESRD), including a diverse clinical spectrum and histologic lesions. Since the invasiveness and practical limitations of bone biopsy to diagnose the exact nature of bone disease in ESRD patients, many attempts have been made to investigate the biologic markers of bone disease. Bone-specific alkaline phosphatase(bAP) is localized in the plasma membrane of osteoblast to be involved in bone formation and skeletal mineralization. This study was undertaken to evaluate the value of bAP in the diagnosis of renal osteodystrophy and to examine the correlation between bAP (Immunoassay, Metra, U.S.A.) and other known markers of bone turn-over, total alkalilne phosphatase (tAP), intact parathyroid hormone(iPTH) and osteocalcin in 49 HD patients(M:F 29:20, mean age 51 years, mean HD duration 57 months). We also evaluated the impact of metabolic acidosis, which is known to stimulate the osteoclastic activity and bone resorption, on plasma levels of these bone markers. The median value of bAP in HD patients was 30.1ng/ml with a distribution of 8.8-140.1ng/ml (normal 12-23ng/ml). There was a significant positive correlation between the duration of HD and plasma levels of tAP, bAP, iPTH and osteocalcin. Significant positive correlaton was also observed between iPTH and other markers of bone turn- over-bAP, tAP and osteocalcin. bAP was correlated better with iPTH(r=0.8483, P<0.001) than tAP(r= 0.7588, P<0.01). In the patients group whose arterial blood bicarbonate below 20mEq/L(30 cases), plasma iPTH and bAP were significantly higher compared to the patients with arterial bicarbonate higher than 20mEq/L(19 cases). In conclusion, high bAP can be an useful marker of increased bone turn-over in HD patients. Increased concentrations of iPTH and bAP in patients with metabolic acidosis(arterial bicarbonate below 20 mEq/L) may reflect an increased bone resorption with resultant increase in osteoblast activity. However, a prospective study with alkali supplementation and bone biopsy will be necessary to define the exact role of metabolic acidosis in the development and progression of renal osteodystrophy.