Clinical significance of bone alkaline phosphatase isoforms, including the novel B1x isoform, in mild to moderate chronic kidney disease

Abstract

Mineral bone disorder (MBD) is a common complication of chronic kidney disease (CKD) even during the early stages. Bone alkaline phosphatase (BALP) is a marker of bone formation and plays a pivotal role in the mineralization process. Three BALP isoforms (B/I, B1 and B2) have been identified in healthy individuals and a fourth isoform (B1x) has been discovered in serum from dialysis patients. We investigated these BALP isoforms, type I procollagen intact amino-terminal propeptide (PINP), carboxy-terminal telopeptide of type I collagen (CTX) and tartrate-resistant acid phosphatase isoform 5b (TRACP5b), as well as bone mineral density (BMD) in predialysis CKD patients. PINP, CTX, TRACP5b and BALP isoforms were analysed in serum from 46 patients within CKD stages 3-5. BMD was determined by dual-energy x-ray absorptiometry. PINP, TRACP5b and the BALP isoforms, B/I, B1 and B2, were independent predictors of total hip BMD in all patients. Furthermore, B/I predicted osteopaenia in the hip and in the distal 1/3 of the radius in CKD stage 3. The B1x isoform was detected in nine patients (20%), who had lower GFR, higher phosphate and calcium x phosphate product. We found an association of BALP isoforms and other markers of bone turnover with total hip BMD, which predominantly comprises trabecular bone. The association of the new BALP isoform B1x with risk factors for vascular calcification leads us to hypothesize a possible role for B1x in this process. The significance of the BALP isoforms in CKD remains to be further explored in experimental and clinical settings in conjunction with bone histomorphometry.