Bone alkaline phosphatase isoforms in hemodialysis patients with low versus non-low bone turnover: a diagnostic test study

Abstract

Background: Renal osteodystrophy encompasses the bone histologic abnormalities seen in patients with chronic kidney disease (CKD). The bone-specific alkaline phosphatase (bALP) isoform B1x is exclusively found in serum of some patients with CKD.

Study design: The aim of this cross-sectional diagnostic test study was to examine the relationship between serum bALP isoform activity and histomorphometric parameters of bone in patients with CKD receiving maintenance hemodialysis.

Settings & participants: Anterior iliac crest bone biopsy samples from 40 patients with CKD were selected on the basis of bone turnover for histomorphometric analysis. There were samples from 20 patients with low and 20 with non-low bone turnover.

Index test: In serum, bALP, bALP isoforms (B/I, B1x, B1, and B2), and parathyroid hormone (PTH) were measured.

Reference test: Low bone turnover was defined by mineral apposition rate < 0.36μm/d. Non-low bone turnover was defined by mineral apposition rate ≥ 0.36μm/d.

Other measurements: PTH.

Results: B1x was found in 21 patients (53%) who had lower median levels of bALP, 18.6 versus 46.9U/L; B/I, 0.10 versus 0.22 μkat/L; B1, 0.40 versus 0.88 μkat/L; B2, 1.21 versus 2.66 μkat/L; and PTH, 49 versus 287pg/mL, compared with patients without B1x (P<0.001). 13 patients (65%) with low bone turnover and 8 patients (40%) with non-low bone turnover (P<0.2) had detectable B1x. B1x correlated inversely with histomorphometric parameters of bone turnover. Receiver operating characteristic curves showed that B1x can be used for the diagnosis of low bone turnover (area under the curve [AUC], 0.83), whereas bALP (AUC, 0.89) and PTH (AUC, 0.85) are useful for the diagnosis of non-low bone turnover.

Limitations: Small number of study participants. Requirement of high-performance liquid chromatography methods for measurement of B1x.

Conclusions: B1x, PTH, and bALP have similar diagnostic accuracy in distinguishing low from non-low bone turnover. The presence of B1x is diagnostic of low bone turnover, whereas elevated bALP and PTH levels are useful for the diagnosis of non-low bone turnover.

Keywords: B/I, B1x, B1, B2; Bone-specific alkaline phosphatase (bALP); bALP isoforms; bone histology; diagnostic test study; end-stage renal disease (ESRD); hemodialysis; low bone turnover; mineral apposition rate; parathyroid hormone (PTH); renal osteodystrophy.

Figure 1

Study flow diagram.

Figure 2

ROC curves of (A) B1x for diagnosis of low bone turnover defined by mineral apposition rate < 0.36 µm/d and (B) bALP (—) and PTH (…) for diagnosis of non-low bone turnover defined by mineral apposition rate ≥ 0.36 µm/d.

Figure 2

ROC curves of (A) B1x for diagnosis of low bone turnover defined by mineral apposition rate < 0.36 µm/d and (B) bALP (—) and PTH (…) for diagnosis of non-low bone turnover defined by mineral apposition rate ≥ 0.36 µm/d.