Usefulness of bone resorption markers in hemodialysis patients

Although bone biopsy is a golden standard in the diagnosis of renal osteodystrophy, it is invasive and repetitive evaluation of bone status by this method is practically impossible. Non-invasive evaluation by bone metabolic markers such as serum cross-linked N-telopeptide of type I collagen (NTX) might give us additional information which cannot be obtained only by measurements of parathyroid hormone (PTH). These days, bone resorption marker, serum tartrate-resistant acid phosphatase (TRAP5b) was reported to be correlated with histomorphometric parameters of bone resorption in a bone biopsy study enrolling hemodialysis (HD) patients. In the current study, we studied the correlation of sera NTX and TRAP5b with bone mineral density (BMD) of second metacarpal bone in 103 HD patients and serial changes of these markers just after parathyroidectomy (PTX). Sera NTX and TRAP5b showed a significant positive relationship (R=0.79 P<0.0001). Simple regression analyses showed that both markers were significantly associated with BMD Z-score, whereas 1-84 PTH showed no significant association at all. This result might be attributed to diverse difference among HD patients in skeletal sensitivity to endogenous PTH. In fact, the ratios of TRAP5b/PTH and NTX/PTH denoting PTH sensitivity were significantly higher in postmenopausal female than male patients. Female gender, hemodialysis vintage, and log(PTH) were found to be significant positive determinants of serum log(TRAP5b) by multiple linear regression analysis. Receiver operating curve analysis for young adult mean 70% revealed that sensitivity was more than 95% when the cut-off value was set at 56.5 nmol BCE/L and 340 mU/L, but the specificity was only 29.5% and 34.4% for NTX and TRAP5b, respectively. Multiple regression analysis revealed that both markers were independent determinants of Z-score in two models including respective marker. Serial changes of both markers after PTX in 2 HD patients were comparable with gradual decrease of these markers. However, the reduction was sooner and larger in serum NTX. This sooner reduction might be attributed to the difference in characteristics of these markers regarding the effect of single HD session. Whereas serum NTX decreased, TRAP5b increased significantly after single session. Taken together, both markers give us additional information that cannot be obtained just by using PTH, provided that we know the characteristics of these markers.