A new approach for evaluating bone turnover in chronic kidney disease

The validity of serum parathyroid hormone (PTH) as a surrogate marker of bone turnover in chronic kidney disease (CKD) is limited by several factors such as relative resistance of bone to PTH, hyperphosphatemia, diabetes, gender, age, race and vitamin D analog action on the PTH-bone axis. Urinary collagen N-terminal telopeptide X (NTx), a bone collagen degradation product, expressed as bone collagen equivalents (BCE) per mM of creatinine (NTx/Cr ratio), is routinely used to estimate bone turnover in osteoporosis. The purpose of this study is to evaluate NTx as a marker of bone turnover in CKD.

We studied the relationship between bone-specific alkaline phosphatase (BSAP), PTH and urine NTx/Cr in 37 CKD out-patients.

In a multivariate model, PTH had a positive correlation with BSAP (r=0.44, P<0.19) and U-NTx/Cr (r=0.55, P<0.30), after adjusting for age, gender, estimated glomerular filtration rate (GFR), serum phosphorus, corrected calcium, and race. However, the strongest correlation was found between the two direct markers of bone resorption and formation (U-NTx vs. BSAP; r=0.80; P<0.0001), suggesting a tight coupling of bone resorption and formation in CKD. The effect of gender on U-NTx/Cr was studied in a multivariate model after adjusting for age, race, GFR, serum calcium, phosphorus and PTH. Females had a higher U-NTx/Cr than males.

Our findings indicate that urinary NTx, a promising marker of bone resorption in CKD patients, exhibits a strong positive correlation with other markers used to assess renal osteodystrophy i.e. PTH and BSAP. Unlike PTH and BSAP, urine NTx also measures bone loss secondary to osteoporosis.