Serum N-terminal telopeptide of type I collagen as a biomarker for predicting bone density loss in patients with Crohn disease

Abstract

Background: The serum N-terminal telopeptide of type I collagen (NTx) is significantly higher in patients with Crohn disease (CD) than in healthy individuals and patients with ulcerative colitis. This study aimed to investigate whether an elevated serum NTx level is a risk predictor of osteoporosis in patients with CD.

Methods: Based on whether the femoral Z-score decreased over a 2-year period, 41 CD patients were divided into the ΔZ-score <0 group (Z-score decreased) and the ΔZ-score ≥0 group (Z-score did not decrease). The risk predictors of a femoral Z-score decrease were examined. Furthermore, we investigated the correlations between the ΔZ-score (which represents the change in the Z-score over a 2-year period) and the mean levels of biomarkers, including the Crohn Disease Activity Index (CDAI), serum albumin, C-reactive protein, and bone metabolism markers (including NTx) measured initially (i.e., in our previous study) and 2 years later (present study). The relationships between anti-tumor necrosis factor α (anti-TNF-α) therapy and serum NTx levels were also examined.

Results: Although there was no correlation between the mean CDAI and the ΔZ-score, the mean serum NTx and albumin levels were significantly correlated with the ΔZ-score (P<0.01 and P = 0.02, respectively). Furthermore, the femoral Z-score tended to be lower in the anti-TNF-α administration group than in the non-administration group.

Conclusions: These observations indicated that an elevated serum NTx could be a useful marker for predicting a decrease in the femoral bone mineral density in CD patients. Anti-TNF-α therapy maintained an elevated serum NTx level, suggesting that treatment with anti-TNF-α may help control increased bone resorption in CD patients.

Fig 1. Receiver operating characteristic (ROC) curve of NTx for predicting the Z score decrease for 2 years.

ROC analysis indicates an optimal cut-off value of NTx predicting Z score decrease is 16.6 nmol BCE/L, and the area under the curve is 0.826 (95% confidence interval 0.694–0.958).

Fig 2. Correlation between the femoral neck ΔZ-score and the mean biomarker levels.

Scatter plots of the femoral neck ΔZ-score and the mean CDAI (a), mean NTx (b), and (c) mean Alb. CDAI, Crohn Disease Activity Index; NTx, serum N-terminal telopeptide of type I collagen; Alb, albumin.

Fig 3. Serum NTx levels in the anti-TNF-α administration and non-administration groups.

The serum NTx levels at the first measurement and 2 years later are shown for each group. NTx, N-terminal telopeptide of type I collagen; TNF-α, tumor necrosis factor α.

Fig 4. Change in the Z- and ΔZ-scores of the femoral neck.

(a) Femoral neck Z-scores of the anti-TNF-α administration and non-administration groups at the first measurement and 2 years later. (b) Femoral neck ΔZ-scores of the anti-TNF-α administration and non-administration groups. TNF-α, tumor necrosis factor α.