Cross-linked N-telopeptide of type I collagen (NTx) in urine as a predictor of periprosthetic osteolysis.

Periprosthetic osteolysis is often nonsymptomatic and hard to visualize by conventional radiography. Cross-linked N-telopeptide of type I collagen (NTx), a marker of osteoclast mediated bone resorption, has been suggested to evaluate local particulate-induced osteolysis in patients operated on with a total hip prosthesis. Urine specimens were sampled after hip joint replacement in 160 patients. NTx was analyzed by a commercially available ELISA kit. Osteolysis was identified in the acetabulum and confirmed at operation. Using analysis of covariance to correct for differences in age, gender, and time after operation, NTx (mean SD) was 36+/-12 BCE/nM creatinine in patients with osteolysis (n=33) and 27+/-13 BCE/nM creatinine in patients without osteolysis (n=127) (p=0.003). Eighteen hips of 38 (47%), demonstrating an annual wear of more than 0.2 mm and an NTx value above 29 BCE/nM creatinine, had been revised due to osteolysis. The osteolysis prevalence in this group was increased 10 times (CI 4-23, p<0.05). Indeed, NTx release and annual wear were both associated with increased prevalence of osteolysis, however, independently of each other. NTx seems a feasible marker of periprosthetic osteolysis. A preoperative baseline NTx level is likely needed for its use as a predictor of periprosthetic osteolysis in individual cases.     

Early changes in urinary cross-linked N-terminal telopeptides of type I collagen level correlate with 1-year response of lumbar bone mineral density to alendronate in postmenopausal Japanese women with osteoporosis

The purpose of this study was to determine whether early changes in the urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX) during alendronate treatment would be correlated with the 1-year response of lumbar bone mineral density (BMD) in postmenopausal Japanese women with osteoporosis. One hundred five postmenopausal women with osteoporosis, aged 54–88 years, were treated with alendronate (5mg daily) for 12 months. The urinary NTX levels were measured by enzyme-linked immunosorbent assay at the baseline and at 3, 6, and 12 months, and lumbar (L1–L4) BMD was measured by dual-energy X-ray absorptiometry using the Hologic QDR 1500W equipment at the baseline and at 12 months. The mean percent reduction in urinary NTX level at 3, 6, and 12 months was 36.8%, 49.5%, and 49.0%, respectively, the extent of reduction at 6 and 12 months being greater than that at 3 months, and the mean percent increase of the lumbar BMD at 12 months was 8.2%. Single regression analysis showed a significant correlation between the percent reductions in the urinary NTX level at 3, 6, and 12 months of treatment and the percent increase of the lumbar BMD at 12 months (r = 0.200, P < 0.05; r = 0.341, P < 0.001; and r = 0.338, P < 0.001, respectively). Thirty percent of the patients were labeled as poor responders at 3 months, with the reduction in the urinary NTX level being less than the minimum significant change (MSC); 61% of these patients showed a greater reduction in the urinary NTX level, exceeding the MSC, at 6 months. These results suggest that the changes in the urinary NTX levels at 3 and 6 months after the start of alendronate treatment at the dose of 5mg daily may be correlated with the 1-year response of the lumbar BMD in postmenopausal Japanese women with osteoporosis. In other words, the greater the reduction of the urinary NTX level at 3 and 6 months after the start of alendronate treatment, the greater can be the expected increase of the lumbar BMD after 12 months of treatment. In this study, 70% of the patients were good responders, who showed a reduction of the urinary NTX level exceeding the MSC at 3 months. Among the remaining 30% poor responders, about 60% showed satisfactory reduction of the urinary NTX level, exceeding the MSC, at 6 months after the start of treatment with alendronate.