Collagen N-telopeptide excretion in men: the effects of age and intrasubject variability

Biochemical markers of bone resorption are useful for evaluating metabolic bone diseases. A three-center study was performed in 253 men, 21-86 yr of age, to determine the normal range of urinary N-telopeptide of type I collagen (NTX/creatinine) in a nonfasting, second void, morning specimen, to define the biological variability and to examine the relationship between NTX/creatinine and age. Men with disorders or taking medications known to alter bone turnover, or with a serum creatinine level greater than 2 mg/dL were excluded. Results are expressed as nanomoles of bone collagen equivalents (BCE) per mmol creatinine. In a subset of individuals over age 30 yr, additional second void morning urine specimens were obtained at 2, 3, and 4 days (short term study) and at 2, 3, and 4 months (long term study) after the first specimen. After collection, samples were shipped to one laboratory for analysis. Multiple samples from the same subject were analyzed in separate assays. It was found that urinary NTX/ creatinine was significantly higher in 45 men, aged 21-30 yr, than in 206 men, aged 31-86 yr (48 +/- 22 vs. 33 +/- 15 nmol/L BCE/mmol/L creatinine; P < 0.00001). Values did not otherwise change with age. The range of values in men aged 21-30 yr was 4-92 nmol/L BCE/mmol/L creatinine. The range for men over age 30 yr was 3- 63 nmol/L BCE/mmol/L creatinine, essentially the same as that previously reported for premenopausal women. The coefficient of variation was determined in each individual for the short term (n = 36) and long term studies (n = 35) and averaged 18% and 19%, respectively. There was no correlation between short term and long term coefficient of variations. In summary, urinary NTX/creatinine is higher in men aged 21-30 yr than in men over age 30 yr and may reflect continued skeletal maturation. Intrasubject variability of urinary NTX/creatinine in short term and long term studies has been defined for clinical purposes.