APPLICATION OF A NEW SERUM ASSAY FOR TYPE-I COLLAGEN CROSS-LINKED N-TELOPEPTIDES - ASSESSMENT OF DIURNAL CHANGES IN BONE TURNOVER WITH AND WITHOUT ALENDRONATE TREATMENT

Biochemical markers of bone turnover are finding increased application in the investigation and management of skeletal diseases such as oste oporosis. The present study assessed for the first time the diurnal va riation of serum type I collagen cross-linked N-telopeptides (NTx), a new serum-based marker of bone resorption, and the effect of antiresor ptive therapy with alendronate on this marker in elderly osteopenic wo men. The concentrations of serum NTx were monitored over 24 hours in a randomly selected subset of 35 women (placebo n = 13, 69 +/- 3 (SD) y ear; alendronate n = 25, 69 +/- 3 year), who had completed 12-15 month s of a larger (n = 120) randomized? double-blind, parallel group, plac ebo-controlled trial with alendronate 5 mg/day. Blood was obtained eve ry 4 hours for measurement of serum NTx using a new chemiluminescent-b ased immunoassay. There was a significant diurnal variation of serum N Tx (p = 0.001) in both the placebo and alendronate groups. Mean peak l evels occurred at similar to 0504 h with a mean nadir at similar to 13 20 hin the placebo group, with no significant difference on alendronat e. Serum NTx was similar to 25% lower in the alendronate group over th e entire 24-hour period. Mean (SE) daytime (0800-2000) and nighttime ( 2200-0800) serum NTx values were 6.40 +/- 0.30 versus 8.45 +/- 0.58 nm ol BCE/liter, and 7.42 +/- 0.23 versus 10.01 +/- 0.53 nmol BCE/liter f or alendronate versus placebo, respectively (P less than or equal to 0 .003 for both comparisons). Combining the data of both treatment group s, serum NTx was significantly (P < 0.05) correlated with serum osteoc alcin (r = 0.753) and urine NTx (r = 0.628) measurements previously ob tained over the entire 24-hour period. Serum NTx has a significant diu rnal variation and is responsive to antiresorptive therapy with alendr onate. Alendronate reduces the amplitude but maintains the pattern of the 24-hour serum NTx profile. These data suggest that serum NTx may b e a useful new marker of bone resorption.