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Circadian variation in serum CrossLaps concentration is reduced in fasting individuals.

To the Editor:

Accurate assessment of bone resorption may be of significant value for selecting women for antiresorptive therapy, monitoring of therapeutic response in treated individuals, and predicting fracture risk (1). This goal may be facilitated by measurement of biochemical markers of bone metabolism. The Serum CrossLaps[TM] One Step ELISA measures fragments derived from the C-terminal telopeptide of collagen type I. This assay has been shown to provide a sensitive and specific index of bone resorption (2,3).

An important issue for the use of biochemical markers is biological variability. This has been reported to be relatively high for specific markers of bone resorption. A recent letter by Wichers et al. (4) reports on the circadian variation in serum CrossLaps concentration in young males. Similar to what has been found for other specific markers of bone resorption, they report a pronounced circadian variation in serum CrossLaps concentration, with a nocturnal peak and a daytime nadir (5,6). The amplitude of the variation was reported to be 60-66% of the mean values observed over the 24-h observation period. The six study subjects were allowed to eat and drink throughout the experiment.

In this letter, I show that fasting can have a pronounced effect on the circadian variation of markers of bone resorption. Fig. 1 shows the circadian variation in serum CrossLaps concentration in 11 premenopausal women who were subjected to a randomized crossover study. In one part of the study, the women fasted overnight (2200-0800) before initiation of the study, but were then allowed to eat and drink without restriction during the 24-h study period. In the other part of the study, they fasted from 10 h before the study and then 24 h throughout the study. Serum samples were obtained at 3-h intervals throughout the study and measured in the Serum CrossLaps One Step ELISA. The results are shown as the average percentage of the individual mean ([+ or -] SE) for the two groups (Fig. 1). In fasting individuals, the average variation was 6 13.6%, whereas the variation under nonfasting conditions was [+ or -] 34%. The maximum changes from the 24-h mean were 20.3% and 44.8% for fasting and nonfasting women, respectively. Especially pronounced was the change in serum CrossLaps concentration seen in nonfasting women in the period from 0800 to 1100. Wichers et al. (4) also reported a similar pronounced decrease in this time interval for nonfasting men. However, the change in serum CrossLaps concentration in this time interval in fasting women was significantly lower.


From these results, we can conclude that the circadian variation of serum CrossLaps concentration is significantly lower in fasting than in nonfasting individuals. Thus, measurement of serum CrossLaps in morning fasting samples significantly reduces individual variability of the marker compared with measurement of serum samples from nonfasting individuals. Morning samples from individuals who have been fasting overnight are easily obtained in a clinical setting because this practice is used for several other common laboratory measures.

Wichers et al. (4) are right to conclude that control of sampling time is important in reducing individual variability in specific measures of bone resorption, but an equally or more important issue is to obtain samples from fasting individuals.


(1.) Kanis JA. Biochemical markers in osteoporosis. Scand J Clin Lab Investig 1997;57(Suppl 227):6-11.

(2.) Ravn P, Clemmensen B, Christiansen C. Biochemical markers can predict the response in bone mass during Alendronate treatment in elderly postmenopausal women. Bone 1999; 24:237-44.

(3.) Christgau S, Rosenquist C, Alexandersen P, Bjarnason NH, Ravn P, Fledelius C, et al. Clinical evaluation of the Serum CrossLapsTM One Step ELISA, a new assay measuring the serum concentration of bone derived degradation products of type I collagen C-telopeptides. Clin Chem 1998;44:2290-301.

(4.) Wichers M, Schmidt E, Bidlingmaier F, Klingmu muller D. Diurnal rhythm of CrossLaps in human serum. Clin Chem 1999;45:1858-60.

(5.) Schlemmer A, Hassager C. Acute fasting diminishes the circadian rhythm of biochemical markers of bone resorption. Eur J Endocrinol 1999;140:332-7.

(6.) Aoshima H, Kushida K, Takahashi M, Ohishi T, Hoshino H, Suzuki M, Inoue T. Circadian variation of urinary type I collagen crosslinked Ctelopeptide and free and peptide-bound forms of pyridinium crosslinks. Bone 1998;22:73-8.

Stephan Christgau

Osteometer BioTech A/S

Herlev Hovedgade 207 DK-2730 Herlev, Denmark

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Title Annotation:Letters
Author:Christgau, Stephan
Publication:Clinical Chemistry
Article Type:Letter to the editor
Date:Mar 1, 2000
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