Numerous factors influence bone turnover, but there are even more sources of variability that need to be taken into account when measuring bone turnover with biochemical markers. To minimize preanalytical and analytical variability, the mode of sample collection, handling and storage needs to be standardized. Controllable factors such as diurnal and menstrual rhythms, presampling exercise and diet should be taken into account and eliminated whenever possible. Laboratories are encouraged to establish their own reference ranges and to use gender- and age-specific reference intervals. In order to reduce variability further, standardization of bone marker assays and the implementation of routine proficiency testing programmes are strongly recommended.

Even when all controllable influences are either eliminated or corrected for, a substantial degree of variability will still remain with most bone markers. Therefore, changes in marker measurements always need to be interpreted against

Figure 13.6 Effect of renal failure on serum and urine markers of bone turnover. Box and whisker plot of z-scores for various bone turnover markers measured in 25 patients with renal failure (creatinine clearance [cc] below 30 ml/ min; mean cc=23 ml/min). Boxes represent the median 50% of values, whiskers the 10-90% range of values. Circles are values in the lower and upper 5% of the distribution. Solid lines inside the box are medians and dashed lines are means. The dashed line through 0 represents the median of healthy premenopausal women (Seibel, unpublished data).

the background of the respective marker's total variability. A true change in marker levels can only be assumed when it exceeds the long-term coefficient of variability by at least 2-fold. As a rule, markers showing 'dramatic' changes in response to disease processes or therapeutic interventions usually show equally 'dramatic' degrees of nonspecific variability.


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