Another limitation of the present study is the testing of a single pooled sample for each marker, rather than the testing of multiple pooled samples representing high, normal, and low marker values. However, it is likely that the reproducibility of measurements at the extremes of or outside the normal range would show even greater variability. As each lab determines its own reference ranges, reference ranges

varied, but this should not affect measurement reproducibility. In addition, the assay used or the reference range cited by each lab may have changed after the completion of this study. Clinical laboratories evaluate the quality of their results through proficiency testing, which is required by the Clinical MK5108 laboratory Akt inhibitor Improvement Amendments TPCA-1 price and performed by organizations including the College of

American Pathologists, but survey results are not easily available to practicing clinicians. These and other evaluations of marker assays, such as one conducted as a part of a Centers for Disease Control study to develop a reference system to standardize the measurements of bone resorption markers pyridinium crosslinks pyridinoline and deoxypyridinoline [11], invite labs to participate and announce the tested specimens. While the results provide valuable information, the concern exists that reproducibility may be at its best during an announced test. The present study is important in that the serum and urine specimens submitted to the six high-volume US clinical labs investigated were processed as routine clinical specimens ordered by clinicians would be processed: the labs were unaware of the investigation, fictional identifiers were used, and the specimens were sent by the authors’ institutional clinical laboratory, so the specimens were indistinguishable from routine clinical specimens. This element of the study’s design was considered extremely

important, even though it prevented the direct observation eltoprazine of potential factors that might have explained some of the variability in lab reproducibility, such as the handling of specimens by different labs. In the past, some published studies comparing laboratory performance have published data without naming the laboratories [12, 13], but reaction in the literature has included the belief that the laboratories should be identified [14]; the present study provides laboratories’ names in order that the results and discussion generated be as useful as possible to clinicians. The identification of laboratories by name is similar to the identification of commercial assays by name when such assays are compared, and this is not uncommon in the literature [15–17]. Inconsistent reproducibility is a barrier to the use of biochemical markers of bone turnover in clinical practice, particularly if clinicians do not consistently use the same assay and laboratory.