Laboratory reproducibility of biochemical markers of bone turnover in clinical practice

Abstract

SummaryTo determine the laboratory reproducibility of urine N-telopeptide and serum bone-specific alkaline phosphatase measurements, we sent identical specimens to six US commercial labs over an 8-month period. Longitudinal and within-run laboratory reproducibility varied substantially. Efforts to improve the reproducibility of these tests are needed.IntroductionWe assessed the laboratory reproducibility of urine N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP).MethodsSerum and urine were collected from five postmenopausal women, pooled, divided into identical aliquots, and frozen. To evaluate longitudinal reproducibility, identical specimens were sent to six US commercial labs on five dates over an 8-month period. To evaluate within-run reproducibility, on the fifth date, each lab was sent five identical specimens. Labs were unaware of the investigation.ResultsLongitudinal coefficients of variation (CVs) ranged from 5.4% to 37.6% for NTX and from 3.1% to 23.6% for BAP. Within-run CVs ranged from 1.5% to 17.2% for NTX. Compared to the Osteomark NTX assay, the Vitros ECi NTX assay had significantly higher longitudinal reproducibility (mean CV 7.2% vs. 30.3%, p < 0.0005) and within-run reproducibility (mean CV 3.5% vs. 12.7%, p < 0.0005).ConclusionsReproducibility of urine NTX and serum BAP varies substantially across US labs.

Bone remodeling markers and bone metastases: From cancer research to clinical implications

“…11,17 To overcome preanalytical variability, laboratories must establish their own reference ranges using gender-and age-specific reference values, 11 and address intralaboratory reproducibility both in manual and automated assays. 18 The International Osteoporosis Foundation (IOF) and International Federation of Clinical Chemistry (IFCC), IOF/IFF working group, have published recommendations to minimize variability in the determination of bone remodeling markers. 19,20 One bone resorption marker, serum CTX-I, and one bone formation marker, serum P1NP, are considered as reference markers and measured by standardized assays in observational and intervention studies.…”

“…22 Over the past decade, most of the immunoassays that were used have been automated, contributing to the decrease of technical variability. 18 However, there are specific aspects of each remodeling biomarker that should be taken into account to control variability in their quantification.…”

Rapidly assessing changes in bone mineral balance using natural stable calcium isotopes

“…Mathematically combining these biochemical markers into a single quantitative measure of net BMB has not been and may not be possible, because neither marker can be quantitatively related to the rate of the process that it measures, let alone to the other marker (23,24). The application and interpretation of biochemical markers are also confounded by high interlaboratory analytical variability (25). However, interlaboratory variation of δ 44/42 Ca is within the analytical uncertainty for any single laboratory (9,26), which permits direct comparison between isotopic measurements made by different laboratories.…”

Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia

“…Changes in bone markers in response to treatment occur earlier and are of a greater magnitude than changes in bone density. A significant change in BMD can rarely be detected in an individual in response to oral anti-resorptive therapy in less than [18][19][20][21][22][23][24] months. Compliance with treatment is a concern in clinical practice and monitoring patients on treatment using biochemical markers can provide useful additional information for the management of patient care [14] .…”

“…Considerations for their use in clinical practice include cost effectiveness and also the variability of bone markers [16,17] . Studies have reported poor reproducibility of bone markers between laboratories [18,19] . The standardization of bone marker measurements is currently being addressed with the introduction of international reference standards [10] .…”