Efficacy of simultaneous determination of bone alkaline phosphatase mass concentration in serum and urinary excretion of pyridinium cross-links for detection of bone metastases

In a fiTo examine the diagnostic validity of bone alkaline phosphatase (BAP) in serum (a marker of bone formation) and of urinary excretion of pyridinium cross-links (PYR) (a marker of bone resorption) for detection of bone metastases. Two heterogeneous immunoassays were employed for determination of BAP mass concentrations (Tandem®-R Ostase™) in serum and the urinary excretion of PYR (Collagen Crosslinks™) in a consecutive series of 89 tumor patients examined by bone scintigraphy (with 99mTc-methylene diphosphonate). The discrimination power (as determined by Z score analysis) and the accuracy (as assessed by the area under the receiver-operating characteristic curve) was higher fot BAP (0.84) than for PYR (0.76). Combination of both markers yielded a further increase of accuracy (0.89). There was a correlation (r = +0.422; p< 0.001) between the urinary excretion of pyridinium cross-links and bone alkaline phosphatase mass concentrations in the whole of 89 patients examined. In 14 (16%) of 89 patients bone alkaline phosphatase values were within the reference interval in spite of total alkaline phosphatase activity being increased; this indicates a higher diagnostic specificity of alkaline phosphatase (compared with total alkaline phosphatase) with respect to detection of bone metastases. Simultaneous assessment of bone formation by BAP and of bone resorption by PYR provides a suitable tool for detection of bone metastases. rst evaluation step we created a variety of pUC18 clones derived from mitochondrial control region amplifications with defined sequence differences and length. These clones were used as standard material for an optimization of the PCR-SSCP analysis. The optimized PCR-SSCP was then applied to large cohorts of patients with known, i.e., sequenced mtDNA point mutations and to healthy controls in order to evaluate its sensitivity.