title: Long-term variability of bone turnover markers in patients with non-metastatic breast cancer.
abstract: Variability of bone marker measurements is a major problem in their clinical application. Most studies on marker variability have been performed in healthy subjects and over relatively short intervals of time. We prospectively evaluated the long-term variability of bone markers in 102 postmenopausal women diagnosed with primary breast cancer. During follow up (8-48, median 30 mo.), no patient developed bone metastases or other skeletal disease. Patients were seen every 3 months and exactly timed blood/urine specimens were obtained. All analyses were performed after study end by the same technician, using a single batch of reagents per analyte. The coefficient of variation was calculated as CV (%) = square root(sigma(CVi2)/n) (CVi = SD/mean x 100; n = n of CVi). The least significant change (LSC) was then LSC (%) = Z x CV x square root(2). Z = 1.96 for a 95% confidence interval (LSC-95). In a subset of n = 10 patients with no potential interference during follow-up, lowest CVs were recorded for serum (s) calcium (5%), sTAP (12%) and sBAP (14%). The LSC-95 for these markers were 14%, 33% and 39%, respectively. Highest CVs were seen with urine (56%) and serum (42%) CTX (LSC-95: 155%, 117% resp.). We conclude that in breast cancer patients without bone metastases, long-term variability varied greatly between markers. For certain markers, the LSC seems considerably higher than previously reported.
authors.affiliation: Dept. of Endocrinology & Metabolism, Concord Hospital Medical Centre, University of Sydney, Australia. mjs@anzac.edu.au
authors.forename: M J
authors.initials: MJ
authors.lastname: Seibel
authors.forename: M
authors.initials: M
authors.lastname: Koeller
authors.forename: B
authors.initials: B
authors.lastname: Van der Velden
authors.forename: I
authors.initials: I
authors.lastname: Diel
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016723:Bone Remodeling; D001943:Breast Neoplasms / Q000503:physiopathology*; D002118:Calcium / Q000097:blood; D003094:Collagen / Q000097:blood / Q000652:urine; D024042:Collagen Type I; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D010455:Peptides / Q000097:blood / Q000652:urine; D017698:Postmenopause; D011446:Prospective Studies; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; D000469:Alkaline Phosphatase; D002118:Calcium