Comparison of serum bone resorption markers in the diagnosis of skeletal metastasis.
BACKGROUND
There are several bone resorption markers which are generated by different mechanisms. The serum level of 3 different bone resorption markers in cancer patients with or without skeletal metastasis was compared to see whether the markers exhibit clinically significant differences useful for metastatic screening.


METHODS
Serum bone metabolic markers were measured in 75 cancer patients with and 201 cancer patients without skeletal metastasis. The 3 bone resorption markers, N-terminal cross-linked telopeptide of type I collagen (NTx), pyridinoline cross-linked carboxy-terminal telopeptides of type I collagen (ICTP) and tartrate-resistant acid phosphatase type 5b (TRAP 5b), and two bone formation markers, procollagen type I C-terminal peptide (PICP) and procollagen type I N-terminal peptide (PINP), were measured in the single sample. Each marker serum level was compared with the menopausal and the osseeous metastatic status assessed using Soloway's method for each patient.


RESULTS
Bone resorption marker serum levels, except for ICTP, were about 16% larger in postmenopausal patients than in premenopausal patients. All 3 bone resorption marker serum levels were 3-4 times greater in patients with extensive skeletal metastasis (extent of disease III; EOD = III) than in patients with no osseous metastasis. Although ROC analysis indicated each bone resorption marker had a similar sensitivity and specificity regarding the ability to detect osseous metastasis, some differences were detectable. The T-score of TRAP 5b was elevated, but not significantly so, in patients with a small bone metastatic burden (EOD = I). In contrast, although the T-score of NTx was not elevated in patients with a small metastatic burden (EOD = I), it was significantly elevated in patients with extensive osseous metastasis (EOD = III).


CONCLUSIONS
Three bone resorption markers with different generation mechanisms showed a difference in menopause and osseous metastasis status. The level of ICTP was not elevated in postmenopausal patients, but the levels of NTx and TRAP 5b. In osseous metastasis, even though not statistically significant, TRAP 5b increased in patients with a small bone metastatic burden and NTx increased in patients with extensive bone metastatic burden.
Koizumi
Mitsuru
M
Department of Nuclear Medicine, Cancer Institute Hospital, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan. mitsuru@jfcr.or.jp
Takahashi
Shunji
S
Ogata
Etsuro
E
D000135:Acid Phosphatase / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D001859:Bone Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000556:secondary*; D001862:Bone Resorption / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000473:pathology; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007527:Isoenzymes / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood / Q000473:pathology; D008297:Male; D010455:Peptides / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology; D012372:ROC Curve
D014408:Biomarkers, Tumor; D024042:Collagen Type I; D006023:Glycoproteins; D007527:Isoenzymes; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; C091137:purple acid phosphatase; D000135:Acid Phosphatase