title: Prognostic value of serum markers of bone metabolism in untreated multiple myeloma patients.
abstract: Bone involvement is a central feature of multiple myeloma (MM). We investigated whether serum markers of osteoblastic and osteoclastic activity correlate with the presence of bone disease and survival in 313 MM patients enrolled in a phase III trial (E9486). Five markers were measured, including osteocalcin (OC), carboxy-terminal propeptide of type I collagen (PICP), bone alkaline phosphatase (BAP), carboxy-terminal telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase (TRAP). We analysed the relationship between serum levels of these markers and the presence of bone manifestations, and survival. Serum levels of ICTP and BAP correlated significantly with bone pain, lesions and fractures. Serum level of ICTP was also higher in stage II-III compared with stage I disease. The serum level of ICTP was significantly associated with shortened survival in the univariate analysis. The median survival times were 4.1 and 3.5 years for low and high ICTP respectively (P = 0.02). There was a strong relationship between ICTP and beta-2-micrgolobulin (B2M). ICTP stands out as a significant marker of bone disease. Incorporation of these markers into clinical trials assessing the use of bisphosphonates in MM is needed to determine whether they might serve as indicators of effectiveness of these agents.
authors.affiliation: Department of Pathology and Laboratory Medicine, Rochester, MN 55905, USA.
authors.forename: R
authors.initials: R
authors.lastname: Fonseca
authors.forename: M C
authors.initials: MC
authors.lastname: Trendle
authors.forename: T
authors.initials: T
authors.lastname: Leong
authors.forename: R A
authors.initials: RA
authors.lastname: Kyle
authors.forename: M M
authors.initials: MM
authors.lastname: Oken
authors.forename: N E
authors.initials: NE
authors.lastname: Kay
authors.forename: B
authors.initials: B
authors.lastname: Van Ness
authors.forename: P R
authors.initials: PR
authors.lastname: Greipp
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D001859:Bone Neoplasms / Q000097:blood* / Q000150:complications / Q000401:mortality; D003094:Collagen / Q000097:blood*; D024042:Collagen Type I; D018572:Disease-Free Survival; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000150:complications / Q000401:mortality; D015999:Multivariate Analysis; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood*; D011347:Procollagen / Q000097:blood; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D024042:Collagen Type I; D006023:Glycoproteins; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C042813:procollagen type I carboxy terminal peptide; D015675:Osteocalcin; D003094:Collagen; C091137:purple acid phosphatase; D000135:Acid Phosphatase