title: Markers of bone remodeling and skeletal morbidity in patients with solid tumors metastatic to the skeleton receiving the biphosphonate zoledronic acid.
abstract: The molecular triad, which includes the receptor activator of nuclear factor kappa-B ligand (RANKL), its receptor RANK, and the endogenous soluble RANKL decoy receptor osteoprotegerin (OPG), has emerged as an important determinant of bone metabolism. We aimed to evaluate the effect of treatment with the biphosphonate zoledronic acid (ZA) on biochemical markers of bone remodeling and to detect possible correlations of markerlevel changes with skeletal morbidity and clinical outcomes in patients with solid tumors and osseous metastases. The following serum markers were measured at the onset of skeletal metastases and after 6 months of treatment with ZA (4 mg intravenously monthly) in 70 patients with breast (n = 30), lung (n = 18), or prostate (n = 22) cancer: RANKL, OPG, C-terminal cross-linking telopeptide of type I collagen (CTX), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), bone-specific alkaline phosphatase (bALP), and osteopontin (OPN). Logistic regression models were applied to assess the correlation between marker-level changes and skeletal related events (SRE, primary endpoint), recurrence or progression, and death. Within a median follow-up of 32 months, 34 patients (48.6%) presented with at least 1 SRE and 48 patients (68.6%) relapsed. The RANKL/OPG ratio was upregulated in patients with breast and lung cancer, and it tended to decline after treatment with ZA, whereas prostate cancer patients presented with profound elevation of OPG only that persisted after treatment. CTX levels were significantly reduced after treatment in the whole study population (P = 0.003). None of the markers was able to predict skeletal morbidity or clinical outcomes independently of well-established prognostic clinical parameters.
authors.affiliation: Department of Medical Oncology, 251 General Airforce Hospital, University of Athens, Athens, Greece. gmountzios@med.uoa.gr <gmountzios@med.uoa.gr>
authors.forename: Giannis
authors.initials: G
authors.lastname: Mountzios
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Syrigos
authors.forename: Christos
authors.initials: C
authors.lastname: Papadimitriou
authors.forename: Giorgos
authors.initials: G
authors.lastname: Papadopoulos
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Bamias
authors.forename: Myron
authors.initials: M
authors.lastname: Mavrikakis
authors.forename: Meletios-Athanassios
authors.initials: MA
authors.lastname: Dimopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy*; D016723:Bone Remodeling / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D013125:Spinal Neoplasms / Q000556:secondary*; D000077211:Zoledronic Acid
chemical_list: D014408:Biomarkers, Tumor; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid