title: Abnormal bone remodeling process is due to an imbalance in the receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin (OPG) axis in patients with solid tumors metastatic to the skeleton.
abstract: The role of receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin (OPG) system, and osteopontin (OPN) was studied in patients with solid tumors metastatic to the bone in relation to the type of malignancy and the neoplastic burden to the skeleton. Levels of soluble RANKL (sRANKL), OPG and OPN were assessed in 61 patients with breast, lung and prostate cancer with newly-diagnosed metastasis to the bone, in parallel with bone resorption [C-telopeptide of type-I collagen (CTX), tartrate-resistant acid phosphatase-5b (TRACP-5b)] and bone formation markers [bone-alkaline phosphatase (bALP), osteocalcin (OC), and C-terminal propeptide of collagen type-I (CICP)]. Patients had elevated serum levels of sRANKL, OPG, OPN, TRACP-5b, and bALP, and reduced OC levels compared to controls. OPG correlated with the extent of metastatic bone burden. Patients with breast and lung cancer shared increased levels of sRANKL, OPG, and OPN whereas prostate cancer patients had elevated values of OPG and bALP only. These results suggest that patients with solid tumors metastatic to the bone have severe disruption of the sRANKL/OPG axis. Breast and lung cancer seem to exert their osteolytic action through upregulation of the sRANKL/OPG system and OPN, whereas prostate cancer seems to provoke profound elevation of OPG levels only, thus leading to increased osteoblastic activity.
authors: Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece. gmountzios@med.uoa.gr
authors: Giannis
authors: G
authors: Mountzios
authors: Meletios-Athanassios
authors: MA
authors: Dimopoulos
authors: Aristotelis
authors: A
authors: Bamias
authors: George
authors: G
authors: Papadopoulos
authors: Efstathios
authors: E
authors: Kastritis
authors: Konstantinos
authors: K
authors: Syrigos
authors: George
authors: G
authors: Pavlakis
authors: Evangelos
authors: E
authors: Terpos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000378:metabolism; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000556:secondary*; D016723:Bone Remodeling; D001842:Bone and Bones / Q000473:pathology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D010006:Osteoblasts / Q000378:metabolism; D053495:Osteopontin / Q000032:analysis / Q000378:metabolism; D053244:Osteoprotegerin / Q000097:blood* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D053245:RANK Ligand / Q000097:blood* / Q000378:metabolism; D012863:Skeleton; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D053244:Osteoprotegerin; D053245:RANK Ligand; D053495:Osteopontin