title: Bisphosphonates induce apoptosis of circulating endothelial cells in multiple myeloma patients and in subjects with bisphosphonate-induced osteonecrosis of the jaws.
abstract: Bisphosphonates (BPs) are the current standard of care for bone lesions in patients with multiple myeloma (MM) but they are associated with a number of side effects such as osteonecrosis of the jaw. The exact mechanisms of osteonecrosis are not elucidated, and its physiopathology is based on several hypotheses such as a decrease in bone remodeling or an inhibitory effect on angiogenesis. The aim of our study was to investigate the mechanism involved in the pathogenesis of osteonecrosis. We examined the apoptosis of circulating endothelial progenitor cells in MM subjects before and after BP treatment and in osteonecrosis patients using a flow-cytometric analysis. Our data showed an increase in endothelial cell apoptosis in MM patients after BP administration and in osteonecrosis subjects. Our study seems in agreement with the hypothesis that BPs can inhibit angiogenesis interfering with endothelial cell proliferation and survival, leading to loss of blood vessels and avascular necrosis.
authors.affiliation: Division of Hematology, University of Messina, Messina, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Allegra
authors.forename: Andrea
authors.initials: A
authors.lastname: Alonci
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Penna
authors.forename: Angela
authors.initials: A
authors.lastname: Granata
authors.forename: Enrico
authors.initials: E
authors.lastname: Nastro Siniscalchi
authors.forename: Giacomo
authors.initials: G
authors.lastname: Oteri
authors.forename: Saverio
authors.initials: S
authors.lastname: Loddo
authors.forename: Diana
authors.initials: D
authors.lastname: Teti
authors.forename: Domenico
authors.initials: D
authors.lastname: Cicciù
authors.forename: Francesco Saverio
authors.initials: FS
authors.lastname: De Ponte
authors.forename: Caterina
authors.initials: C
authors.lastname: Musolino
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects; D002470:Cell Survival / Q000187:drug effects; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007571:Jaw Diseases / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010020:Osteonecrosis / Q000139:chemically induced* / Q000473:pathology
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates