Bisphosphonates induce apoptosis of circulating endothelial cells in multiple myeloma patients and in subjects with bisphosphonate-induced osteonecrosis of the jaws.
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.
Allegra
Alessandro
A
Division of Hematology, University of Messina, Messina, Italy.
Alonci
Andrea
A
Penna
Giuseppa
G
Granata
Angela
A
Nastro Siniscalchi
Enrico
E
Oteri
Giacomo
G
Loddo
Saverio
S
Teti
Diana
D
Cicciù
Domenico
D
De Ponte
Francesco Saverio
FS
Musolino
Caterina
C
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
D050071:Bone Density Conservation Agents; D004164:Diphosphonates