TY - JOUR
TI - Myeloma bone-disease and proteasome inhibition therapies
AU - Terpos, Evangelos
AU - Sezer, Orhan
AU - Croucher, Peter
AU - Dimopoulos,
AU - Meletios-Athanassios
JO - Blood advances
PY - 2007
VL - 110
TODO - 4
SP - 1098-1104
PB - AMER SOC HEMATOLOGY
SN - null
TODO - 10.1182/blood-2007-03-067710
TODO - null
TODO - Bone disease is one of the most debilitating manifestations of multiple
myeloma. A complex interdependence exists between myeloma bone disease
and tumor growth, creating a vicious circle of extensive bone
destruction and myeloma progression. Proteasome inhibitors have recently
been shown to promote bone formation in vitro and in vivo. Preclinical
studies have demonstrated that proteasome inhibitors, including
bortezomib, which is the first-in-class such agent, stimulate osteoblast
differentiation while inhibiting osteoclast formation and bone
resorption. Clinical studies are confirming these observations.
Bortezomib counteracts the abnormal balance of osteoclast regulators
(receptor activator of nuclear factor-kappa B ligand and
osteoprotegerin), leading to osteoclast inhibition and decreased bone
destruction, as measured by a reduction in markers of bone resorption.
In addition, bortezomib stimulates osteoblast function, possibly through
the reduction of dickkopf-1, leading to increased bone formation, as
indicated by the elevation in bone-specific alkaline phosphatase and
osteocalcin. The effect of bortezomib on bone disease is thought to be
direct and not only a consequence of the agent’s antimyelorna
properties, making it an attractive agent for further investigation, as
it may combine potent antimyeloma activity with beneficial effects on
bone. However, the clinical implication of these effects requires
prospective studies with specific clinical end points.
ER -