0:04
Let's just turn and
discuss denosumab.
This is one of the newer
treatments for osteoporosis,
and its availability grew
out of new understanding
of the molecular control and
modulation of bone remodeling.
As you're aware, RANK
Ligand is a protein secreted
by osteoblasts and osteoclasts.
The action to RANK LIGAND is
necessary for the activation
and proliferation of osteoclasts.
Denosumab is a fully human
monoclonal antibody that binds
to and then activates RANK Ligand.
And as a result,
denosumab therapy inhibits
the differentiation proliferation
and activity of osteoclasts
and substantially
reduces bone resorption.
As with bisphosphonates because
of a decrease number in activity
of osteoclasts, the feedback
to osteoblast is reduced,
and there is a secondary
inhibition bone formation as well.
The pharmacokinetics of denosumab,
which is given subcutaneously,
is complex.
One dose of 60 milligrams
or greater reduces bone
turnover for at least six months.
In the studies that
have been performed,
denosumab therapy results in
a progressive increase in bone
mineral density over at least
the first eight years of therapy,
different and greater in
magnitude than we observe
with bisphosphonate therapy.
Because of the pharmacokinetics,
once therapy is discontinued,
there's a very rapid and complete
reversal of the effects on bone
remodeling within just
a few weeks of missing
the every six-month dose.
