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In
Vivo, Synchrotron Radiation Tomography in Osteoporosis Research
J.H. Kinney
<
br>
Lawrence Livermore National Laboratory and U.C.
San Francisco
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Osteoporosis
is a condition of low bone mass often associated with fracture. However,
bone mass, or bone mineral density (BMD), is not perfectly correlated
with fracture; there
is significant overlap of normal and osteoporotic
populations when fracture frequency is compared. To explain this overlap,
investigators have proposed risk factors in addition to bone mass,
such as deterioration of trabecular bone architecture.
Trabecular bone is a highly porous structure consisting of a latticework
of interconnecting rods and plates. It is a significant fraction of
the total bone mas
s in the vertebral bodies and the femoral neck,
anatomic sites normally associated with osteoporotic fracture. Relating
trabecular architecture to fracture risk is difficult. Trabecular
bone is a dynamic system; its architecture can adaptively compensate
for local deficiencies in strength through remodeling or micromodeling.
Our group has developed a three-dimensional, in vivo x-ray
microscope that allows us to image trabecular bone in small animals.
With this tool, we have been able to follow the evolution of trabecular
bone architecture in the same animals for several months after removal
of the ovaries to simulate menopause. Two significant findings have
come from these studies: 1) there is a significant decrease in the
connectivity of the trabecular lattice that parallels the loss of
bone mass, and
2) even if bone mass is regained with anabolic treatments
(like intermittent parathyroid hormone injections), the connectivity
is not restored. Subsequent studies with finite-element analysis of
the images suggest that in cases of severe bone loss, strength cannot
be recovered unless the connectivity of the trabecular lattice is
increased.
In light of these findings, we have recently explored the use o
f a
growth factor (basic fibroblast growth factor, or bFGF) to regenerate
new trabecular bone with the goal of reestablishing trabecular connectivity.
We have established that bFGF can generate new bone-like members in
the marrow cavity, but it is questioned whether the new bone reconnects
mechanically with the original lattice. In this presentation, we will
present our most recent results where we demonstrate that bFGF rest
ores
lost trabecular connectivity.
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