Recent Advances in Medical Applications of Synchrotron Radiation
Stanford Synchrotron Radiation Laboratory
March 4-5, 2002
Program Director: Edward Rubenstein
Keith Hodgson
James Rubenstein
Katsuhito Yamasaki
Helene Elleaume
Giuliana Tromba
Wolf-Rainer Dix
Kazuki Hyodo
Barton Lane
William Thomlinson
Hiroshi Sugiyama
Joseph Roberson
Masami Ando
John Kinney
Avraham Dilmanian
Dean Chapman
Zhong Zhong
Brenda Laster
Roman Tatchyn
Paul Csonka
In Vivo, Synchrotron Radiation Tomography in Osteoporosis Research

J.H. Kinney
< br> Lawrence Livermore National Laboratory and U.C. San Francisco
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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