RESEARCH THEME: BONE & JOINT
Orthopaedic Research
The Orthopaedic and Trauma Research programs are
mainly concerned with studies of prosthetic wear, spinal
pathology, osteoarthritis and trauma pathology. Fundamental
to their success is the ongoing collaboration between the
Department of Orthopaedic Surgery and Trauma, Royal Adelaide
Hospital with key research groups in the Hanson Institute,
Adelaide University and the Institute of Medical and Veterinary
Science. As a consequence, the Department enjoys a national
and international presence in clinical and basic science
orthopaedic and trauma research.
Clinical studies include a large international multi-centre
Phase II clinical trial examining the performance of the
manufactured human bone morphogenetic protein (rhBMP-2)
in the healing of tibial shaft fractures; the establishment
of an important Phase I clinical study to investigate the
role of bisphosphonates for the non-surgical treatment of
bone loss, and the development of a coordinating administration
for multi-centre joint replacement, spinal and trauma clinical
studies in Australia.
Another major activity is the animal model study investigating
the efficacy of a new treatment using bone morphogenic protein,
to stimulate new bone formation and bone graft incorporation
around hip replacements. The surrogate human body project,
involving the Department of Defence Science and Technology
Organisation and Anatomical Sciences, Adelaide University,
is progressing with the development of the thoracic cage
of the surrogate skeleton to examine traumatic impact of
defence weaponry on human bones.
The Orthopaedic Bone Cell Biology Laboratory continues
to study the basic biology of bone in health and disease
with particular focus in three areas; the cause of osteoarthritis;
the mechanisms of bone loss in rheumatoid arthritis, around
orthopaedic prostheses, and in cancer; and the search for
treatments for cancers in bone.
These studies involve the basic biology of cells responsible
for bone formation (osteoblasts) and bone removal (osteoclasts).
Much of this work is performed by growing cells artificially
in culture. Scientists have investigated how their culture
results match with actual events within human bone samples,
as well as comparing human bone structure with the expression
of particular genes. This work has attracted considerable
attention, which they believe will shed light on the underlying
basis of diseases such as osteoporosis and osteoarthritis.
The activity of cells destroying bone (osteoclasts) is
determined by a balance between the products of two genes,
one of which promotes bone resorption and the other which
dampens this activity. They have now shown that these molecules
are released under conditions previously not realised to
involve the skeleton such as inflammation and rheumatoid
arthritis. Further studies have found that these particular
genes are produced in association with bone resorption in
human bone and that micro-cracks in human bone might be
a stimulus for activating genes involved in stimulating
the formation of bone resorbing cells. This work is important
in understanding diseases such as osteoporosis and osteoarthritis
where these cellular processes are different.
Cancer studies have provided information that would allow
the use of lower levels conventional cancer-killing drugs
and so reduce the severity of the side-effects they cause
in patients. These experiments identified an unexpected
activity of a naturally occurring cell signalling molecule
found in bone. When this molecule is combined with a number
of conventional anti-cancer, chemotherapeutic drugs, it
killed osteosarcoma cancer cells at lower concentrations
than when it was not present.
In the next year the laboratory intends to test some of
their observations made in cell culture experiments by performing
experiments in animal models. In addition, the laboratory
has much to learn about the intracellular events that are
responsible for many of the effects of various agents on
bone and cancer cells. To understand how drugs and other
agents act, it is important because it can help target future
therapies to specific cell types.
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