GRAFT FOR SPINE FUSION SURGERY
There is a lot of interest
in the spine community to develop a bone graft substitute to use during
lumbar spinal fusion surgery procedures. This would eliminate the need
to harvest the patient’s own bone, thus potentially reducing the
risk and pain associated with the procedure and hopefully leading to a
more reliable result (e.g higher fusion rates).
Spinal fusion surgery entails
stopping the motion at a painful motion segment (the joint formed by two
vertebral bodies). The theory is that if the joint does not move, it will
not create pain. The fusion itself is achieved placing bone along or in
between the vertebral bodies. As the bone grows, it fuses the vertebrae
together and eliminates the motion at that segment of the spine.
CURRENT BONE GRAFT PROCEDURES FOR SPINE FUSION
The gold standard for bone
graft used for lumbal spine fusion has been bone harvested from the patient’s
pelvis, which is a surgical procedure performed at the time of the spine
There are two main potential
problems with harvesting bone from the patient’s pelvis:
Graft site morbidity
Taking the bone graft from the patient’s pelvis is a surgical procedure.
With proper surgical techniques, bone graft site morbidity can be decreased.
There is, however, always the potential for a complication. Some of these
potential complications include bleeding, infection, and chronic pain
at the donor site.
Failure to fuse (pseudoarthrosis or nonunion)
Even if the spine fusion operation is performed correctly, not every patient
will obtain a solid fusion. Spinal instrumentation has to some extent
reduced the risk of not getting a solid fusion, but there are some patient
who are still at high risk for a pseudoarthrosis (e.g.) patients who have
had multiple spine surgeries, who are obese, who smoke, or are having
a multilevel spine fusion.
The above two issues, graft
site morbidity and failure to fuse, are the two primary reasons there
has been a great deal of interest in creating a bone graft substitute
for use in a spine fusion procedure instead of using the patient’s
SOLID SPINE FUSION
To achieve a solid spine fusion,
three processes are necesaary:
Osteoconduction - this refers to the scaffolding that
is needed for new bone to grow on.
Osteogenicity - this refers to the transmittal of live
bone cells or osteoblasts.
Osteoinduction - this is the process whereby proteins
and growth factors induce the bone to grow.
(PATIENT’S OWN BONE)
Bone that is harvested from
the patient (autologous bone graft, or autograft bone) has two of these
properties because it has both the calcium scaffolding (osteoconduction)
and it is estimated that some 15% of the bone cells survive the transplantation
(osteogenicity). However, the third property – osteoinduction may
not be sufficiently available in the patient’s own bone. Although
small amounts of osteoinductive proteins are present in all bone matrix,
since autograft is mineralized bone, these osteoinductive proteins are
not exposed and may have very limited activity.
Donor bone, which is bone from
a cadaver and is referred to as allograft bone, has only the osteoconductive
property. It does not contain bone cells or proteins, and has only a calcium
scaffolding. Although donor bone seems to work well elsewhere in the spine
(e.g. neck) it is not sufficient for a spine fusion in the lumbar spine
(lower back). Allograft bone has been shown to not work well in a posterior
lateral fusion, which is a common type of spine fusion, when compared
with autologous bone graft (patient’s own bone). Sometimes allograft
bone is used anteriorly (in the front of the spine) as an interbody device
(bone dowel), but autologous bone harvested from the patient’s pelvis
is almost always used along with it. The interbody device provides the
structural support and the harvested bone graft from the patient’s
pelvis is what eventually fuses.
Similar to the patient’s
own bone, structural allograft bone comes fully mineralized so the osteoinductive
proteins are not exposed and readily active. Recent developments have
seen the advent of surfaced demineralize allograft that can combine the
structural integrity of bulk allograft with the osteoinductivity of demineralized
bone matrix (see explanation of demineralize bone matrix in the Bone graft
SUBSTITUTES FOR SPINE FUSION SURGERY
A third opinion, which is a
newer area of development in spine fusion surgery, is the field of bone
graft substitutes. There are several types of bone graft substitutes currently
available for use as an adjunct to, or as a substitute for, the above
two bone graft options.
TYPES OF BONE
GRAFT SUBSTITUTES FOR SPINE FUSION
There are several different
types of bone graft substitutes that are either currently available or
are in various stages of development for use in spine fusion surgery.
Demineralized Bone Matrix (DBM)
has been readily available for over ten years. This is a manufactured
product that includes demineralized pieces of cortical bone to expose
the osteoinductive proteins contained in the matrix. These proteins include
the family of bone morphogenetic proteins (BMP’s – see below)
known to be able to induce new bone formation de novo. These activated
demineralized bone particles are usually added to a substrate or carrier
(e.g. glycerol or a polymer). DBM is mostly an osteoinductive product,
but lacks enough induction to be used in its own in challenging healing
environments such as posterolateral spine fusion. It is almost always
used as a bone graft extender (not as a substitute) for posterolateral
spine fusion surgery and is generally intended to allow the use of less
Recently, a fiber-based (rather
than particle-based) DBM formulation has been shown to enhance the healing
success rate of spine fusions in the challenging rabbit and rhesus monkey
models (Grafton Matrix DBM, made by Osteotech). This is the first commercially
available DBM product that has been validated in a non-human primate spine
fusion model and the first shown to increase the fusion success rate above
that seen with autogenous bone graft. The increased activity is presumed
to be related to more optimal preservation of the activity of the osteoinductive
proteins as well as improved osteoconductivity provided by the fibers
of bone as compared to that with standard particles. Several laboratories
have shown this material to have superior activity in vivo in comparative
Several papers have been presented
at the North American Spine Society since 2000 that showed that some,
but not all, brands of commercially available DBM do enhance bone growth
in experimental tests. There is great variability between the efficacy
(osteoinductivity) of different brands of DBM and few have been properly
validated in stringent animal models. Because these materials are tissue
rather than devices, clinical trials are not required and there are very
limited human data available.
Bone Morphogenic Proteins (e.g BMP-2 or BMP-7) have been
shown to be excellent at growing bone and there are several products being
tested. Extensive animal testing has already been undertaken, and human
trials are finished and in process for these products.
BMP-2 delivered on an absorbable
collagen sponge (Infuse, made by Medtronic Sofamor Danek) has been used
inside titanium fusion cages and resulted in fusion in 11 out of 11 patients
in a pilot study and 99% of over 250 patients in a pivotal study. In July,
2002 the infuse brand of BMP received FDA approval for use in certain
types of spine fusion. A pilot study with BMP-2 delivered on a ceramic
carrier was recently published and reported a 100% successful posterolateral
fusion rate. BMP-7 (OP-1) has reported 50-70% successful posterolateral
lumbar fusion results in human studies to date. Studies with these and
other BMP’s are underway.
It is important to note that
use of BMP’s may add cost to an already very expensive operation.
Not only will researchers need to show that it is safe over the long term
and that it works, but they will need to show that it is cost effectie
before it will earn widespread support in the medical community.
Bone graft substitute combined with the patient’s
own bone marrow is another possible means to reduce bone graft site morbidity
and enhance fusion rates.
Bone marrow contains osteoprogenitor
cells (1/50,000-100,000 cells) and can be osteogenic, depending on how
the bone marrow is isolated.
Extensive testing has been
done in Europe on a product (Healos) that is a matrix made up of collagen
with hydroxyappetite spun onto it. Microscopically it closely resembles
bone and it works by absorbing harvested bone marrow before insertion.
Therefore, with marrow it has both osteoconductive and osteogenic properties,
yet it would eliminate the need for an open incision (to retrieve bone
from the patient’s hip) as the patient’s bone marrow can be
harvested with a needle. It also may be less expensive than BMP’s,
although it may not be as effective. Animal studies have yielded conflicting
results with respect to its success in posterolateral spine fusions.
Other strategies involving
the concentration of bone marrow aspirate are being investigated as well.
These strategies could increase the number of progenitor cells from marrow
by approximately 5-fold, however, the actual number of progenitors would
still be relatively small. This strategy has not been satisfactorily proven
in primates to date.
Development of bone graft substitutes
is currently one of the highest areas of interest in the spine community
– for patients considering spine fusion, for spine surgeons and
for companies developing the products. Judging by the amount of resources
being devoted to the task of developing a safe and effective bone graft
substitute, it is probably just a matter of time before a patient’s
own bone will no longer need to be harvested as part of a fusion procedure
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