Está en la página 1de 12

The PDF of the article you requested follows this cover page.

This is an enhanced PDF from The Journal of Bone and Joint Surgery
84:454-464, 2002. J Bone Joint Surg Am.
Christopher G. Finkemeier

Bone-Grafting and Bone-Graft Substitutes
This information is current as of March 30, 2006
Subject Collections
(96 articles) Bone Grafts
(101 articles) Multiple Body Sites/Systemic
(81 articles) Relevant to All Subspecialties
(349 articles) BASIC SCIENCE

Articles on similar topics can be found in the following collections
Reprints and Permissions
Permissions] link.
and click on the [Reprints and jbjs.org article, or locate the article citation on
to use material from this order reprints or request permission Click here to
Publisher Information
www.jbjs.org
20 Pickering Street, Needham, MA 02492-3157
The Journal of Bone and Joint Surgery
on March 30, 2006 www.ejbjs.org Downloaded from
COPYRIGHT 2002 BY THE JOURNAL OF BONE AND JOINT SURGERY, INCORPORATED
,
Current Concepts Review
Bone-Grafting and
Bone-Graft Substitutes
BY CHRISTOPHER G. FINKEMEIER, MD
Investigation performed at University of California Davis Medical Center, Sacramento, California
The treatment of delayed unions, malunions, and nonunions requires restoration of alignment, stable fixation,
and in many cases adjunctive measures such as bone-grafting or use of bone-graft substitutes.
Bone-graft materials usually have one or more components: an osteoconductive matrix, which supports the in-
growth of new bone; osteoinductive proteins, which support mitogenesis of undifferentiated cells; and osteo-
genic cells (osteoblasts or osteoblast precursors), which are capable of forming bone in the proper environment.
Autologous bone graft, usually harvested from the iliac crest, is an excellent graft material, but its availability
may be limited and the procedure to harvest the material is associated with complications.
Bone-graft substitutes can either replace autologous bone graft or expand an existing amount of autologous
bone graft.
Various forms of bone-graft substitutes are available and include allograft bone preparations such as demineral-
ized bone matrix and calcium-based materials.
The treatment of posttraumatic skeletal conditions such as de-
layed unions, nonunions, malunions, and other problems of
bone loss is challenging. In most cases, restoration of align-
ment and stable fixation of the bone is all that is necessary to
achieve a successful reconstruction. However, in many cases,
adjunctive measures such as bone-grafting or bone transport
are required to stimulate bone-healing and fill bone defects.
When faced with a problem requiring bone replace-
ment, the orthopaedic surgeon currently has several options:
autologous or allogeneic cancellous or cortical bone, deminer-
alized bone matrix, calcium phosphate-based bone-graft sub-
stitute, or autologous bone marrow. In the future, the options
will include recombinant bone morphogenetic proteins or
growth factors. The biology of each of these grafts varies and
may provide one or several essential components: (1) an os-
teoconductive matrix, which is a scaffold or trellis that sup-
ports the ingrowth of new bone; (2) osteoinductive proteins,
which stimulate and support mitogenesis of undifferentiated
perivascular cells to form osteoprogenitor cells; and (3) osteo-
genic cells (osteoblasts or osteoblast precursors), which are ca-
pable of forming bone if placed into the proper environment.
The surgeons choice of the proper graft must be based on
what is required from the graft (structural or bone-forming
function, or both), the availability of the graft, the recipient
bed, and the cost. The surgeon must also remember that stable
fixation is necessary for the use of any of these grafts
1
. No bone
graft or bone-graft substitute permits the surgeon to use less
than optimum orthopaedic techniques or to deviate from
proper surgical principles.
Conventional bone-grafting with autologous cortical
and cancellous bone harvested from the iliac crest is the stan-
dard against which all other bone-graft substitutes are judged,
but it has disadvantages. The supply of autologous bone graft
is limited, and many patients with difficult problems requiring
skeletal reconstruction may have undergone several previous
harvests of bone grafts and thus have little or no additional
useful iliac crest bone. In addition, the harvesting of autolo-
gous bone is associated with a rate of major complications of
8.6% and a rate of minor complications of 20.6%
2
. Another
problem is that enough autologous graft may not be available,
especially if there is massive segmental bone loss. For these
reasons, it is important to have various options available to
augment, expand, or substitute for autologous bone graft.
Autologous Bone Grafts
Autologous bone grafts have osteogenic, osteoconductive, and
osteoinductive properties. Available autologous bone grafts
include cancellous, vascularized cortical, nonvascularized cor-
tical, and autologous bone marrow grafts (Table I). Bone for-
mation from autologous grafts is believed to occur in two
phases
3,4
. During the first phase, which lasts approximately four
weeks, the main contribution to bone formation is from the
on March 30, 2006 www.ejbjs.org Downloaded from
,,
THE JOURNAL OF BONE & JOI NT SURGERY J BJ S. ORG
VOLUME 84-A NUMBER 3 MARCH 2002
BONE-GRAFTI NG AND
BONE-GRAFT SUBSTI TUTES
cells of the graft. During the second phase, cells from the host
begin to contribute to the process. The endosteal lining cells
and marrow stroma produce more than half of the new bone,
whereas osteocytes make a small (10%) contribution. Free he-
matopoietic cells of the marrow make a minimal contribution
5
.
Autologous cancellous bone is easily revascularized and
is rapidly incorporated into the recipient site. Cancellous graft
is a good space filler, but it does not provide substantial struc-
tural support. Because only the osteoblasts and endosteal lin-
ing cells on the surface of the graft survive the transplant, a
cancellous graft acts mainly as an osteoconductive substrate,
which effectively supports the ingrowth of new blood vessels
and the infiltration of new osteoblasts and osteoblast pre-
cursors
5-8
. Osteoinductive factors released from the graft dur-
ing the resorptive process as well as cytokines released during
the inflammatory phase may also contribute to healing of the
graft, although this is only a prevailing theory based on cir-
cumstantial evidence; it has not yet been substantiated by sci-
entific documentation
3,9,10
. Although cancellous graft does not
provide immediate structural support, it incorporates quickly
and ultimately achieves strength equivalent to that of a corti-
cal graft after six to twelve months
11
.
Autologous cancellous bone is commonly harvested
from the iliac crest, which can provide a large supply of bone
(especially the posterior iliac crest). Other sources are Gerdys
tubercle, the distal part of the radius, and the distal part of the
tibia. Autologous cancellous bone graft is an excellent choice
for nonunions with <5 to 6 cm of bone loss and that do not re-
quire structural integrity from the graft. It can also be used to
fill bone cysts or bone voids after reduction of depressed ar-
ticular surfaces such as in a tibial plateau fracture. However,
bone-graft substitutes may be preferable in these cases to avoid
donor site morbidity. Stable internal or external fixation is also
required, to provide the optimum environment for graft con-
solidation and successful fracture-healing.
Sources of autologous cortical grafts include the fibula,
ribs, and iliac crest. These grafts can be transplanted with or
without their vascular pedicle. Autologous cortical grafts have
little or no osteoinductive properties and are mostly osteocon-
ductive, but the surviving osteoblasts do provide some osteo-
genic properties as well
12,13
. Autologous cortical grafts provide
excellent structural support at the recipient site as well. Al-
though nonvascularized cortical grafts provide immediate
structural support, they become weaker than vascularized cor-
tical grafts during the initial six weeks after transplantation as
a result of resorption and revascularization
12,14
. However, by six
to twelve months there is little difference in strength between
vascularized and nonvascularized cortical grafts
12
. Vascular-
ized cortical grafts heal rapidly at the host-graft interface, and
their remodeling is similar to that of normal bone. Unlike
nonvascularized grafts, these grafts do not undergo resorption
and revascularization and, therefore, they provide superior
strength during the first six weeks
12
. Despite their initial
strength, cortical grafts still must be supported by internal or
external fixation to protect them from fracture while they hy-
pertrophy in response to Wolff s law
15
and mechanical load-
ing. Autologous cortical bone grafts are good choices for
segmental defects of bone of >5 to 6 cm, which require imme-
diate structural support. For defects of >12 cm, vascularized
grafts are superior to nonvascularized grafts as indicated by
failure rates of 25% and 50%, respectively
11
. The harvest of
large cortical grafts has been associated with some problems.
Tang et al. reported that, of thirty-nine patients who had a free
fibular graft harvested for treatment of avascular necrosis of
the femoral head, 42% had a subjective sense of instability and
37% had a subjective sense of weakness in the lower ex-
tremity
16
. Only mild weakness of great toe extension and flex-
ion could be measured in 43% and 29% of these patients,
respectively. Only 2% of the patients required a reoperation
for a problem at the donor site. Bone transport may be a bet-
ter option for defects of >6 cm
17,18
.
The advantages of autologous cancellous or cortical
bone grafts are their excellent success rate, low risk of trans-
mitting disease, and histocompatibility. However, as noted
above, there is a limited quantity of autologous bone graft and
there is the potential for donor site morbidity.
Bone Marrow
Another source of autologous material is the osteoblastic stem
cells found in bone marrow. Injections of autologous bone
TABLE I Properties of Types of Autologous Bone Grafts
Property Cancellous
Nonvascularized
Cortical
Vascularized
Cortical
Osteoconduction ++++
57
+
7,14
+
13
Osteoinduction ++* +/
7,13
+/
13
Osteoprogenitor cells +++
6,7

13
++
13
Immediate strength +++
58
+++
12
Strength at 6 mo ++
59
++
58
, +++
12
+++
12
Strength at 1 yr +++
59
+++
58
+++
12
*Although cancellous bone is widely believed to be osteoinductive, there is no evidence to critically demonstrate that inductive proteins and
cytokines are active in autologous cancellous bone graft.
on March 30, 2006 www.ejbjs.org Downloaded from
,o
THE JOURNAL OF BONE & JOI NT SURGERY J BJ S. ORG
VOLUME 84-A NUMBER 3 MARCH 2002
BONE-GRAFTI NG AND
BONE-GRAFT SUBSTI TUTES
marrow provide a graft that is osteogenic and potentially os-
teoinductive through cytokines and growth factors secreted
by the transplanted cells. Bone marrow can be aspirated from
the posterior iliac wing in volumes of 100 to 150 mL and can
be injected into a fracture or nonunion site to stimulate heal-
ing. When it is to be used in small bones such as the scaphoid,
the bone marrow aspirate can be centrifuged
19
to concentrate
the marrow cells and to maximize osteogenic stromal colony-
forming efficiency while decreasing the volume injected.
Muschler et al. showed that a 2-mL aspirate from a human
anterior iliac crest has a mean of 2400 alkaline phosphatase-
positive colony-forming units
20
. The larger the volume of the
aspirate, the greater the total number of alkaline phosphatase-
positive colony-forming units, but they are more diluted. An
increase in the volume of the aspirate from 1 to 4 mL de-
creases the concentration of alkaline phosphatase-positive
colony-forming units by 50%. Thus, the maximum number
of alkaline phosphatase-positive colony-forming units can be
delivered to the recipient site in four 1-mL aliquots as op-
posed to one 4-mL aliquot
20
.
This technique has potential problems because of the
tendency for the injected material to wash away from the frac-
ture site. Many authors have studied the effect of composite
grafts formed from a combination of bone-graft substitutes
and autologous bone marrow
21-25
. Demineralized bone matrix
is an excellent carrier because of its osteoconductive and os-
teoinductive properties. Connolly et al. used autologous bone
marrow mixed with 10 mg of demineralized bone matrix,
which forms a sand-like material, to fill bone defects
19,26
. This
composite graft can be injected percutaneously as well. Injec-
tion of autologous bone marrow, with or without a carrier, has
been used to treat nonunion and delayed union of several
bones (i.e., the carpal bones, tibia, femur, humerus, etc.). The
Type-IIIB open tibial fracture may be the ideal fracture for
this technique because of its high frequency of healing prob-
lems and the possible benefits of not having to expose the
fracture site to deliver the graft. Connolly reported that eigh-
teen (90%) of twenty delayed unions of the tibia united after
utilization of this technique
19
. He recommended waiting six to
twelve weeks after the acute fracture to allow the initial in-
flammatory reaction and osteoclastic resorption to subside
before injecting the autologous bone marrow
19
. Injection of
autologous bone marrow does not promote healing more rap-
idly or to a greater extent than do traditional bone-grafting
techniques
27-29
, but it has been shown to be as successful in one
small series
19
. Injection of autologous bone marrow offers sev-
eral advantages: (1) the technique is relatively simple and can
be done as an outpatient procedure and should, therefore, be
cost-effective
19,25
; (2) it is associated with fewer complications
at the donor and recipient sites than is harvesting of autograft
from the iliac crest
19,25
, although I am not aware of any direct
comparison studies upon which to base a final conclusion;
and (3) because the approach is less invasive, clinicians may be
encouraged to perform early treatment of delayed unions, ul-
timately expediting healing and decreasing the complications
of prolonged immobilization
30
.
Techniques for Harvesting Autologous
Cortical and Cancellous Bone Graft
Bone can be harvested from either the anterior or the poste-
rior iliac crest. Harvesting from the anterior iliac crest is usu-
ally more convenient because the patient is typically in a
supine position for most operations involving the extremities.
However, only a limited amount of bone can be obtained from
the anterior iliac crest, and this site should not be used when
>20 to 30 cc of graft is required. The posterior iliac crest, on
the other hand, has an abundant supply of both cortical and
cancellous bone and is an ideal location from which to harvest
large amounts of bone-graft material. The general technique
for harvesting bone from the ilium is similar regardless of
whether the bone is taken anteriorly or posteriorly. When
bone is harvested from the anterior iliac crest, I recommend
that the most anterior extent be at least 2 to 3 cm posterior
to the anterior superior iliac spine to avoid predisposing it to
an avulsion fracture. It is important to take advantage of the
relatively large amount of cancellous bone under the iliac tu-
bercle. When bone is taken from the posterior iliac crest, I rec-
ommend that the most posterior extent be at least 4 cm from
the posterior superior iliac spine to decrease the chance of vio-
lating the sacroiliac joint.
For illustrative purposes, I will describe my technique
for harvesting corticocancellous bone graft from the posterior
iliac wing (Fig. 1). The patient is placed in the prone position,
over bolsters, and all osseous prominences are well padded.
The buttock and flank ipsilateral to the operative site is pre-
pared and draped. A vertical incision is made, centered over
the proposed harvest area. Transverse incisions that parallel
the posterior iliac crest should not be used routinely, as they
may injure the cluneal nerves. The length of the incision is de-
termined by the amount of bone-graft material that is needed.
The deep fascia overlying the posterior iliac crest is incised
over the crest down to the bone. With use of a sharp Cobb ele-
vator and either a knife or an electrocautery, the fascia is then
elevated off the iliac wing, exposing either the outer table or
the inner table, depending on the surgeons preference. A lap
sponge placed over the sharp edge of a Cobb elevator can be
used to assist in clearing the periosteum. I typically expose the
outer table for harvesting. I then use a 0.5-in (12.7-mm) sharp
straight osteotome to cut a line into the iliac crest, starting 4
cm anterior to the posterior superior iliac spine and extending
as far anteriorly as needed. From this corticotomy, I then use a
straight 0.5-in osteotome to cut vertical lines toward the sciatic
notch (Fig. 1, A). It is imperative to be careful not to violate
the sciatic notch to avoid injury to the neurovascular pedicle,
which lies adjacent to the iliac wing in the sciatic notch. Strips
of graft of various widths can then be cut with the straight os-
teotome through the extent of the proposed harvest area.
Using a gouge of the same diameter as the cortical strip, I re-
move corticocancellous strips with abundant cancellous bone
attached to a thin layer of cortical bone from the iliac wing
(Fig. 1, B). These strips are placed into a sterile basin and cov-
ered with a damp sponge or towel. The remaining portion of
the cancellous bone within the iliac wing is then removed,
on March 30, 2006 www.ejbjs.org Downloaded from
,,
THE JOURNAL OF BONE & JOI NT SURGERY J BJ S. ORG
VOLUME 84-A NUMBER 3 MARCH 2002
BONE-GRAFTI NG AND
BONE-GRAFT SUBSTI TUTES
with use of a combination of gouges or large curets (Fig. 1, C).
Abundant cancellous bone is also available underneath the
iliac crest itself. More cancellous graft can be removed by un-
dermining in each direction from the harvest site.
Hemostasis can be obtained by packing a combination
of Gelfoam (Upjohn, Kalamazoo, Michigan) and thrombin
into the iliac wing, or bone wax can be applied to the raw os-
seous surfaces to stop the bleeding. Packing with lap sponges
also helps to control the bleeding. I recommend placing a me-
dium-sized suction drain deep to the fascia and then closing
the fascia with an absorbable heavy suture. The wound can be
closed according to the surgeons preference.
Other potential areas for harvesting bone include meta-
physeal regions of the skeleton, such as the distal part of the
radius, Gerdys tubercle, the tibial plafond, and the greater
trochanter. The harvesting technique is similar for all of these
areas, and I recommend a technique similar to that used to
perform a bone biopsy. A small drill bit should be used to
create perforations in an elliptical pattern. These perforations
are then connected with a small osteotome or a small curet to
remove the cortical roof. Beneath this roof there is a supply of
cancellous bone in various quantities, depending on the ana-
tomic region of the body from which the graft is being har-
vested. Once the graft is harvested, the small cortical roof can
be replaced, or it can be used as part of the bone graft. Hemo-
stasis can be obtained by packing with a sponge or with some
thrombin-impregnated Gelfoam. I usually do not use suc-
tion drainage in these locations. A compression dressing
works well to obtain hemostasis. Harvesting of any of the var-
ious vascularized pedicle flaps, such as the fibula or the iliac
crest, requires specialized techniques and is beyond the scope
of this review.
Allografts
Allogeneic bone, with variable biologic properties, is available
in many preparations: demineralized bone matrix, morselized
and cancellous chips, corticocancellous and cortical grafts,
and osteochondral and whole-bone segments.
Demineralized Bone Matrix
Demineralized bone matrix acts as an osteoconductive, and
possibly as an osteoinductive, material. It does not offer struc-
tural support, but it is well suited for filling bone defects and
cavities. Demineralized bone matrix revascularizes quickly. It
also is a suitable carrier for autologous bone marrow as dis-
cussed previously. Demineralized bone matrix is prepared by
a standardized process, as originally described by Urist et
al.
31,32
and modified by Reddi and Huggins
33
, in which alloge-
neic bone is crushed or pulverized to a consistent particle size
(74 to 420 m) followed by demineralization in 0.5N HCL
mEq/g for three hours. The residual acid is eliminated by
rinsing in sterile water, ethanol, and ethyl ether. Current
methods of processing demineralized bone matrix follow the
same basic steps, but refinements of the technique, many of
which have been patented, have been developed by several
companies and tissue banks. Process variables may include
demineralization time, acid application, temperature, appli-
cation of defatting agents, and use of either aseptic processing
methods or irradiation or ethylene oxide sterilization of the
final product. The companies and tissue banks market these
variations in processing with the claim that they provide
unique advantages and superior performance over other
products, although little comparative scientific data are avail-
able to support many of the claims.
The biologic activity of demineralized bone matrix is
Fig. 1
A: Posterior view of the pelvis. Strips of cortico-
cancellous bone as well as cancellous bone can
be harvested, with the most posterior extent of
the harvest being no closer than 4 cm from the
posterior superior iliac spine. B: Corticocancellous
strips consist of cancellous bone attached to a
thin layer of cortical bone. C: Cancellous bone
can be removed from between the inner and outer
tables of the ilium and is best stored in a
container where it can be kept moist.
on March 30, 2006 www.ejbjs.org Downloaded from
,8
THE JOURNAL OF BONE & JOI NT SURGERY J BJ S. ORG
VOLUME 84-A NUMBER 3 MARCH 2002
BONE-GRAFTI NG AND
BONE-GRAFT SUBSTI TUTES
presumably attributable to proteins and various growth fac-
tors present in the extracellular matrix and made available to
the host environment by the demineralization process. The
osteoinductive capacity of demineralized bone matrix can be
affected by storage, processing, and sterilization methods and
can vary from donor to donor. For example, sterilization by
ethylene oxide under certain conditions and 2.5 Mrad of
gamma irradiation substantially reduce osteoinductivity
34,35
.
Because the osteoinductive capacity differs from donor to do-
nor and because of safety reasons, the American Association
of Tissue Banks and the United States Food and Drug Admin-
istration require each batch of demineralized bone matrix to
be obtained from a single human donor
36
. Demineralized
bone matrix is available as a freeze-dried powder, as crushed
granules or chips, and as a gel or paste (Table II).
Demineralized bone matrix is an excellent grafting ma-
terial with which to induce bone formation within contained,
stable skeletal defects such as bone cysts and cavities
26,37,38
. Oth-
ers have reported that application of demineralized bone ma-
trix to long-bone nonunions and acute bone defects from
fractures results in successful healing similar to that following
autologous bone-grafting
26,39-41
. Demineralized bone matrix
can also be used to enhance healing of arthrodeses in the spine
and elsewhere
26,32
. The most successful grafts may be compos-
ites of demineralized bone matrix and autologous bone
marrow
19,26
when used with stable fixation. A dilute mixture of
demineralized bone matrix and autologous bone marrow can
be injected with a syringe, and this method has been used suc-
cessfully in many challenging situations
19,26
. Demineralized
bone matrix can also augment and expand autologous cancel-
lous bone graft when the supply of autogenous bone is limited
or the defect is very large.
I recommend demineralized bone matrix for filling sta-
ble, well-contained bone defects and cysts and as a bone-graft
expander when the defect is large. Although to my knowledge
no prospective, randomized controlled studies have been done
to prove the efficacy of demineralized bone matrix for the
treatment of nonunions, there may be some nonunion situa-
tions in which the use of demineralized bone matrix could be
considered. First, it can be used to augment autologous can-
cellous or corticocancellous grafts. Demineralized bone ma-
trix may also be an alternative for a patient who has no
autologous bone available for use as a graft or for a patient
who does not wish to undergo an extensive open procedure or
for whom the open procedure carries a very high risk. In this
case, a percutaneous procedure utilizing demineralized bone
matrix and autologous bone marrow could be considered. I
recommend using demineralized bone matrix as a composite
graft with autologous bone marrow to provide an immediate
supply of osteoprogenitor cells in combination with a matrix
that is both conductive and inductive
22,24
. However, while some
studies have shown successful outcomes with composite
grafts
19,26,42
, experience with these grafts is limited and their ef-
fectiveness is currently unproven.
Demineralized bone matrix has several potential disad-
vantages. Because it is an allogeneic material, there is the po-
tential to transmit human immunodeficiency virus (HIV).
However, the decalcification process appears to inactivate and
eliminate HIV
43
, so even if infected tissue got through the ex-
tensive donor screening process, the risk of transmission is
very low. According to one manufacturer, there have been no
reported cases of infectious disease transmission in 1.5 mil-
lion procedures with the use of one particular preparation of
demineralized bone matrix
44
. Similarly, one large tissue bank
that processes demineralized bone matrix reported in its liter-
ature that no infectious disease transmission had occurred
from more than 20,000 donors
45
. Another potential limitation
of demineralized bone matrix is that different batches may
have different potencies because of the wide variety of donors
used to supply the graft. Finally, although many authors have
reported healing similar to that following autologous cancel-
lous bone-grafting, I am not aware of any prospective, ran-
domized studies that would allow a true comparison of the
two graft types.
Morselized and Cancellous Allografts
Morselized and cancellous allografts are osteoconductive and
provide some mechanical support, mainly in compression.
They are most often preserved by freeze-drying (lyophiliza-
tion) and vacuum-packing, and they undergo stages of incor-
poration similar to those of autologous cancellous bone. I
recommend using morselized allograft for packing bone de-
fects such as bone cysts after curettage or in periarticular
metaphyseal locations to support elevated articular surfaces
TABLE II Demineralized Human Bone Matrix Preparations Cleared for Marketing in the United States or Europe
Product Company Type
Grafton DBM Osteotech Demineralized bone matrix; available in gel, flex, and putty forms
DynaGraft GenSci Regeneration Sciences Demineralized bone matrix
OrthoBlast GenSci Regeneration Sciences Demineralized bone matrix and allograft cancellous bone
Osteofil Sofamor Danek Demineralized bone matrix (24%) with gelatin carrier (17%) and water
Opteform Exactech Compacted corticocancellous bone chips mixed with the same material as Osteofil
DBX Synthes Demineralized bone matrix; available in putty or paste
on March 30, 2006 www.ejbjs.org Downloaded from
,,
THE JOURNAL OF BONE & JOI NT SURGERY J BJ S. ORG
VOLUME 84-A NUMBER 3 MARCH 2002
BONE-GRAFTI NG AND
BONE-GRAFT SUBSTI TUTES
Fig. 2-A
Fig. 2-A Preoperative anteroposterior radiograph of a depressed intra-articular tibial plateau fracture. The depressed articular surface is indicated
by the arrow. Fig. 2-B Postoperative anteroposterior radiograph made after reduction of the articular surface and coralline hydroxyapatite grafting of
the metaphyseal defect left behind after elevation of the articular surface, as indicated by the arrow.
Fig. 2-B
after articular depression such as occurs with tibial plateau or
tibial pilon fractures. Morselized allograft is also useful to aug-
ment autogenous cancellous bone and to fill larger defects
when the supply of autologous bone is limited. Allograft bone
is associated with a very small risk of infectious disease trans-
mission, but its use will eliminate the need to harvest iliac
crest bone and its associated morbidity.
Osteochondral and Cortical Allografts
Osteochondral and cortical allografts are harvested from vari-
ous regions of the skeleton, such as the pelvis, ribs, femur,
tibia, and fibula, for reconstruction after major bone or joint
loss. The grafts are available as whole-bone or joint segments
(i.e., as the whole or part of the tibia, humerus, femur, talus,
acetabulum, ilium, or hemipelvis) for limb salvage procedures
or as cortical struts to buttress existing bone, to stabilize and
reconstitute cortical bone after periprosthetic fractures, and
to fill bone defects. These grafts are osteoconductive and pro-
vide immediate structural support. They are preserved by ei-
ther deep-freezing or freeze-drying. Deep-frozen allografts
retain their material properties and can be implanted imme-
diately after thawing, whereas freeze-dried allografts can be
friable and weak in torsion and bending, even after rehydra-
tion prior to implantation. Again, transmission of infectious
disease is a risk when osteochondral and cortical allografts are
used. However, of the three million tissue transplants per-
formed since identification of the HIV virus, only two cases of
HIV transmission have occurred and both involved trans-
plantation of unprocessed fresh-frozen allografts
36
. I recom-
mend the use of cortical allografts to fill bone voids and for
reconstructive procedures requiring immediate structural
support in patients who wish to avoid harvest of an autolo-
gous fibular graft.
Fresh allografts that require no preservation are avail-
able, but they incite an intense immune reaction, making
them less attractive than autografts. These fresh allografts have
limited applications and are currently being used mainly for
joint resurfacing.
Ceramics and Ceramic Composites
Calcium phosphate ceramics may be used as osteoconductive
matrices in orthopaedic surgical settings (Table III). Many of
on March 30, 2006 www.ejbjs.org Downloaded from
oo
THE JOURNAL OF BONE & JOI NT SURGERY J BJ S. ORG
VOLUME 84-A NUMBER 3 MARCH 2002
BONE-GRAFTI NG AND
BONE-GRAFT SUBSTI TUTES
the current calcium phosphate biomaterials can be classified as
polycrystalline ceramics. The material structure of ceramics is
derived from individual crystals of a highly oxidized substance
that have been fused together at the crystal grain boundaries
by a high-temperature process called sintering
46
. Ceramics are
brittle and have poor tensile strength, making their primary
clinical application one of filling contained bone defects or re-
storing areas of bone loss resulting from a fracture such as an
articular fracture with joint depression. Calcium phosphate
biomaterials should be placed in intact bone or rigidly stabi-
lized bone in order to protect the ceramic from shear stresses,
and they should be tightly packed into the adjacent host bone
to maximize ingrowth
47
. Calcium phosphate ceramics are
available as porous or nonporous blocks of various sizes or as
porous granules. Calcium phosphate ceramics do not elicit a
foreign-body reaction and are well tolerated by host tissues.
Tricalcium phosphate is a random porous ceramic that
undergoes partial conversion to hydroxyapatite once it is im-
planted into the body
11
. Tricalcium phosphate is more porous
and is resorbed faster than hydroxyapatite, making it mechan-
ically weaker in compression
46
. After conversion, the hy-
droxyapatite is resorbed slowly and, therefore, large segments
of hydroxyapatite remain in place for years. Because trical-
cium phosphate has an unpredictable biodegradation profile,
it has not been popular as a bone-graft substitute
48
. However,
Bucholz et al. showed that tricalcium phosphate is effective for
filling bone defects resulting from trauma, benign tumors,
and cysts
47
.
Coralline hydroxyapatite is processed by a hydrothermal
exchange method that converts the coral calcium phosphate to
crystalline hydroxyapatite with pore diameters between 200
and 500 m and in a structure very similar to that of human
trabecular bone. Bucholz et al. reported that the clinical per-
formances of autologous cancellous bone graft and coralline
hydroxyapatite are equivalent when the substances are used to
fill bone voids resulting from articular surface depression in
tibial plateau fractures
49
. Other studies have demonstrated suc-
cessful healing of cortical defects greater than one-third of the
diaphyseal circumference of long-bone fractures, although the
results are less predictable than those following treatment of
metaphyseal fractures
47
. To avoid donor site morbidity, I occa-
sionally use coralline hydroxyapatite granules or blocks of vari-
ous size, depending on the size of the defect, to fill metaphyseal
defects after reduction of depressed articular segments (Figs.
2-A and 2-B). A contraindication to the use of this material is a
joint surface defect that would allow the grafting material to
migrate into the joint. In these cases, I prefer to use autologous
or allograft cancellous bone, which is more adhesive to itself
and to the surrounding metaphyseal bone.
Another ceramic bone-graft substitute currently in clin-
ical use is a calcium-collagen graft material. This osteocon-
ductive composite of hydroxyapatite, tricalcium phosphate,
and Type-I and III collagen is mixed with autologous bone
marrow to provide osteoprogenitor cells and other growth
factors. The composite does not provide structural support,
but it serves as an effective bone-graft substitute or bone-graft
expander to augment acute fracture-healing. Chapman et al.
performed a prospective, randomized comparison of autolo-
gous iliac crest bone graft and calcium-collagen graft material
in the treatment of acute long-bone fractures with both bone-
grafting (<30 cm
3
volume required) and internal or external
fixation
50
. The authors observed no differences between the
two groups with regard to the union rate or functional mea-
sures, and they concluded that calcium-collagen graft material
with autologous bone marrow can be used instead of autolo-
gous bone graft for patients who have an acute traumatic de-
fect of a long bone. There is no scientific evidence that
calcium-collagen graft materials can effectively substitute for
autologous bone graft to stimulate healing of nonunions. I
recommend the use of this material with autologous bone
marrow as a replacement for autologous bone graft for acute
long-bone fractures with enough comminution or cortical
bone loss to require bone-grafting when internal or external
fixation is planned. I do not recommend using it to fill meta-
physeal bone defects resulting from articular fractures because
it does not offer structural support. Finally, I do not recom-
mend it for the treatment of nonunions except in the role of a
bone-graft expander when the supply of autologous bone
graft is limited.
Calcium sulfate graft material with a patented crystal-
line structure described as an alphahemihydrate acts primarily
Fig. 3-A
Preoperative anteroposterior radiograph of a shotgun injury to the left
tibial plateau, which was previously debrided and stabilized in an exter-
nal fixator.
on March 30, 2006 www.ejbjs.org Downloaded from
oI
THE JOURNAL OF BONE & JOI NT SURGERY J BJ S. ORG
VOLUME 84-A NUMBER 3 MARCH 2002
BONE-GRAFTI NG AND
BONE-GRAFT SUBSTI TUTES
as an osteoconductive bone-void filler that completely resorbs
as newly formed bone remodels and restores anatomic fea-
tures and structural properties. Potential uses of calcium sul-
fate graft material include the filling of cysts, bone cavities,
and segmental bone defects; expansion of grafts used for spi-
nal fusion; and filling of bone-graft harvest sites. Currently,
very limited information is available on the use of this mate-
rial in humans; no published controlled studies are available,
to my knowledge.
Another option available for filling bone voids after
acute fractures is injectable calcium phosphate. One such
material, Skeletal Repair System (SRS; Norian, Cupertino,
California) is an injectable paste of inorganic calcium and
phosphate that hardens within minutes, forming a carbon-
ated apatite of low crystallinity and small grain size similar to
that found in the mineral phase of bone
51
. After twelve hours,
this material hardens to form dahlite with a compressive
strength of 55 MPa, and, because of its crystalline structure, it
can eventually be resorbed and replaced by host bone
51
. This
material may be useful as a bone-graft substitute to augment
cast treatment or internal fixation of impacted metaphyseal
fractures. One indication for use of such a material is an im-
pacted, extra-articular distal radial fracture that would nor-
mally require pinning after reduction to avoid dorsal settling.
At least one study has demonstrated that this calcium phos-
phate material can be injected into the fracture site after re-
duction, and after a few minutes a below-the-elbow cast is
applied
52
. After two weeks, the cast can be replaced by a volar
wrist splint until the fracture is healed
52
. Several authors have
reported promising results with this approach for distal radial
fractures
52-54
. However, while a multicenter study showed that
patients treated with injectable calcium phosphate and cast
immobilization had earlier functional return than patients
treated with cast immobilization or external fixation alone,
the advantage diminished by three months and no advantage
was detectable after one year
55
. Additional potential applica-
tions of injectable calcium phosphate materials include treat-
ment of hip
56
, spine, calcaneal, and other extra-articular
metaphyseal fractures at risk for hardware failure or for redis-
placement under compressive loads. Several injectable pastes
are available, but little data are available to make comparisons
based on clinical outcomes.
Fig. 3-B
Anteroposterior (Fig. 3-B) and lateral (Fig. 3-C) radiographs made ten months after fibular strut allogeneic bone-grafting of the massive metaphyseal
bone defect.
Fig. 3-C
on March 30, 2006 www.ejbjs.org Downloaded from
o:
THE JOURNAL OF BONE & JOI NT SURGERY J BJ S. ORG
VOLUME 84-A NUMBER 3 MARCH 2002
BONE-GRAFTI NG AND
BONE-GRAFT SUBSTI TUTES
Bioactive Glass
Several variations of glass beads called Bioglass (USBiomateri-
als, Alachua, Florida) are currently being developed, and one
formulation (PerioGlas) has been approved in the United
States for periodontal use. The beads are composed of silica
(45%), calcium oxide (24.5%), disodium oxide (24.5%), and
pyrophosphate (6%). When implanted, they bind to collagen,
growth factors, and fibrin to form a porous matrix to allow in-
filtration of osteogenic cells. The matrix provides some com-
pressive strength, but it does not provide structural support. I
have no experience with this material.
Authors Recommendations
for Specific Problems
The attainment of proper axial alignment and adequate sta-
bility and the preservation of vascular supply remain the most
important factors for successful treatment of acute fractures
as well as delayed unions and nonunions. In fractures that do
not heal or that heal slowly, there is an abnormality of either
the biology or the mechanical environment, or both. There-
fore, unless the mechanical environment of the fracture site is
optimized, usually by increasing the stability of the fracture,
manipulation of the biology at the fracture site with bone
graft or bone-graft substitute will have limited success. In
cases of hypertrophic nonunion, successful healing can usu-
ally be accomplished simply by stabilizing the fracture. If the
mechanical environment has been optimized and a nonunion
still exists, the next step for the surgeon is to choose an appro-
priate grafting material depending on the biology of the frac-
ture site.
The first step in matching the graft to the clinical prob-
lem is to decide whether the problem is a lack of osteoinduc-
tion and/or osteogenesis or one of structural bone loss
requiring a load-bearing graft. Well-contained, stable meta-
physeal defects with a good vascular supply are well suited for
osteoconductive bone-graft substitutes that can resist com-
pressive forces. Allograft chips or any of the calcium-based
bone-graft substitutes would be appropriate in this setting. If a
nonunion is present and a stimulus for new bone formation is
needed, an autologous cancellous graft is ideal. There is no bi-
ologic rationale for using a purely osteoconductive graft in a
nonunion or delayed union that requires new bone formation
or when the vascularity of the grafting bed is marginal. Autol-
ogous cancellous bone or composite grafts of demineralized
bone matrix and bone marrow, or demineralized bone matrix
and one of the calcium-based substitutes, are appropriate in
these situations.
If a diaphyseal defect is too large to heal reliably with
cancellous bone-grafting, then a structural graft such as a cor-
tical autograft or allograft may be needed. For these large de-
fects (approximately 6 cm in my experience), vascularized
cortical autografts are a better choice than nonvascularized
autografts or allografts because of their more rapid and com-
plete incorporation as well as their ability to hypertrophy.
Cortical allografts are best reserved for use in areas with an
excellent vascular supply (such as metaphyseal locations [Figs.
3-A, 3-B, and 3-C] or around the femur), whereas vascular-
ized cortical autografts should be reserved for use in areas of
marginal blood supply (such as the scaphoid, femoral neck, or
talus) or for reconstructing diaphyseal segmental bone de-
fects. For smaller defects (<6 cm), autologous cancellous bone
used with stable internal fixation is adequate for nonunions or
fresh fractures with bone loss.
Although gender has no bearing on the choice of which
graft to use, the age of the patient should be taken into consid-
eration. Skeletally immature patients rarely have nonunion of
acute injuries, but they may require bone-grafting after the
removal of a benign or malignant bone tumor or for another
TABLE III Calcium-Based Bone-Graft Substitutes Cleared for Marketing in the United States or Europe
Product Company Type
Collagraft Zimmer Bovine collagen, hydroxyapatite, and
tricalcium phosphate; available in granular
and strip forms
Pro Osteon Interpore Cross Coralline hydroxyapatite granules and blocks;
200, 500, and R forms
Osteoset Wright Medical Technology Calcium sulfate pellets
Allomatrix Wright Medical Technology Demineralized human bone matrix in an
Osteoset medium
NovaBone (approved in Europe;
planned for United States)
USBiomaterials Bioactive glass (SiO
2
and minerals)
Endobon (approved in Europe,
not United States)
Merck KGaA Sintered bovine cancellous bone blocks
Vitoss Orthovita Ultraporous beta-tricalcium phosphate
SRS Norian Calcium phosphate (carbonated apatite)
injectable cement
on March 30, 2006 www.ejbjs.org Downloaded from
o,
THE JOURNAL OF BONE & JOI NT SURGERY J BJ S. ORG
VOLUME 84-A NUMBER 3 MARCH 2002
BONE-GRAFTI NG AND
BONE-GRAFT SUBSTI TUTES
condition such as congenital pseudarthrosis of the tibia. Most
benign tumors require some type of bone to fill the defect fol-
lowing curettage. In skeletally immature patients, the volume
of autogenous bone graft available in the iliac crests is limited.
Therefore, these patients are potential candidates for treat-
ment with demineralized bone matrix, allograft cancellous
bone, or another osteoconductive void-filling bone-graft
substitute. At present, there are limited data to support the use
of demineralized bone matrix in combination with freshly
harvested bone marrow in children.
Christopher G. Finkemeier, MD
Department of Orthopaedic Surgery, University of California Davis Med-
ical Center, 4860 Y Street, Suite 3800, Sacramento, CA 95817
The author did not receive grants or outside funding in support of his
research or preparation of this manuscript. He did not receive payments
or other benefits or a commitment or agreement to provide such benefits
from a commercial entity. No commercial entity paid or directed, or
agreed to pay or direct, any benefits to any research fund, foundation,
educational institution, or other charitable or nonprofit organization
with which the author is affiliated or associated.
References
1. Sauer HD, Schoettle H. The stability of osteosyntheses bridging defects. Arch
Orthop Trauma Surg. 1979;95:27-30.
2. Younger EM, Chapman MW. Morbidity at bone graft donor sites. J Orthop
Trauma. 1989;3:192-5.
3. Axhausen W. The osteogenetic phases of regeneration of bone. A historical
and experimental study. J Bone Joint Surg Am. 1956;38:593-600.
4. Axhausen W. Die Knochenregenerationein Zweiphasisches Geschehen.
Zentralble Chir. 1952;77:435-42.
5. Gray JC, Elves MW. Early osteogenesis in compact bone isografts: a quan-
titative study of contributions of the different graft cells. Calcif Tissue Int.
1979;29:225-37.
6. Heslop BF, Zeiss IM, Nisbet NW. Studies on the transference of bone.
I. A comparison of autologous and homologous bone implants with refer-
ence to osteocyte survival, osteogenesis and host reaction. Br J Exp Pathol.
1960;41:269-87.
7. Burwell RG. Studies in the transplantation of bone. VII. The fresh composite
homograft autograft of cancellous bone. An analysis of factors leading to os-
teogenesis in marrow transplants and in marrow-containing bone grafts.
J Bone Joint Surg Br. 1964;46:110-40.
8. Williams R. Comparison of living autografts and homogenous grafts of cancel-
lous bone heterotopically placed in rabbits. Anat Rec. 1962;143:93-105.
9. Vainio S. Observation on the regeneration of an autogenous transplant of the
bone. Acta Chir Scand. 1950;100:86-109.
10. Einhorn TA, Majeska RJ, Rush EB, Levine PM, Horowitz MC. The expression
of cytokine activity by fracture callus. J Bone Miner Res. 1995;10:1272-81.
11. Gazdag AR, Lane JM, Glaser D, Forster RA. Alternatives to autogenous bone
graft: efficacy and indications. J Am Acad Orthop Surg. 1995;3:1-8.
12. Dell PC, Burchardt H, Glowczewskie FP Jr. A roentgenographic, biomechani-
cal, and histological evaluation of vascularized and non-vascularized segmen-
tal fibular canine autografts. J Bone Joint Surg Am. 1985;67:105-12.
13. Doi K, Tominaga S, Shibata T. Bone grafts with microvascular anastomosis of
vascular pedicles: an experimental study in dogs. J Bone Joint Surg Am.
1977;59:806-15.
14. Enneking WF, Burchardt H, Puhl JJ, Piotrowski G. Physical and biological
aspects of repair in dog cortical-bone transplants. J Bone Joint Surg Am.
1975;57:237-52.
15. Wolff J. Das Gaesetz der Transformation der Knochen. Berlin: A. Hirschwald;
1892.
16. Tang CL, Mahoney JL, McKee MD, Richards RR, Waddell JP, Louie B.
Donor site morbidity following vascularized fibular grafting. Microsurgery.
1998;18:383-6.
17. Green SA. Skeletal defects. A comparison of bone grafting and bone trans-
port for segmental skeletal defects. Clin Orthop. 1994;301:111-7.
18. Duman H, Sengezer M, Celikoz B, Turegun M, Isik S. Lower extremity sal-
vage using a free flap associated with the Ilizarov method in patients with
massive combat injuries. Ann Plast Surg. 2001;46:108-12.
19. Connolly JF. Injectable bone marrow preparations to stimulate osteogenic re-
pair. Clin Orthop. 1995;313:8-18.
20. Muschler GF, Boehm C, Easley K. Aspiration to obtain osteoblast progenitor
cells from human bone marrow: the influence of aspiration volume. J Bone
Joint Surg Am. 1997;79:1699-709. Erratum. 1998; 80:302.
21. Ohgushi H, Goldberg VM, Caplan AI. Repair of bone defects with marrow
cells and porous ceramic. Experiments in rats. Acta Orthop Scand.
1989;60:334-9.
22. Lindholm TS, Urist MR. A quantitative analysis of new bone formation by in-
duction in compositive grafts of bone marrow and bone matrix. Clin Orthop.
1980;150:288-300.
23. Jackson IT, Scheker LR, Vandervord JG, McLennan JG. Bone marrrow graft-
ing in the secondary closure of alveolar-palatal defects in children. Br J Plast
Surg. 1981;34:422-5.
24. Greer E, Hinton C, Triffitt JT. The effect of decalcified bone matrix on the os-
teogenic potential of bone marrow. Clin Orthop. 1986;205:292-8.
25. Connolly JF, Guse R, Tiedeman J, Dehne R. Autologous marrow injection
as a substitute for operative grafting of tibial nonunions. Clin Orthop.
1991;266:259-70.
26. Tiedeman JJ, Garvin KL, Kile TA, Connolly JF. The role of a composite, de-
mineralized bone matrix and bone marrow in the treatment of osseous
defects. Orthopedics. 1995;18:1153-8.
27. Harkins HW, Phemister DB. Simplified technic of onlay grafts for all ununited
fractures in acceptable position. JAMA. 1937;109:1501-6.
28. Hanson LW, Eppright RH. Posterior bone-grafting of the tibia for non-union: a
review of twenty-four cases. J Bone Joint Surg Am. 1966;48:27-43.
29. Jones KG, Barnett HC. Cancellous-bone grafting for non-union of the
tibia through the posterolateral approach. J Bone Joint Surg Am.
1955;37:1250-60.
30. Stegemann P, Lorio M, Soriano R, Bone L. Management protocol for un-
reamed interlocking tibial nails for open tibial fractures. J Orthop Trauma.
1995;9:117-20.
31. Urist MR, Silverman BF, Buring K, Dubuc FL, Rosenberg JM. The bone induc-
tion principle. Clin Orthop. 1967;53:243-83.
32. Urist MR, Dawson E. Intertransverse process fusion with the aid of chemo-
sterilized autolyzed antigen-extracted allogenic (AAA) bone. Clin Orthop.
1981;154:97-113.
33. Reddi AH, Huggins C. Biochemical sequences in the transformation of
normal fibroblasts in adolescent rats. Proc Natl Acad Sci U S A. 1972;
69:1601-5.
34. Aspenberg P, Johnsson E, Thorngren KG. Dose-dependent reduction of
bone inductive properties by ethylene oxide. J Bone Joint Surg Br. 1990;
72:1036-7.
35. Munting E, Wilmart JF, Wijne A, Hennebert P, Delloye C. Effect of steriliza-
tion on osteoinduction. Comparison of five methods in demineralized rat
bone. Acta Orthop Scand. 1988;59:34-8.
36. AATB information alert. McLean, VA: American Association of Tissue
Banks; 1993.
37. Upton J, Glowacki J. Hand reconstruction with allograft demineralized
bone: twenty-six implants in twelve patients. J Hand Surg [Am]. 1992;
17:704-13.
38. Whiteman D, Gropper PT, Wirtz P, Monk P. Demineralized bone powder.
Clinical applications for bone defects of the hand. J Hand Surg [Br].
1993;18:487-90.
39. Hu X, Yao L, Lu C, Wang S, Chen Y. Experimental and clinical investigations
of human insoluble bone matrix gelatin. A report of 24 cases. Clin Orthop.
1993;293:360-5.
40. Kakiuchi M, Hosoya T, Takaoka K, Amitani K, Ono K. Human bone matrix
on March 30, 2006 www.ejbjs.org Downloaded from
o
THE JOURNAL OF BONE & JOI NT SURGERY J BJ S. ORG
VOLUME 84-A NUMBER 3 MARCH 2002
BONE-GRAFTI NG AND
BONE-GRAFT SUBSTI TUTES
gelatin as a clinical alloimplant. A retrospective review of 160 cases. Int
Orthop. 1985;9:181-8.
41. Johnson EE, Urist MR, Finerman GA. Resistant nonunions and partial or
complete segmental defects of long bones. Treatment with implants of a
composite of a human bone morphogenetic protein (BMP) and autolyzed,
antigen-extracted, allogeneic (AAA) bone. Clin Orthop. 1992;277:229-37.
42. Tiedeman JJ, Connolly JF, Strates BS, Lippiello L. Treatment of nonunion by
percutaneous injection of bone marrow and demineralized bone matrix. An
experimental study in dogs. Clin Orthop. 1991;268:294-302.
43. Prewett AB, Moyer MP, OLeary RK, Mellonig JT. Decalcification inactivates
HIV in spiked and infected bone. Trans Orthop Res Soc. 1992;17:436.
44. Osteotech, Eatontown, New Jersey. www.osteotech.com.
45. Musculoskeletal Transplant Foundation, Edison, New Jersey. www.mtf.org.
46. Jarcho M. Calcium phosphate ceramics as hard tissue prosthetics. Clin
Orthop. 1981;157:259-78.
47. Bucholz RW, Carlton A, Holmes RE. Hydroxyapatite and tricalcium phos-
phate bone graft substitutes. Orthop Clin North Am. 1987;18:323-34.
48. Hollinger JO, Brekke J, Gruskin E, Lee D. Role of bone substitutes. Clin
Orthop. 1996;324:55-65.
49. Bucholz RW, Carlton A, Holmes R. Interporous hydroxyapatite as a bone
graft substitute in tibial plateau fractures. Clin Orthop. 1989;240:53-62.
50. Chapman MW, Bucholz R, Cornell C. Treatment of acute fractures with a
collagen-calcium phosphate graft material. A randomized clinical trial.
J Bone Joint Surg Am. 1997;79:495-502.
51. Constantz BR, Ison IC, Fulmer MT, Poser RD, Smith ST, VanWagoner M,
Ross J, Goldstein SA, Jupiter JB, Rosenthal DI. Skeletal repair by in situ for-
mation of the mineral phase of bone. Science. 1995;267:1796-9.
52. Jupiter JB, Winters S, Sigman S, Lowe C, Pappas C, Ladd AL, Van Wagoner
M, Smith ST. Repair of five distal radius fractures with an investigational can-
cellous bone cement: a preliminary report. J Orthop Trauma. 1997;11:110-6.
53. Kopylov P, Jonsson K, Thorngren KG, Aspenberg P. Injectable calcium
phosphate in the treatment of distal radial fractures. J Hand Surg [Br].
1996;21:768-71.
54. Kopylov P, Runnqvist K, Jonsson K, Aspenberg P. Norian SRS versus exter-
nal fixation in redisplaced distal radial fractures. A randomized study in 40
patients. Acta Orthop Scand. 1999;70:1-5.
55. Norian SRS. In: Orthopaedic and rehabilitation devices panel. Federal
Drug Administration. p 3463t2.pdf. www.fda.gov/ohrms/dockets/ac/
cdrh98t.htm#.
56. Goodman SB, Bauer TW, Carter D, Casteleyn PP, Goldstein SA, Kyle RF,
Larsson S, Stankewich CJ, Swiontkowski MF, Tencer AF, Yetkinler DN,
Poser RD. Norian SRS cement augmentation in hip fracture treatment. Labo-
ratory and initial clinical results. Clin Orthop. 1998;348:42-50.
57. Ray RD. Vascularization of bone grafts and implants. Clin Orthop. 1972;
87:43-8.
58. Enneking WF, Mindell ER. Observations on massive retrieved human al-
lografts. J Bone Joint Surg Am. 1991;73:1123-42.
59. Stevenson S. Enhancement of fracture healing with autogenous and alloge-
neic bone grafts. Clin Orthop. 1998;355 Suppl:S239-46.
on March 30, 2006 www.ejbjs.org Downloaded from