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CHAPTER 22/ENDOSCOPIC ANTERIOR LUMBAR PROCEDURES / 243
VASCULAR INJURIES
The occurrence of vascular injuries should def initely
be a primary concern for the use of the endoscopic
approach. The literature seems to sho w a higher incidence
of vascular injuries with endoscopic surgery than with the
open approach. With the transperitoneal video-assisted
approach the following vascular injury rates have been
reported: McAfee (26) (1/22; 4.5%), Mathews et al. (3)
(1/6; 17%), Zuckerman et al. (2) (2/17; 12%), Mahvi and
Zdeblick (9) (2/20; 10%), Regan et al. (14) (5/58; 9.5%),
Lieberman et al. (15) (1/47; 2.1%), Regan et al. (4) (6/24;
25%), and Escobar et al. (23) (2/34; 5.9%). In the videoassisted retroperitoneal gasless approach, reported vascular injury rates were as follows: Escobar (23) (0/30
patients), Onimus et al. (24) (0/20), and Thalgott et al.
(27) (8/98; 8.1%).
Mini-laparotomy, an alternative minimal access approach has also been associated with vascular injuries.
Escobar et al. (23) report two vascular injuries in 51
patients (4%), Mayer (28) reported none in 25 patients,
Baker et al. (29) reported 18.4% in 19 patients. Vascular
injuries have also been reported in traditional open
approaches; however, the incidence appears to be much
lower. Faciszewski et al. (30) reported only one major
vessel injury in 350 anterior lumbar procedures (0.08%);
Baker et al. (29) reported a 7.7% rate in 26 patients for
this approach.
Vascular injuries may in v olv e b leeding from small v essels or injury to the major vessels. It is important to ligate all bleeding vessels. Specialized equipment has been
made for clipping vessels in surgeries where transperitoneal with insufflation approach is used. In the gasless
approach, the conventional hemo-clips can be used.
Injury to the major vessels requires immediate control of
bleeding and if any difficulty is encountered, it is recommended to proceed with conversion to a conventional
open approach as quickly as possible.
Anatomic variations increase incidence of vascular
injuries and these occur most frequently at the L4-5 lev el.
Zdeblick has described the incidence of vessel injuries
and retrograde ejaculations at the L4-5 level. It is thought
to be related to the vascular anatom y, especially the bifurcation of the aorta and the inferior vena cava (9,10,29,
31–34). Most often, the aorta and vena cava divide on the
L5 vertebral body and exposure of the L4-5 disc is made
above. However, at times the bifurcation is high and the
L4-5 exposure more difficult. Sometimes it is easier to
expose from below the bifurcation, but tears to the left
common iliac vein are more common. We use the tenet
that “it is easier to avoid bleeding than it is to stop it.” In
this case bleeding is best avoided by gently retracting the
vein and observing sites of fixation by lar ge branches that
will tear with further retraction. Preemptive clipping and
dividing of the L4 segmental lumbar artery and vein and
the ascending iliolumbar vein is prudent if not necessary.
Retrograde Ejaculation
In Regan’s series (35) in which he compared open techniques with laparoscopic techniques, the authors report
that retrograde ejaculation occurred in 9.4% of laparoscopic cases compared to 4.7% of open cases. Complications of retrograde ejaculation vary between 0.42% and
45% of cases (12,34,36,37).
Retrograde ejaculation results from injury to the superior hypogastric plexus, which controls bladder-neck closure during ejaculation. The incidence reported varies
between 0.42% and 45% of cases (13,14,34,38). The
majority of these are thought to be transient. Retrograde
ejaculation has been reported with open ALIF in 0.42%
to 22% of cases (13,14,34,39,40). In Flynn’s series (4,500
cases), 25% of patients reported retrograde ejaculation
and had spontaneous resolution (39).
The superior hypogastric plexus lies in the retroperitoneal connective tissue anterior to the distal aorta and
aortic bifurcation. It lies slightly to the left of the midline
before dividing into the left and right hypogastric plexus.
It is therefore most vulnerable with direct dissection from
anterior and left-sided dissection. The retroperitoneal
approach is usually done from the left side and is usually
more posterior to the hypogastric plexus. This would
explain why they are fewer patients with retrograde ejaculation (41).
Kleeman (16) recommends careful analysis of the vascular anatomy, especially at the L4-5 le vel and has classified the vascular anatomy at this area so that appropriate
surgical approaches can be planned. This would reduce
exposure on the side of the aorta and thus the hypogastric
plexus. It is also recommended that bipolar cauterization
be used.
Loss of Orientation
Loss of orientation regarding the center of the disc and
the midline has been described in laparoscopic transperitoneal techniques and it is more difficult to identify during the procedure under visualization of a scope due to
limitation of the exposure and orientation of the camera.
Loss of orientation can lead to asymmetric graft/cage
placement. If placement is too lateral, then foraminal
encroachment or vessel injury is a risk. It is therefore
important to use X-rays in two planes.
Pseudoarthrosis
The most common cause for reoperation of interbody
fusion cages is pseudoarthrosis. Salvage includes instrumented posterolateral fusions and frequent remov al of the
interbody device and replacement with autograft or allograft (42). This complication of pseudoarthrosis is seen
more commonly in procedures where a trephine c ylindric
core of disc was removed and it is recommended that a
244 /SECTION IV/SURGERY
complete discectomy would decrease the chances of
nonunion. Studies using bone morphogenic protein
(BMP) have shown remarkably high fusion rates.
Iatrogenic Nerve Root Impingement
This complication occurs due to disc herniation or
retropulsed bone although it is not unique to endoscopic
techniques, as described (23, 26). Neurologic problems
including the radicular type of pain appeared to be unique
to the transperitoneal insufflation technique. Regan et al.
(14) reported six such cases in among 215 patients (2.8%),
and a reoperation rate of 2.3% for nerve root decompression. Escobar et al. (23) reported six patients, all with
transperitoneal insufflation approach for an incidence of
18% (6/34). All of these had undergone cylindric trephine
discectomies and insertion of a screw-in cage device. One
of the six patients had an acute cauda equina syndrome
secondary to an acute disc herniation requiring emergent
posterior decompression, which resulted in full neurologic
recovery. Four of the six patients with new onset radicular
symptoms had spontaneous resolution of the symptoms
within 6 months after the index procedure.
Postoperative Ileus
Some degree of postoperative ileus is normal and to be
expected after any surgery and anesthetic, even nonabdominal procedures (43). The degree of ileus is generally
proportional to the extent of surgery, the amount of
intestinal manipulation, the quantity of residual intraperitoneal blood or hematoma, the severity of physiologic
disruption or infection, and the specif ic sensitivity of the
individual patient. Paying strict attention to all these matters is important in avoiding extensive ileus. It has been
shown that typical laparoscopic surgery is associated
with less postoperative ileus than with comparable open
procedures. The difference in ileus between mini-open
spine access and the endoscopic exposure has not been
specifically investigated. Unless the length of laparoscopic procedures can be decreased to that it compares
with open procedures, it is unlikely to be much different.
Hernias
Hernias at the trocar site are a rare complication and
occur more commonly in transperitoneal than in retroperitoneal endoscopy (26). This can be avoided by placing a stitch in the fascia of all ports greater than 10 mm
in size.
Ureteral Injuries
The ureter is at risk for injury during anterior exposure
of the lumbar spine and this may be higher with minimal
access approaches. Escobar et al. (23) reported two
(2/135; 1.5%) injuries: one with video-assisted extraperitoneal approach and one with a mini-laparotomy approach. There have been numerous single case reports
regarding ureteral injuries with anterior lumbar surgery.
Faciszewski et al. (30) has reported one case in a series of
350 traditional open approaches for an instance of 0.3%.
Laparoscopic Conversion
Conversion to an open approach may be due to vascular
injury , abdominal adhesions, organ injury, or technical difficulties. Conversion should not be considered a failure.
COMPARISON OF MINI OPEN TECHNIQUE TO
ENDOSCOPIC OPEN ALIF
The advantages of minimally invasive techniques are
intended to reduce postoperative morbidity and decrease
hospital stay. There should be no increase in complications of the approach and the outcomes should be comparable to traditional open approaches. The mini open
technique offers many of the same advantages as the
laparoscopic techniques. Mayer (28) has been credited
for describing this approach. In contrast to standard
laparotomy, this technique uses a muscle-splitting
approach, separating muscles in the direction of the fiber
orientation.
Another technique or approach is a vertical midline
incision and division of the left rectus sheath in a vertical
direction. The rectus muscle is retracted laterally and the
posterior sheath is incised vertically as well. The preperitoneal plane is developed bluntly, first laterally and then
posteriorly. Thereafter, the operation continues as with
standard lateral open approaches.
Zdeblick and David reported a comparison of 25 anterior laparoscopic approaches with 25 mini open techniques for L4-5 fusion. Paired threaded cages were used
in both cases. Operating time, blood loss, and length of
hospital stay sho wed no statistical difference. There w as a
lower rate of complications in the mini open group (4%)
versus a higher rate (20%) in the laparoscopic group. This
study shows that even in technically competent hands
laparoscopy has no advantage to a mini approach (34).
There was significant increase in surgical time in the
laparoscopic group when two-le vel procedures were evaluated (180 minutes versus 160 minutes).
Escobar et al. (23) reported on a retrospective review
comparing 135 patients undergoing four different
approaches: transperitoneal video-assisted surgery with
insufflation, retroperitoneal endoscopic video-assisted
surgery, mini laparotomy, retroperitoneal approach, and
traditional oblique retroperitoneal surgery. There was
onset of new radicular pain or numbness not experienced
by the patient prior to surgery in six patients (18%); all
with transperitoneal video-assisted surgery using insufflation. Vascular problems occurred in f ive patients (3%
CHAPTER 22/ENDOSCOPIC ANTERIOR LUMBAR PROCEDURES / 245
overall); two in the transperitoneal video-assisted group
(5.9%) and three in the mini-laparotomy group (8.7% of
the group). Retrograde ejaculation occurred in four of 50
male patients (8%); three in the transperitoneal videoassisted group (25%) and one in the mini-laparotomy
group (2%). Two patients had ureteral injuries (1.5%
overall); one each in the retroperitoneal endoscopic and
mini- laparotomy groups. Conversion to open procedures
was performed in seven patients (11% of the videoassisted procedures).
The reasons for conversion included two major vessel
lacerations and five peritoneal tears in the retroperitoneal
video-assisted group. Overall, the incidence of complications in the endoscopic group was consistent with the literature for video-assisted techniques; it was thought to be
higher than for open techniques. Reports in the literature
do not show any advantage of laparoscopic versus miniopen for anterior lumbar surgery (34, 40).
In reviewing the literature, it would appear that the
laparoscopic insufflation technique is associated with a
higher rate of vascular injuries. These injuries usually
require conversion to an open procedure, thus prolonging
surgical time. However, vascular injuries occur with all
approaches and successful vascular repair was the standard outcome for the aforementioned cited literature.
interbody fusion (PLIF) or the recently popularized
translumbar interforaminal fusion (TLIF) and should be
considered less invasive if they save the need for additional anterior access. Dural injury and epidural scarring
however are a high risk. Image-guided interbody fusions
and instrumentation have been a further development of
the minimally invasive posterior approach.
Malberg et al. (45) have described a direct lateral
approach to the spine employing minimal access. A small
incision is used and a working channel is docked on the
disc space after a series of dilators have prepared access
through a psoas muscle–splitting approach. A guide
frame coupled with X-rays provides image guidance to
accurate placement of the dilators and working channel.
An electromyogram neuromonitoring system is used to
provide increased safety from nerve injury to the lumbar
plexus. However, there have been no extensive reports on
the clinical experience with this approach.
We have found many of the techniques and limitations
of endoscopic approaches to be cumbersome and most
often use mini open procedures. This has been especially
true in multilevel fusions. The balance of benef its and
drawbacks will continue to tip in favor of endoscopic
approaches as technological advances continue to eliminate the problems.
CONCLUSION
Minimizing access to the spine will remain a goal in
spine surgery. Current techniques have some drawbacks,
but should be regarded as a stepping stone to the future.
There are good studies using prospective randomized
controls, but no good outcome studies are described for
fusion outcomes. These studies are necessary to establish
superiority of any technique. The need for more minimally in vasi v e techniques will al w a ys be there. The use of
BMP and other materials to substitute for the patient’s
own bone ha ve already reduced the need for harvesting of
bone graft and lend themselves to easy implantation, thus
making endoscopic techniques more attractive.
Evaluation of fusion by standard radiographs is unreliable. Thin section CTs with three-dimensional reconstruction are more reliable. CTs are usually performed
when there is a suspicion of pseudoarthrosis or nonunion,
or for evaluation of pain. There are few studies reporting
CT evaluation of all patients in a laparoscopic cohort.
Pellise et al. described a 16.6% fusion rate in patients
fused with carbon fiber cages using laparoscopic techniques with complete discectomy (44). There was significant improvement in clinical outcomes ho w e v er at a minimum follow-up of 2 years.
Fusion surgery comprises a large volume of spine
surgery, and interbody fusions have become widely popular. The access for interbody fusions can be performed
anteriorly or posteriorly. Interbody fusions through a posterior approach include a conventional posterolateral
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CHAPTER 23
Biology of Bone Grafting: Autograft and Allograft
Robert Gunzburg and Marek Szpalski
Spinal fusion is a well-accepted procedure for the treatment of disorders such as trauma, deformity, tumor,
inflammation or infection, and common degenerative
pathology. The aim of a spinal fusion is to eliminate the
instability of the spine caused by these pathologies. By
definition, spinal fusion means the achievement of a bony
union between the involved vertebrae. In this chapter, the
two types of bone grafts that are derived from natural
bone (i.e., autograft and allograft) and are commonly
used to achieve this goal will be discussed.
Far from being an inert structure, bone tissue can modify its mass and morphology in response to local and hormonal factors, thereby meeting the functional demands
posed by various stimuli. Bone tissue also has the capacity for repairing itself without scarring. Bone grafting
makes use of these core characteristics. In order to make
optimal use of the clinically available graft options, the
biology of bone, including its capacity for remodeling
and self-repair, must be understood.
BONE STRUCTURE AND PHYSIOLOGY
Bone Cells
Osteoprogenitor cells are derived from mesenchymal
cells and line the internal and external surfaces of bone.
These cells have the capacity for differentiation into
osteoblasts and related cells (e.g., fibroblasts) that comprise connective tissue.
Osteoblasts are active secretory cells derived from
osteoprogenitor cells. Osteoblasts form the extracellular
bone matrix by secreting osteoid (unmineralized matrix)
and regulate its mineralization through the exocytosis
of alkaline phosphatase-containing vesicles. Osteoblasts
form a tight cell layer at the bone surface and have a life
span of up to 8 weeks. The production of matrix proteins
by osteoblasts decreases considerably with time, yet
osteoblasts remain in communication with each other and
with related cells (e.g., osteocytes) by elaborating cytoplasmic processes that penetrate surrounding osteoid and
terminate in gap junctions, creating an extensive intercellular communication network.
Osteocytes are derived from osteoblasts and comprise
90% of all cells in the mature skeleton; however, these
mature cells differ significantly from osteoblasts in their
biochemical, morphologic, and functional characteristics.
Osteocytes are smaller, contain fe wer organelles and have
a higher ratio of nucleus to cytoplasm. They elaborate
numerous filopodia, enabling interconnections and cellular communication. Occasionally, osteoblasts become
trapped in the extracellular matrix, resulting in stimuli
sufficient for their transformation into mature bone cells.
Ongoing studies of the mechanosensory properties of
osteocytes suggest that they are the primary regulators of
bone remodeling, orchestrating the formation and resorption of bone in response to mechanical demands (1).
Osteoclasts are multinucleated, highly migratory,
phagocytic cells derived from monocyte/macrophage
precursors. Osteoclasts are responsible for the resorption
of fully mineralized bone through acidic decalcification
of bone matrix, followed by lysosomally mediated hydrolysis of its organic components. An activated osteoclast can resorb bone matrix at the rate of 200,000 µm
per day. Interestingly, 7 to 10 generations of osteoblasts
are required to form this same amount of bone matrix (2).
Molecular Basis of Bone Remodeling
The regulation of osteoblastic and osteoclastic activities is dependent on a complex network of signaling molecules, including steroid hormones, prostaglandins, and
cytokines; the molecular basis of osteoblast-osteoclast
interactions is the subject of intensive research. The differentiation of osteoclast precursors into osteoclasts
requires the expression of osteoclast differentiation factor
3
247
248 /SECTION IV/SURGERY
(ODF; also known as RANKL, TRANCE, and OPGL), a
membrane-associated cytokine produced by osteoblasts
in response to osteotropic factors such as parathyroid hormone, vitamin D, and cytokines such as tumor necrosis
factor (TNF) and interleukins (3–5). Osteoclast precursors express the cell-surface receptor RANK, which
binds ODF through cellular interaction with osteoblasts,
in turn leading to osteoclast differentiation. ODF also
plays a key role in the activation of osteoclasts into
mature bone-resorbing cells (3). On the other hand, a
number of cell types have been shown to secrete a soluble decoy receptor, known as osteoclastogenesis inhibitory factor (OCIF, also known as osteoprotegerin, or
OPG) that competes for binding with RANK, thereby
inhibiting osteoclast formation and subsequent bone
resorption (5,3,6). The balance of molecular-signaling
events, such as those touched upon in this chapter, most
likely determine the outcome of stimuli leading to either
net bone formation or net bone resorption.
Extracellular Matrix
Mineralization of osteoid, which consists primarily of
collagen and ground substance, begins 10 to 15 days after
its formation (7). Initially, mineral content rises rapidly to
approximately 70% of its final amount; the remaining
30% being deposited over a period of several months.
Even after mineralization is complete, bone still contains
25% organic matrix, including cells. Hydroxyapatite
[Ca10(PO4)6(OH)3], the bone mineral, accounts for 70%
of the final weight, while water accounts for the remaining 5%. Proteins, such as bone morphogenic proteins
(BMP), growth factors, and cytokines, are embedded in
the remaining extracellular matrix and play an important
role in the mineralization process.
where stresses require its presence, and bone is absorbed
where stresses do not require it.
Osteoinduction
In addition to differentiated bone cells such as osteoblasts, osteoclasts, and osteocytes, bone and adjacent tissue contain a number of less differentiated cells. Osteoinduction is the process by which these less differentiated,
yet pluripotent cells are stimulated to develop into the
bone-forming cell lineage (8). A great deal of research
has focused on BMPs as inducing agents. BMPs are soluble glycoproteins (9) released in response to trauma,
such as a fracture, or physical stimuli, such as mechanical, electrical, or magnetic alterations. Although osteoblasts present at the site of injury participate in the healing of a fracture, bone and soft tissue injuries are the
primary trigger for the transformation of undifferentiated
cells into osteoblasts. The response to injury involves the
coordinated involvement of vascular and nervous tissue,
as well as the sensitization of precursor cells, leading to
the production of growth factors by these cells and their
differentiation into actively remodeling cell types (8,10).
Insofar as bone formation necessitates an adequate blood
supply, bone growth factors are also angiogenic (11).
Osteoconduction
Osteoconduction is the appositional growth of bone on
the three-dimensional surface of a suitable scaffold (12).
This includes the ingrowth of capillaries, periv ascular tissue, and osteoprogenitor cells and follows a highly organized, predictable spatial pattern (13).
Osteogenesis
Bone Architecture
The matrix of mature cortical and cancellous bone has
a lamellated structure. The lamellae run parallel to the
trabeculae of cancellous bone or concentrically surround
the Haversian canal in cortical bone, forming the socalled osteon, or functional unit of cortical bone. Typically, the long axis of the osteon runs parallel to the long
axis of the bone. Osteons evolve into secondary osteons
or haversian systems by resorption of preexisting bone.
Modeling is the process whereby bone is laid down onto
a surface without necessarily being preceded by resorption. Osteoblastic activity that fills voids following osteoclastic activity is referred to as remodeling. In the adult
skeleton, remodeling is the more active process and gives
bone the capacity to adapt to changes in loading and
metabolic stimuli. Indeed, bone tissue adapts to mechanical stimuli (compression and bending movements)
according to Wolff’s law, which states, bone is laid down
Osteogenesis is the process of bone formation through
cellular osteoblastic activity. Osteogenesis is dependent
upon osteoconduction as a matrix for the delivery of the
osteoinductive factors needed for the differentiation of
osteoprogenitor stem cells.
SPINAL FUSION
Osseous spinal fusion remains the ultimate goal in the
treatment of numerous spinal conditions. In spite of
improvements in surgical techniques and instrumentation, failure (nonunion) has been estimated to occur in
5% to 35% of patients undergoing single-level fusions,
and more frequently in patients undergoing multilevel
fusions (14). The rate of clinical success does not necessarily parallel the rate of fusion. Numerous factors, such
as mechanical stability, type of instrumentation, type of
bone graft material, and individual biological factors,
influence fusion rates.
CHAPTER 23/BIOLOGY OF BONE GRAFTING: AUTOGRAFT AND ALLOGRAFT / 249
Spinal arthrodesis can be achieved anteriorly by the
fusion of vertebral bodies. This became a standard procedure in the cervical spine soon after Cloward first advocated this approach as a treatment for ruptured discs (15).
At the levels of the thoracic and upper-lumbar spine, the
approach is more difficult due to the presence of the rib
cage and diaphragm; nonetheless, spinal interbody fusion
can still be accomplished at these levels. Below the level
of the conus, interbody fusion can be achieved either
through an anterior or posterior approach.
Spinal arthrodesis can also be achieved posteriorly by
bone bridging between the transverse processes and facet
joints of the vertebrae involved in the fusion. All these
fusion techniques are often combined with a variety of
internal fixation devices. The choice of approach and
technique depends on the type and location of the pathology and the surgeon’s experience and knowledge.
BONE GRAFTS
Bone is a commonly transplanted tissue. Bone grafts
have to promote osteogenesis and, in some applications,
may need to provide mechanical support. The morphology of the required graft depends on the type of fusion
being sought. Cortical bone is typically used for fixation
and support, whereas cancellous bone provides osteogenic potential (16). For cervical interbody fusion or
reconstruction or for thoracic and lumbar interbody
fusions and reconstructions, corticocancellous grafts are
required to provide structural support. However, when
stabilizing devices such as cages are being used, cancellous bone chips (particulate grafts) may be preferred. Particulate graft materials may also be preferred for posterior and posterolateral intervertebral fusions. Cancellous
bone grafts have been used to stimulate bone regeneration under a variety of pathologic circumstances, including trauma, infection, congenital defects, tumor invasion,
and degenerative diseases. For optimal remodeling of
bony tissue, these grafts need to mimic the properties of
cancellous bone, providing the interrelated characteristics
of osteoconduction, osteoinduction, and osteogenesis.
Revascularization occurs more rapidly with particulate
grafts than with structural grafts. Par ticulate bone grafts
tend to remodel entirely with time, whereas structural
(cortical) grafts have a tendency to retain their shape and
contain a mixture of necrotic and viable bone (17). The
process of creeping substitution, “the temporal and spatial repair activities whereby viable new bone replaces
necrotic old bone” (18), is also thought to differ between
cancellous and cortical allograft (17). Whereas creeping
substitution of cancellous bone involves appositional
bone formation followed by resorption, this order of
events is reversed for cortical bone, with osteoclastic
activity initiating the repair process (17,18). Such differences in the biology of remodeling between different
types of grafts may lead to significant differences in their
clinical applications (17).
Autograft
Autografts are grafts harvested from the patient at the
time of surgery. The autograft is the “gold standard” by
which the success of other grafting techniques is
assessed. Spinal fusion is the most common reason for
the harvest of autogenous bone (19). The main source of
autograft is the iliac crest, yet other sources, such as the
proximal tibia, the fibula, or a rib, can be used if the iliac
crest is not an option. Iliac crest bone can be harvested in
the form of cancellous bone chips, respecting the inner
and outer tables of the crista, or as tricortical strut grafts,
providing bone capable of structural suppor t (Fig. 23-1).
Cancellous bone autografts offer a number of positive
features including histocompatibility, which precludes the
risk of graft encapsulation and associated inflammation.
Moreover, autografts maintain viable osteoblasts and
osteoprogenitor cells, and also confer osteoconductive and
osteoinductive potential (19,20). The calcified matrix of
mature bone and its organic components (e.g., collagen
and ground substance) supply the graft with biocompatible, osteoconductive properties (19). Noncollagenous
growth factors, the most thoroughly investigated of which
are the BMPs, are primarily responsible for the osteoinductive capacity of autograft (21). The highly porous, trabecular structure of autogenous cancellous bone permits
the ingrowth of blood vessels needed for bone growth and
reduces the risk of complications from hypoxia. Finally,
autograft does not pose a risk of disease transmission.
Autograft procedures show a high rate of success for certain spinal fusions, such as posterior-cervical arthrodesis.
FIG. 23-1. Common types of iliac crest bone grafts. (From
Sandhu HS, Grewal HS, Parvataneni H. Bone grafting for
spinal fusion. Orthop Clin Nor th Am 1999;30:686, with permission.)
250 /SECTION IV/SURGERY
Autograft, however, has several drawbacks, including
both surgical complications and its limited supply. Although transplanted donor cells most likely contribute to
new bone growth, most of the osteogenic cells that repopulate the graft are thought to migrate from the fusion bed
(12,19). Although transplanted cells are initiall y aliv e, graft
viability is diminished when the graft tissue is separated
from its blood supply (19), leading to ischemic or apoptotic
cell death (12) and leaving behind only a bone mineral
scaffold (22). Although morselization may increase bone
graft surface area, leading to increased accessibility of
osteoinductive and osteogenic factors (19), additional
processing of autogenous bone may contribute to further
decreases in cell viability. The surviving cells receive their
oxygen and nutrients by diffusion only; thus, cells are
likely to die from ischemia before the graft is vascularized.
Rapid vascularization of the graft site may be impeded by
fibrin formation in the autograft and by the packing procedure used to place the graft into the surgical site; this is particularly of concern within the innermost region of the
graft. Autogenous bone viability is further complicated by
donor variables such as the age, gender, genetic makeup,
and physical health of the patient.
Harvest of autogenous tissue is associated with high
donor-site morbidity and is estimated to occur in 10% to
39% of patients (23). Donor-site morbidity is dependent
upon the surgical approach; for example, sacroiliac sub-
luxation and dislocation occur more frequently with the
posterior approach, while infection occurs more frequently following the anterior approach (24). Minor
complications are common and include superficial infections, temporary sensory impairment, and mild or transient pain. Acute and chronic pain at the donor site is
commonly reported, but chronic pain may occur in over
25% of patients who undergo autograft procedures for
spinal fusion (25,26). Although the precise cause of pain
following iliac crest harvest is unknown, such pain is
probably muscular or periosteal in origin and is often
resistant to conventional treatment (26).
Major complications associated with the harvest of tis-
sue from the iliac crest have been reported at rates of
0.7% to 25% (19). These include severe bleeding, herniation, serious infection, scarring, hematoma formation,
injury to nervous or vascular tissue, pelvic fracture, and
chronic pain at the procurement site (20,26–30). Skaggs
et al. reported that after autogenous bone harvest, 15% of
pediatric patients had complications that affected daily
living activities (31).
Skillful surgical technique is essential to avoid injury
to neurologic or vascular tissue during the harvest of iliac
crest bone. Structures that often lie in the dissection path
include the sciatic, iliohypogastric, lateral femoral cutaneous, and cluneal nerves, as well as the superior gluteal
vessels (32) (Fig. 23-2). Damage to nervous and vascular
A
FIG. 23-2. Nervous tissue that can be damaged during harvest of bone from the iliac crest. A: Proximity of anterior incision (dotted line) relative to critical neurologic structures. B: Proximity of posterior incision (dotted line) to cluneal nerves.
B
CHAPTER 23/BIOLOGY OF BONE GRAFTING: AUTOGRAFT AND ALLOGRAFT / 251
tissue has been correlated with the amount of soft tissue
dissected during the procedure (23). The superior gluteal
vessels or the sciatic nerve may be damaged b y dissection
too close to the sciatic notch (33). In addition, chronic
procurement-site pain may result from remo v al of bone in
the sacroiliac region due to disruption of the sacroiliac
joint (32). Since these iatrogenic complications may prolong recovery and increase disability, the surgeon should
be thoroughly familiar with all anatomic structures that
can be damaged during the harvest procedure (32).
Certain conditions require a relatively large amount of
autogenous bone, limiting the applicability of autograft
procedures. For example, obtaining adequate bone stock
for multilevel spinal fusions may not be possible. Conversely, harvesting sufficient autogenous bone may be
impractical in certain patient populations (i.e., older
adults, children, or patients with metastatic carcinoma).
Alternatives to autograft (e.g., allograft or composite
materials) should be considered in these patients as well
as in severely osteopenic patients (30). In patients with
paralytic scoliosis and pelvic obliquity, posterior spinal
fusion typically requires additional instrumentation to the
pelvis, precluding harvest from the posterior ilium
(34,35). An inadequate quantity of autogenous bone in a
graft procedure may result in failure to fuse (36); supplementation of autograft with alternative graft materials
should therefore be considered in cases that may lack sufficient autogenous bone stock.
ALLOGRAFT
Allografts are grafts previously harvested from another
patient, or from the patient undergoing surgery at the
time of surgery. Allografts were originally used only
when the amount of bone-graft material required for a
procedure exceeded the amount of autogenous bone that
could be harvested. Recent improvements in the quality,
safety, and availability of allogeneic materials have
resulted in substantial increases in the use of allograft; in
the mid-1990s, allograft comprised nearly 35% of all
bone grafts performed in the United States (37). The
advantages of allograft include avoidance of donor-site
morbidity , the potential for providing immediate mechanical support, and availability in a variety of forms and
shapes for customized applications. Allograft can be used
as a particulate or structural material. As mentioned, the
histology of bony incorporation differs significantly
between these two preparations.
Although the rate of success for anterior spinal-lumbar
arthrodesis with allograft has been reported to be similar
to that of autograft, the two methods do not produce
equivalent results (38). Allografts can have variability in
bone quality and pose a small, but definite risk of disease
transmission and immunogenic reactions (39). Processing techniques to reduce these risks result in a loss of
osteogenic potential due to the lack of donor cells (40)
and reduced osteoinductive potential (19), presumably
due to the inactivation or removal of osteotropic factors
such as BMPs. The risk of disease transmission is related
to the rigor with which allograft tissue is processed. For
example, transmission of human immunodeficiency virus
(HIV) has been documented in fresh-frozen allograft, but
not in freeze-dried allograft (38,41). T ransmission of HIV
and hepatitis are also dependent on how carefully donors
are screened. For orthopedic applications, freezing,
freeze-drying, and irradiation, sometimes followed by
demineralization, are commonly employed methods for
processing and preserving allograft materials (17,40).
Although freeze-drying reduces immunogenicity and
lengthens shelf life relative to fresh-frozen allograft,
freeze-drying also reduces mechanical strength by up to
50% (19,38,42). In addition, freeze-dried grafts are incorporated into host tissue less completely and retain BMPs
less efficiently than fresh-frozen grafts. In summary,
graft strength, immunogenicity, risk for transmission of
disease, and capacity for incorporation into the host site
can vary widely with the technique used for allograft
preparation. One additional disadvantage of allograft is
its expense.
Demineralized Bone Matrix
Brief mention should be made of demineralized bone
matrix (DBM), a cortical allograft that is further
processed by decalcification, leaving collagen, noncollagenous proteins, and growth factors (43). The resultant
matrix lacks weight-bearing capacity (44) but has
improved osteoinductive potential due to the presence
of low-molecular-weight glycoproteins including BMPs
(45). Decalcification of cortical bone increases the accessibility of these growth factors sequestered within the
bone matrix (1,19,39). In addition, DBM is less immunogenic than conventionally processed allograft (43).
Although DBM has been used clinically with proven success, the osteoinductive potential of DBM can vary,
depending on the method of processing (46). Moreover,
the effectiveness of DBM in promoting new bone formation is also related to the particle size of the matrix and to
the method used for its sterilization (37).
Autograft and Allograft in Combination
As mentioned earlier, allograft may be needed to supplement autograft when the volume of the latter is not
sufficient for a given procedure. Munting et al. used
freeze-dried, cortical allograft for the repair of large,
anterior segmental defects of the spine involving at least
one vertebral body and its two adjacent discs (47). In 41
of 67 cases, autogenous bone, obtained from either the
resected vertebral bodies or the ribs, was used to fill the
medullary cavity. None of the patients experienced infection, transmission of disease, or long-term mechanical
252 /SECTION IV/SURGERY
graft failure over the follo w-up period, which averaged 31
months. Fusion was reported to have been obtained reliably. The authors noted that the use of autograft in the
medullary cavity promoted successful fusion by providing a large surface area for load transmission at the grafthost interface.
Comparison of Auto graft and Allograft
Successful incorporation of bone graft depends on the
quality and quantity of graft material as well as host physiological responses. The graft material requires osteoconductive, osteoinductive, and osteogenic elements in order
for successful new bone growth to occur. Since autogenous bone supplies all three of these items, it is generally
considered superior to that of allograft. Moreover, autograft has produced less variability in clinical results. As
observed by Ehrler and Vaccaro, two primary indications
exist for the use of allograft bone: insufficient autograft
and the requirement for immediate structural support
(38).
In addition to being only weakly osteoinductive and
devoid of osteogenic cells, allograft typically induces an
inflammatory reaction in the host, thus producing an
inflammatory response that may be an important contributor to graft failure (38,48,49). Indeed, allograft may
induce a robust inflammatory reaction immediately after
transplant, resulting in capillary thrombosis, thus further
slowing revascularization and osteoinduction (38). This
leads to tissue necrosis, comprising up to 50% or more of
the graft (38). Animal studies suggest that the host
immune response is specific to donor antigen and consists of killer/suppressor T cells, which are likely mediators of graft rejection (48). The human immune reaction
to allograft bears resemblance to the immune reaction in
animals (50), resulting in a rate of sensitization (67%)
that is higher than that seen after blood transfusion (12%
to 50%) (51). Immunologic factors that mediate rejection
of foreign material share common bone-marrow–derived
precursors and cytokines with the factors responsible for
remodeling of bone; this may help explain the deleterious
interaction between the tw o systems (48). In a study of 29
patients who received allograft, those who lacked sensitization to class II antigens achieved a more satisfactory
clinical outcome compared with patients who exhibited
such sensitization (50). This result provides evidence for
a causal relationship between immunogenicity and less
satisfactory outcome.
The rate of incorporation of graft material is determined by several factors, including anatomic site, size of
the graft area, and size of the graft (12,22). Incorporation
of allograft is qualitatively similar to that of autograft but
occurs at a slow er rate and with more v ariable results. The
variable amount of inflammation arising from allograft
procedures may be largely responsible for these differences. However, the weak osteoinductivity of allograft
may also be a contributing factor to its slower rate of
incorporation relative to autograft. Demineralization of
allograft material improves osteoinductivity. Pals and
Wilkins ha ve reported excellent functional outcomes with
DBM in treating giant bony tumors (52); other authors,
however, have reported variable efficacy in promoting
bone induction (43).
Autograft has been used successfully in posterior cervical, thoracic, and intervertebral fusion procedures (e.g.,
achieving adequate fusion in o ver 90% of patients receiving posterior cervical fusions) (19), but less successfully
in posterolateral lumbar fusion procedures, with some
studies reporting adequate fusion in less than 60% of
such surgeries (19). The success rate for posterolateral
lumbar fusion is even lower when allograft is used alone
or in combination with autograft (38). Success rates for
anterior spinal lumbar fusions with allograft are comparable to autograft (38). High rates of success have also
been reported for allograft posterior lumbar interbody
fusion procedures (38).
Allograft has been shown to be useful as bone-void
filler since it provides early structural support without
donor-site morbidity (50). Perhaps the best indication for
allograft is in adolescent patients undergoing scoliosis
correction and fusion (19). In one study, 40 patients with
idiopathic scoliosis who underwent corrective surgery
were treated with either femoral head allograft or autograft from the iliac crest. Successful unions were obtained
for all patients in both groups. Interestingly, the group
treated with allograft experienced reduced postoperative
pain relative to the group treated with autograft (53).
CONCLUSION
Spinal fusion is a common procedure for treating
trauma, infection, congenital malformations, tumor
growth, or degenerative diseases that threaten bone
integrity. The vast majority of spinal fusion procedures
rely on bone grafting techniques that support bone
remodeling by providing osteogenic potential and, in
some cases, mechanical support. Autogenous cancellous
bone is the “gold standard” for bone graft materials, providing a matrix for osteoconduction, growth factors for
osteoinduction, and osteoprogenitor cells for new bone
formation. Autograft has several disadvantages, however,
including limitations in the quality and quantity of bone
available, and, most significantly, morbidity associated
with the procurement site, usually the iliac crest. Complications of iliac crest harvest can occur in up to 25% of
patients and may lead to prolonged recovery time and
long-term morbidity.
The popularity of allograft has increased over the past
few years due to improved safety, availability, and the
potential for customizing allograft materials to specific
applications. However, allograft has several drawbacks.
Like autograft, allograft exhibits variations in the quality