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464
Z. Buser et al.
in the cortical surface, directed caudally, is made
with an osteotome. Cancellous bone can be
obtained using curettes or gouges. Bone bleeding
is controlled by packing the area with sponges
and applying bone wax or hemostatic agents. The
defect can be filled with allograft.
If a separate incision is required for bone graft
harvesting, a vertical incision is made over the
posterior superior iliac spine (PSIS) with the
patient in the prone position. The alternative
transverse incision, if used, should be made cautiously so as to avoid laceration of the cluneal
nerves. Dissection through the fascia and graft
removal occurs as described above.
To obtain a corticocancellous graft, a longer
exposure is used. The incision for the exposure of
the posterior iliac crest should not exceed 8 cm
from the PSIS to avoid injury to the superior cluneal nerves, which course over the crest. The fascia over the crest is exposed and opened. The
musculature is elevated using subperiosteal technique. The dissection should not extend too inferiorly to avoid jeopardizing the structures in the
region of the sciatic notch.
The subcrestal approach is an alternative
method for obtaining bicortical and cancellous
graft. An incision 1 cm lateral to the PSIS allows
exposure as described above. Instead of simply
perforating the surface of the cortex, however, a
unicortical window can be cut with osteotomes
or a saw. Additional cancellous bone can then be
harvested through the same opening. Care should
be exerted during closure of the fascial layer to
avoid damage to the gluteal musculature. With
meticulous hemostasis, a postoperative drain is
unnecessary.
10% in her neck. She has had these symptoms for
approximately 6 months.
Conservative Treatments
She has had physical therapy which was of no
significant help. She underwent two epidural steroid injections; the first was at C5-C6 which gave
her complete relief of shoulder blade pain for
2 days. The second was at C7-T1 and it helped
the burning in her arms for approximately a
week.
Physical Exam
Her exam is normal except for diminished sensation in the bilateral C7 and T1 distributions.
Imaging
Preoperative lateral radiograph shows multilevel
spondylosis with disc space collapse from C5 to
T1 (Fig. 34.2). MRI confirms spinal stenosis due
to broad- based disc bulges from C5 to T1
(Fig. 34.3). There is disc extrusion at C7-T1 with
caudal migration also noted.
Illustrative Case
History
Patient is 59-year-old, right-hand dominant
female with a history of bilateral shoulder blade
pain, worse on the left. She also has complaints
of burning in the bilateral T1 distribution. She
states that the pain is 80% in her shoulder blades,
10% down her arms in the T1 distribution, and
Fig. 34.2 Preoperative lateral radiograph shows multilevel spondylosis with disc space collapse from C5 to T1
34 Bone Grafting and Spinal Fusion Options
465
Fig. 34.3 Pre-op MRI shows stenosis due to broad-based
disc bulges from C7 to T1. There is disc extrusion at
C7-T1 with caudal migration also noted
Surgical Treatment
Due to the severity of her symptoms and failure
of conservative management, the patient opted
for surgical intervention. The planned procedure
was a C5-T1 anterior cervical discectomy and
fusion with harvesting of iliac crest autograft.
The autograft was harvested through a small incision, and the cancellous bone was packed into
PEEK interbody cages (Figs. 34.4 and 34.5).
Outcome
She had immediate improvement in pain and
gradual improvement in hand sensation. Her
fusion progressed and appeared healed on 6- and
12-month radio-graphs (Figs. 34.6 and 34.7).
Technical Pearls
Fig. 34.4 Two-week postoperative radiograph showing
cancellous bone within the PEEK interbody cages
Fig. 34.5 At 6 weeks postoperative radiograph showed
early maturation of the autograft
• Autologous bone graft (commonly harvested
from the iliac crest) is the only graft that has
all the three characteristics needed for bone
formation: osteoconduction, osteoinduction,
and osteogenicity.
• Bone grafts can function as graft substitutes,
graft extenders, or graft enhancers.
• Allograft materials can be fresh, fresh frozen,
or freeze-dried depending on the harvest and
preparation.
466
Fig. 34.6 Six-month postoperative radiograph showing
continue maturation of graft
Z. Buser et al.
• Irrigate before decorticating so you leave all
bone dust and fragments in the area to promote bone healing. No need to wash away
those small graft particles.
• Decorticate only the dorsal cortex off the
structure. Expose the cancellous bone which
promotes bone attachment. No need to decorticate the good cancellous bone away. Don’t
over-decorticate this cancellous bone which
you want to leave in place.
• Expose as much of this cancellous bone as
you can. Decorticate the cortical bone as much
as possible to create as much surface area for
new bone to heal. Expose not just the transverse processes but the facet joints and as
much surface area as possible.
• Place the bone graft as much as you can on top
of the decorticated bone. Don’t leave it suspended in the paraspinal muscles, but instead
put the graft right on top of where the bone
needs to attach. Don’t make it harder for the
bone to bridge the gap.
• Remove soft tissues from local bone graft.
The soft tissues attached to the graft particles
will inhibit bone formation.
• Put your best material right on decorticated
graft bed.
• Be very careful to examine the evidence supporting the efficacy of the particular product
you are considering. Often the supporting evidence is poor, or it has in vitro data that does
not convey any real significant support for
efficacy.
Fig. 34.7 One-year postoperative radiograph showing
solid interbody fusion from C5 to T1
• Ceramics are easily obtainable in large
amounts with appropriate pore size for cell
and blood vessel ingrowth; however, they lack
mechanical stability.
• Bone marrow aspirates contain cells and
growth factors, but the quality varies with
donor age and medical history.
Conclusion
A wide array of bone grafting materials has been
used in spinal fusions in combination with autograft or as a graft substitute. Despite the existing
literature on each of those graft substitutes, a
strong level of preclinical and clinical research is
missing. Understanding the biology of each bone
allograft is critical for achieving successful spinal fusion. One must be cautious when choosing
the grafting material and consider all factors such
as patient’s age, comorbidities, surgery type, and
number of levels.
34 Bone Grafting and Spinal Fusion Options
467
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Basic Science of Bone Fusion
Joseph A. Weiner and Wellington K. Hsu
35
Introduction
Bone regeneration is critical for many orthopedic
procedures such as fracture repair, osteotomies,
and spine fusion. Understanding the molecular
and cellular mediators of bone healing is essential for the treating surgeon who must ensure that
the critical components of bone repair are present
during surgery. Spine arthrodesis is frequently
performed in the treatment of spine trauma,
deformity, and complex degenerative disorders.
With an estimated 413,000 fusion procedures
performed in the United States annually, the
number of procedures performed has increased
by 2.4-fold since 1998 [1]. The success of spine
surgery in these conditions depends on the reestablishment of spinal stability. While spinal
instrumentation may afford temporary support, a
bony union must be formed to provide enduring
stability.
Failure of fusion, or pseudarthrosis, is associated with poor long-term clinical outcomes
and an increase in the 10-year reoperation rate
2, 3]. Recently, pseudarthrosis rates for lum-
[
bar spine fusions have been reported from 5%
to 48% [4–6] with a higher incidence in
fusions spanning three or more spinal levels
[7]. The rate of nonunion following anterior
cervical discectomy and fusion (ACDF) can
vary depending on the number of levels fused,
the allograft type used, and the surgical technique; however, it is frequently reported to be
between 0% and 20% in single- level ACDF to
over 60% in multilevel fusions [8]. Given the
rising number of spine fusions performed, it is
essential that surgeons be aware of the pathophysiologic processes that can lead to this
complication. This chapter will review the
basic biological and physiological principles
of bone healing in an effort to assist the spine
surgeon in selecting the most efficacious techniques for achieving successful arthrodesis.
Furthermore, we will briefly discuss promising areas of research in the treatment and prevention of pseudarthrosis.
Basic Science of Bone
Bone Anatomy and Histology
J.A. Weiner, MD (*) • W.K. Hsu, MD
Department of Orthopaedic Surgery, Northwestern
University Feinberg School of Medicine,
676 N. St. Clair St., #1350, Chicago, IL 60611, USA
e-mail: Joseph.Weiner@northwestern.edu;
Whsu@nm.org
© Springer International Publishing AG 2017
L.T. Holly, P.A. Anderson (eds.), Essentials of Spinal Stabilization,
DOI 10.1007/978-3-319-59713-3_35
Bone is a dynamic biological tissue comprised
of metabolically active cells incorporated into a
rigid mineralized matrix framework. An understanding of the relationship between the anatomic structure and histology of bone tissue is
471
472
J.A. Weiner and W.K . Hsu
critical to understand the process of bone healing and fusion. On a cellular level, bone consists
of four main cell types: osteogenic precursor
cells (stem cells), osteoblasts, osteoclasts, and
osteocytes [9–11]. Contained within the marrow
space are numerous other cells types critical for
hematopoiesis. Osteogenic progenitor cells, a
derivative of mesenchymal stem cells, serve as
the cellular reserve of bone tissue. They are
present within the inner layer of the periosteum
which envelops the outer surface of bone and on
the endosteum that lines the medullary surface
of compact bone. Similarly, these osteogenic
progenitor cells are also found within the endosteum lining the surface of trabecular bone within
vertebrae.
Osteoblasts, derived from osteogenic precursor cells, are mature bone-forming cells.
They secrete osteoid that subsequently undergoes mineralization, providing strength and
rigidity. As osteoblasts lay down osteoid, cells
become incorporated into the matrix and
become osteocytes, while others remain on
resorptive surfaces to participate in bone turnover alongside osteoclasts. From each osteocyte a web of cytoplasmic processes extends
through canaliculi to blood vessels and other
osteocytes, forming a critical network that
allows bone to function as a living tissue.
Osteocytes are involved in the control of the
extracellular concentration of calcium and
phosphorus, as well as in adaptive remodeling
behavior via cell-to-cell interactions in response
to the local environment [12–14].
Osteoclasts, derived from macrophages,
are multinucleated, bone-resorbing cells
controlled by hormonal and cellular mechanisms. These cells function in cutting cones
and dissolve the inorganic and organic matrices of bone and calcified cartilage via the
release of catabolic enzymes. This process
results in the formation of shallow erosive
pits on the bone surface called Howship’s
lacunae. The delicate balance between osteoblast and osteoclast activity mediates the
metabolic turnover of bone. When these processes are disrupted, conditions such as
Paget’s disease are seen.
Bone Metabolism
Bone metabolism is under continual regulation
by a multitude of hormonal factors and local
mediators, many of which play a critical role in
bone healing during spine fusion. Three of the
hormones that play a crucial role in calciumphosphate homeostasis and bone metabolism are
parathyroid hormone (PTH), vitamin D, and calcitonin. PTH increases free serum calcium and
maintains the body’s extracellular calcium levels
at a relatively constant level [
while PTH is typically considered to be a bone
catabolic agent, when delivered intermittently at
low doses, PTH potently stimulates cortical and
trabecular bone growth by increasing osteoblast
proliferation and differentiation, decreasing
osteoblast apoptosis and reducing the inhibitory
effects of peroxisome proliferator activator
(PPAR)γ receptor on osteoblast differentiation
[15].
Calcitonin, a peptide hormone secreted by the
parafollicular cells of the thyroid gland, serves to
counteract the activities of PTH. Rising serum
calcium levels cause calcitonin to be released in
an attempt to return calcium levels to a homeostatic level. More specifically, calcitonin lowers
blood calcium levels through four mechanisms:
inhibiting calcium absorption by the intestines,
inhibiting osteoclast activity, stimulating osteoblast activity, and inhibiting renal tubular cell
reabsorption of calcium allowing excretion in the
urine [18, 19].
With the finding of the vitamin D receptor
(VDR) in nearly all tissues and the recent discovery of thousands of VDR binding sites throughout the genome, the interest in vitamin D and its
impact on multiple biologic processes has accelerated tremendously [20, 21]. In the arena of
bone metabolism, vitamin D’s role is well established. Vitamin D stimulates intestinal and renal
calcium-binding proteins and facilitates active
calcium transport [22]. Vitamin D is also critical
to the process of osteoid mineralization [21].
Together, the interplay between vitamin D, PTH,
and calcitonin helps to maintain bone homeostasis, a process critical to osteoid mineralization
and normal bone healing following surgery.
15–17]. Interestingly,
35 Basic Science of Bone Fusion
473
Principles of Bone Healing
While understanding bone metabolism is critical,
it does not fully explain the process of bone healing after a fracture or following fusion surgery.
Bone healing is dependent on four elements: an
osteoinductive stimulus, an osteoconductive
matrix, a source of osteogenic cells, and a viable
vascular supply (Fig.
ronment is also vital, as bone is remodeled in
response to load (Wolff’s law). If any of these
crucial factors is absent, new bone formation is
significantly diminished [23, 24].
Osteoinduction is the process of recruitment
of immature osteogenic precursor cells and subsequent stimulation to differentiate into osteoblasts. This process requires a stimulus to trigger
differentiation of precursor cells into mature
osteoblasts; often this stimulus comes in the form
of local growth factors released from platelets,
macrophages, and fibroblasts in response to bone
injury [25, 26]. Examples of important growth
factor mediators include bone morphogenetic
peptides, fibroblast growth factor (FGF), insulinlike growth factor (IGF), platelet-derived growth
factor (PDGF), and transforming growth factor-β
(TGF-β). The most widely studied growth factors
are those in the bone morphogenetic protein
(BMP) family. BMPs are soluble cytokines of the
transforming growth factor beta superfamily
involved in the differentiation, maturation, and
proliferation of mesenchymal precursor cells into
osteogenic cells. To date, over 20 types have been
35.1). The mechanical envi-
described and are typically present in only minute quantities in the body. However, two commercial forms of recombinant BMP are available
for clinical use: rhBMP-2 (INFUSE) (Medtronic –
Memphis, TN) and rhBMP-7 (OP-1) (Olympus
Biotech Corporation – Hopkinton, MA) [27].
BMPs act via serine-threonine kinase receptors
found on the surface of target cells and transduce
their signal via the SMAD pathway, leading to
nuclear translocation and subsequent expression
of target genes involved in osteogenesis [28, 29].
Osteoconduction is the physical property of
the matrix or graft to serve as a scaffold for viable
bone healing. Physiologically, osteoid deposition
by osteoblasts serves as an initial osteoconductive scaffold during fracture healing.
Osteoconduction allows for neovasculaturization
and the infiltration of osteogenic precursor cells
into the fusion or healing site. In the context of
spine fusion, numerous graft materials such as
cancellous autografts and allografts, demineralized bone matrix, ceramics, and collagen sponges
can serve as osteoconductive scaffolds for new
bone growth to occur [7, 30, 31]. Scaffold properties such as compressive strength, biocompatibility, and pore size determine its ability to
successfully aid bone regeneration [31, 32].
Osteogenesis refers to the process of creating
new bone and typically denotes the presence of
viable mesenchymal stem cells, osteoblasts, and
osteocytes in a graft material [31]. During the
early stages of bone healing, these cell types are
essential to new bone formation and bony union.
Fig. 35.1 Key elements
of bone healing. Bone
healing requires
interplay between four
factors: an
osteoinductive stimulus,
an osteoconductive
matrix, a source of
osteogenic cells, and a
viable vascular supply