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78
5
Physiology of Bone Grafts and
Bone Graft Substitutes
General Considerations
I. Process of bone formation
A. Osteogenesis: mesenchymal cell differentiation into osteoblasts
B. Osteoinduction: induction of bone formation via a growth factor
C. Osteoconduction: creeping bone substitution through a lattice structure
II. Autograft and allograft incorporation
A. Physiology of bone graft incorporation
1. Recruitment of undifferentiated progenitor cells from host bed and
autograft
2. Chemotaxis of these progenitor cells is induced by release of intracel-
lular products from
a. Cell death
b. Surgical trauma
c. Decortication
d. Low oxygen tension and low pH
3. Osteogenic cells from autograft may directly form bone
a. Undifferentiated progenitor cells become chondroblasts and os-
teoblasts mediated by chemical factors (osteoinduction).
(1) Prostaglandins
(2) Growth factors (Transforming Growth Factor [TGF], Fibroblast
Growth Factor (FGF), Platelet Derived Growth Factor (PDGF), In-
sulin-like Growth Factor (IGF))
(3) Bone Morphogenetic Protein (BMP–2, BMP–7)
4. Bony incorporation or osteoconduction
a. A scaffold is established on which new bone is produced.
b. Vascular and cellular ingrowth
◆
Chapter 5 Physiology of Bone Grafts and Bone Graft Substitutes 79
B. Autograft
1. Osteogenic, osteoinductive, and osteoconductive
2. No disease transmission
3. No immune reaction
4. Donor site morbidity
5. Limited supply
6. Types
a. Cortical
b. Corticocancellous
c. Cancellous
d. Vascularized
C. Allograft
1. Osteoconductive and weakly osteoinductive
2. Possible disease transmission and immune reaction
3. Slower incorporation
4. Higher infection rate
5. Available in multiple forms
6. No graft site morbidity
III. Factors affecting spinal fusion
A. Patient factors
1. A ge
2. Smoking
3. Diabetes mellitus
4. Metabolic bone disease
B. Anatomic regions
1. Cervical, thoracic, lumbar
2. Anterior versus posterior
C. Surgical procedures
1. First or revision surgery
2. Levels of fusion
3. Instrumentation
4. Surgical techniques
a. Meticulous decortication
b. Graft preparation
D. Types and quantity of bone graft
E. Postoperative orthosis
F. Medications
1. Nonsteroidal antiinflammatory drugs
2. Chemotherapy
G. Radiation
H. Electrical stimulation
I. Ultrasound
J. Spinal alignment
IV. General categories of bone grafts compounds
A. Substitutes—intended to replace autograft
80 I Patient Evaluation and Spine Overview
B. Extenders—used in combination with autograft to increase the amount of
osteoconductive and osteoinductive factors for fusion
C. Enhancers—growth factors used in conjunction to increase the rate of
fusion. Cannot be used alone.
V. Posterior spinal fusion
A. Requirements for successful fusion
1. Stability
a. Rigid instrumentation required
2. Osteogenesis
3. Osteoinductivity
4. Osteoconductivity
5. Allograft versus autograft
a. Autograft superior to allograft in the adult
b. Allograft acceptable in pediatric thoracolumbar fusion cases but
autograft is still superior.
c. Slower healing expected with allograft
d. Allograft alone is not acceptable in posterior cervical in any age group.
e. A high incidence of allograft resorption in adult posterolateral
fusions even with rigid instrumentation
f. Allograft may be used as a graft extender.
g. Demineralized bone matrix, calcium phosphate, or calcium sulfate
ceramics may be used as graft extenders or graft expanders.
VI. Anterior spinal fusion
A. Requires stability and osteoconductivity for successful fusion
B. Stability is the most important factor for fusion.
1. More important than osteoinductivity and osteoconductivity
2. Structural grafts should be biologically compatible and biomechani-
cally stable.
3. Porosity and osteoinductivity can enhance healing and graft incorporation.
C. Anterior cervical fusion
1. Autograft superior to allograft in fusion rates and minimizing graft col-
lapse
2. Allograft strut grafts are acceptable for one–level instrumented cases.
a. Pseudarthrosis higher in multilevel cases
b. Plating may decrease the incidence of pseudarthrosis.
c. Strut grafts
d. Tricortical iliac crest graft is the gold standard.
(1) Fibula may be used for long constructs.
(2) Combination of titanium cage plus autograft is effective.
D. Anterior thoracolumbar fusion
1. Stability is the key to graft incorporation.
2. Strut allograft plus autogenous cancellous graft is as effective as a strut
autograft.
a. Tricortical iliac crest is the gold standard.
b. Allografts (fibula) is slow to incorporate.
(1) Ribs are used as augmentation.
Chapter 5 Physiology of Bone Grafts and Bone Graft Substitutes 81
(2) Vascularized rib may enhance graft incorporation.
(3) Titanium cage plus autogenous cancellous graft is effective.
(4) Femoral rings with autogenous cancellous bone
(5) Harms cages with cancellous bone
VII. Experimental bone graft substitutes
A. Bone marrow and osteoprogenitor cells
1. The number of stem cells in the bone marrow
a. One in 50,000 in young individual
b. One in 2,000,000 in the elderly
c. Autogenous bone contains osteoblastic cells.
B. Tissue engineering to increase the fusion rate
1. Osteoconductive materials
a. Carriers (demineralized bone matrix [DBM], collagen, polymers,
ceramic) versus structural replacement (ceramic, carbon fiber,
tantalum)
(1) DBM
(a) Acid extraction of bone leaves behind growth factors and
proteins.
(b) Removes the mineral content
(c) Urist reported DBM inducing bone formation in 1965.
(d) A variety of DBM products
(i) Grafton
TM
gel, putty, sheet (Osteotech, Inc., Eaton
town, NJ)
(ii) Dynagraft
TM
with pleuronic reverse–phase copolymer
carrier firms with body temperature (GenSci Regener-
ation Science, Inc., Vancouver, BC, Canada)
(iii) Osteofil
TM
thermoplastic, collagen–based, hydrogel
carrier matrix (Regeneration Technologies Inc.,
Alachua, FL)
(iv) Allomatrix
TM
calcium sulfate pellets (Wright Medical
Technologies, Arlington, TN)
(2) Ceramics
(a) Biomechanical strength
(i) Low fracture resistance and tensile strength
(ii) Questionable indication for anterior grafting without
supplemental fixation
(b) Bonding and release of BMPs
(c) Calcium–based ceramics
(i) Hydroxyapatite, tricalcium–phosphate
(ii) Calcium sulfate
(iii) Calcium phosphate cements
(iv) Calcium phosphate ceramics
(d) Commercially available products
(i) ProOsteon (EBI, Porsipphny, NJ)
(ii) Osteoset (Wright Medical, Arlington, TN)
(iii) Collagraft (Zimmer, Warsaw, IN)
(iv) Bone Source (Stryker, Kalamazoo, MI)
82 I Patient Evaluation and Spine Overview
(v) Healos (Depuy Spine) Raynom, MA
(vi) Vitoss (OrthoVita) Malvern, PA
(e) Clinical use of ceramics
(i) Anterior spinal application
* Combination with cages or plates
(*) Yamamuro et al, 1988, 1990 (bioactive non-
porous ceramics)
(**) Matsui et al, 1994 (alumina ceramic spacers)
(***) Thalgott et al, 1995 (coralline porous hydroxy
apatite ceramic with anterior plate)
(ii) Filling bony defects (vertebroplasty/kyphoplasty)
(iii) Posterior application
* Requires addition of osteoinductive material (graft
extender, carrier of BMPs)
2. Osteoinductive growth factors
a. Purified and concentrated proteins or recombinant human growth
factors have shown safety and efficacy in promoting bone forma-
tion and spinal fusion in a variety of animal experiments.
(1) BMPs
(2) TGF–
(3) Human clinical trials are ongoing.
b. Autologous growth factor
(1) Blood spun down to concentrate growth factors such as PDGF,
TGF–b
(2) Limited basic science and clinical studies
Suggested Reading
An HS, Simpson JM, Glover JM, Stephany J. Comparison between allograft plus demineralized bone ma-
trix vs. autograft in anterior cervical fusion. A prospective randomized multi–center study. Spine
1995;20:2211-2216
Boden SD, Martin GJ Jr, Maronl M, et al. The use of coralline hydroxyapatite with bone marrow, autoge-
nous bone graft, or osteoinductive bone protein extract for posterolateral lumbar spine fusion. Spine
1999;24: 320-327
Boden SD, Schimandle JH, Hutton WC: 1995 Volvo Award in basic sciences. The use of an osteoinductive
growth factor for lumbar spine fusion. Spine 1995;20:2633-2644
Geisler FH. Bone graft extenders. J Neurosurg Spine 2005;3:332-333
Grauer JN, Beiner JM, Kwon B, et al. The evolution of allograft bone for spinal applications. Orthopedics
2005;28:573-7; quiz 8-9.
Helm GA. Bone graft substitutes for use in spinal fusions. Clin Neurosurg 2005;52:250-255
Kwon B, Jenis LG. Carrier materials for spinal fusion. Spine J 2005;5:224S-230S
Sandhu HS, Kanim LEA, Kabo JM, et al. Effective doses of recombinant human bone morphogenetic pro-
tein–2 in experimental spinal fusion. Spine 1996;21:2115-2122
Zdeblick TA, Cooke ME, Kunz DN, Wilson D, McCabe RP. Anterior cervical discectomy and fusion using a
porous hydroxyapatite bone graft substitute. Spine 1994;19:2348-2357
II
Trauma
6 Evaluation and Management of Spinal Cord Injury
7 Spinal Rehabilitation and Disability Evaluation
8 Cervical Spine Trauma
9 Thoracolumbar Spine Fractures
85
6
Evaluation and Management
of Spinal Cord Injury
I. Introduction
A. Approximately 12,000 to 14,000 spinal cord injuries occur in North America
per year.
1. Most commonly affect adolescent males
2. Most are caused by motor vehicle collisions
II. Prehospital evaluation period
A. Care of any trauma patient begins with immobilization of the spine at the
scene of injury.
B. American College of Surgeons mnemonic for in-field management of a
trauma patient
1. A—airway
2. B—breathing
3. C—circulation
4. D—disability
5. E—exposure and environment
C. All trauma patients should be immobilized with a rigid cervical orthosis
and transferred using lateral bolsters.
1. The patient should be placed on a long backboard secured with tapes
or straps.
2. Helmeted athletes
a. Helmet and shoulder pads should not be removed.
III. Emergency room management
A. Polytrauma patients may have an altered level of consciousness and are
vulnerable to further worsening of their neurological injuries.
B. Once the ABC’s have been established, a thorough but focused physical ex-
amination to assess the patient’s neurological function should be performed.
1. Entire spinal column should be palpated for “step-off” or misalign-
ment of the spinous processes.
86 II Trauma
C. Head trauma
1. Glasgow coma scale
a. Total score can range from 15 (normal responses to stimuli) to 3 (no
response or comatose) (Table 6–1).
D. Evaluation of airway and breathing
1. Elective intubation should be performed in patients with severe head
injuries or who are unable to protect the airway because of a de-
pressed level of consciousness (Glasgow coma scale 8).
2. Patients with spinal cord injuries (particularly above C5) having diffi-
culty with respiration should be considered for elective intubation.
3. Manual in-line stabilization of the cervical spine during orotracheal in-
tubation is a technique that minimizes motion of the unstable cervical
spine.
E. Neurological examination
1. American Spinal Injury Association (ASIA) standard of neurological
testing provides a concise and detailed method of evaluating spinal
cord and peripheral nerve root function.
a. Sensation is determined in all 28 dermatomes bilaterally by the pa-
tient’s ability to detect the sharp end of a pin (Fig. 6–1).
b. Motor function is documented and graded 1 to 5 based on resist-
ance to physical manipulation or gravity (Table 6–1).
c. Based on both the motor and sensory examination, the patient is
further classified or graded using the ASIA modification of the
Frankel neurological classification system (Table 6–2).
F. Spinal cord injuries
1. Complete injury
a. No functional motor (less than grade III motor strength) or sensory
activity below the zone of injury
2. Incomplete injury
Table 6-1 Glasgow Coma Scale
Eye opening Voice 3
Pain 2
None 1
Verbal response Oriented 4
Inappropriate 3
Incomprehensible 2
None 1
Motor response Obeys commands 5
Localized pain 4
Withdraws 3
Decorticate 2
Decerebrate 1
Figure 6-1 ASIA spinal cord injury assessment form. From the American Spinal Injury Association. International Standards for Neurological Classification of
Spinal Cord Injury, revised, 2002. (Chicago, IL. American Spinal Injury Association; 2006. Reproduced with permission.)