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 intracellular 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 osteoblasts mediated by chemical factors (osteoinduction).

(1) Prostaglandins

(2) Growth factors (Transforming Growth Factor [TGF]β, Fibroblast Growth Factor (FGF), Platelet Derived Growth Factor (PDGF), Insulin-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

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. Age

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

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 biomechanically 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 collapse

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.

(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™ gel, putty, sheet (Osteotech, Inc., Eaton town, NJ)

(ii) Dynagraft™ with pleuronic reverse–phase copolymer carrier firms with body temperature (GenSci Regeneration Science, Inc., Vancouver, BC, Canada)

(iii) Osteofil™ thermoplastic, collagen–based, hydrogel carrier matrix (Regeneration Technologies Inc., Alachua, FL)

(iv) Allomatrix™ 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)

(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 formation and spinal fusion in a variety of animal experiments.

(1) BMPs

(2) TGF–β

(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

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