Bone grafting

• Bone grafting ( Table 1.10)

  • Graft properties

    • Osteoconductive matrix: acts as a scaffold or framework for bone growth

    • Osteoinductive factors: growth factors (BMP) that stimulate bone formation

    • Osteogenic cells: primitive mesenchymal cells, osteoblasts, and osteocytes

    • Structural integrity

  • Specific bone graft types

    • Cortical bone graft

      • Slower incorporation: remodels existing haversian systems through resorption (weakens the graft) and then deposits new bone (restores strength)

      • Resorption confined to osteon borders; interstitial lamellae are preserved.

      • Used for structural defects

      • Insufficiency fracture eventually occurs in 25% of massive grafts.

    • Cancellous graft

      • Useful for grafting nonunion and cavitary defects

      • Revascularizes and incorporates quickly

Osteoblasts lay down new bone on old trabeculae, which are later remodeled (“creeping substitution”).

 

 

Table 1.7

 

Biochemical Steps of Fracture Healing

 

 

Step	Collagen Type
Mesenchymal	I, II, III, V
Chondroid	II, IX
Chondroid-osteoid	I, II, X
Osteogenic	I

 

 

 

Table 1.8

 

Growth Factors of Bone

 

 

Growth Factor Action Notes
Bone morphogenetic protein	Osteoinductive; stimulates bone formation Induces metaplasia of mesenchymal cells into osteoblasts	Target cells of BMP are the undifferentiated perivascular mesenchymal cells; signals through serine-threonine kinase receptors Intracellular molecules called SMADs serve as signaling mediators for BMPs
Transforming growth factor–β	Induces mesenchymal cells to produce type II collagen and proteoglycans Induces osteoblasts to synthesize collagen	Found in fracture hematomas; believed to regulate cartilage and bone formation in fracture callus; signals through serine/threonine kinase receptors Coating porous implants with TGF-β enhances bone ingrowth
IGF-2	Stimulates type I collagen, cellular proliferation, cartilage matrix synthesis, and bone formation	Signals through tyrosine kinase receptors
Platelet-derived growth factor	Attracts inflammatory cells to the fracture site (chemotactic)	Released from platelets; signals through tyrosine kinase receptors

• Vascularized bone graft

  • Although technically difficult to implant, allows more rapid union and cell preservation; best for irradiated tissues or large tissue defects (morbidity may occur at donor site [e.g., fibula])

  • Nonvascular bone grafts are more common

• Allograft bone

  • Types

    • Fresh: increased immunogenicity

    • Fresh frozen: less immunogenic than fresh; BMP preserved

    • Freeze dried (lyophilized “croutons”): loses structural integrity and depletes BMP, is least immunogenic, is purely osteoconductive, has lowest risk of viral transmission

    • Bone matrix gelatin (a digested source of BMP): demineralized bone matrix is osteoconductive and osteoinductive.

    • Osteoarticular (osteochondral) allograft

       

  • Antigenicity

• Immunogenic (cartilage is vulnerable to inflammatory mediators of immune response)

• Articular cartilage preserved with glycerol or DMSO

• Cryogenically preserved grafts (leave few viable chondrocytes)

• Tissue-matched (syngeneic) osteochondral grafts (produce minimal immunogenic effects and incorporate well)

  • Allograft bone possesses a spectrum of potential antigens, primarily from cell surface glycoproteins.

Classes I and II cellular antigens in allograft are recognized by T

lymphocytes in the host.

 

 

Table 1.9

 

Endocrine Effects on Fracture Healing

 

 

Hormone Effect Mechanism
Cortisone	–	Decreased callus proliferation
Calcitonin	+?	Unknown
Thyroid hormone, PTH	+	Bone remodeling
Growth hormone	+	Increased callus volume

• Primary mechanism of rejection is cellular rather than humoral.

• Incorporation related to cellularity and MHC incompatibility.

• Cellular components that contribute to antigenicity are marrow origin, endothelium, and retinacular activating cells.

  • Marrow cells incite the greatest immunogenic response.

• Extracellular matrix components that contribute to antigenicity are as follows:

  • Type I collagen (organic matrix): stimulates cell-mediated and humoral responses

  • Noncollagenous matrix (proteoglycans, osteopontin, osteocalcin, other glycoproteins)

• Hydroxyapatite does not elicit immune response.

• Demineralized bone matrix

  • Acidic extraction of bone matrix from allograft

  • Osteoconductive without structural support

  • Minimally osteoinductive despite preservation of

    osteoinductive molecules

• Synthetic bone grafts: calcium, silicon, or aluminum

  • Calcium phosphate–based grafts: capable of osseoconduction and osseointegration

    • Biodegrade very slowly

    • Highest compressive strength of any graft material

    • Many prepared as ceramics (heated apatite crystals fused into crystals [sintered])

  • Tricalcium phosphate

  • Hydroxyapatite; purified bovine dermal fibrillar collagen plus ceramic hydroxyapatite granules and tricalcium phosphate granules

  • Calcium sulfate: osteoconductive

    • Rapidly resorbed

  • Calcium carbonate (chemically unaltered marine coral): resorbed and replaced by bone (osteoconductive)

  • Coralline hydroxyapatite: calcium carbonate skeleton is converted to calcium phosphate through a thermoexchange process.

Silicate-based: incorporate silicon as silicate (silicon dioxide); bioactive glasses and glass-ionomer cement

 

Table 1.10

 

 

Types of Bone Grafts and Bone Graft Properties

 

 

Properties Graft Osteogenic Struc Osteoconduction Osteoinduction Cells Integ
Autograft
Cancellous	Excellent	Good	Excellent	Poor
Cortical	Fair	Fair	Fair	Exce
Allograft	Fair	Fair	None	Good
Ceramics	Fair	None	None	Fair
Demineralized bone matrix	Good	Fair	None	Poor
Bone marrow	Poor	Poor	Good	Poor

 

 

Modified from Brinker MR, Miller MD: Fundamentals of orthopaedics,

Philadelphia, 1999, Saunders, p 7.

 

• Aluminum oxide: alumina ceramic bonds to bone in response to stress and strain between implant and bone

• Five stages of graft healing (Urist) are listed in Table 1.11.

• Distraction osteogenesis

  • Definition: distraction-stimulated formation of bone

  • Clinical applications:

    • Limb lengthening

    • Deformity correction (via differential lengthening)

    • Segmental bone loss (via bone transport)

  • Biologic features:

    • Under optimal stability, intramembranous ossification occurs.

    • Under instability, bone forms through enchondral ossification.

      • Under extreme instability, pseudarthrosis may occur.

  • Three histologic phases:

    • Latency phase (5–7 days)

    • Distraction phase (1 mm/day [≈1 inch/mo])

    • Consolidation phase (typically twice as long as distraction phase)

  • Optimal conditions during distraction osteogenesis:

    • Low-energy corticotomy/osteotomy

    • Minimal soft tissue stripping at corticotomy site (preserves blood supply)

    • Stable external fixation and elimination of torsion, shear, and bending moments

    • Latency period (no lengthening) 5–7 days

    • Distraction: 0.25 mm three or four times per day (0.75–1.0 mm/day)

    • Neutral fixation interval (no distraction) during consolidation

    • Normal physiologic use of the extremity, including weight bearing

• Heterotopic ossification

  • Ectopic bone forms in soft tissues.

    • Most commonly in response to injury or surgical dissection

    • Myositis ossificans: heterotopic ossification in muscle

  • Increased risk with traumatic brain injury

    • Recurrence after resection is likely if neurologic compromise is severe.

    • Timing of surgery for heterotopic ossification after traumatic brain injury is important:

      • Time since injury (3–6 months)

      • Evidence of bone maturation on radiographs (sharp demarcation, trabecular pattern)

  • Heterotopic ossification may be resected after total hip arthroplasty (THA).

    • Resection should be delayed for 6 months or longer after THA.

Adjuvant radiation therapy may prevent recurrence of heterotopic ossification.

 

 

Table 1.11

 

Stages of Graft Healing

 

 

Stage Activity
Inflammation	Chemotaxis stimulated by necrotic debris
Osteoblast differentiation	From precursors
Osteoinduction	Osteoblast and osteoclast function
Osteoconduction	New bone forming over scaffold
Remodeling	Process continues for years

• Optimal therapy: single preoperative or postoperative dose of 600–800 rad/cGy (6-8 Gy)

• Prevents proliferation and differentiation of primordial mesenchymal cells into osteoprogenitor cells

• Preoperative radiation (600–800 rad/cGy) may be given in a single fraction up to 24 hours prior to surgery.