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Updated: Apr 4 2022

Bone Grafting

4.2

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  • Introduction
    • A material with either osteoconductive, osteoinductive, and/or osteogenic properties
      • autografts
      • allografts
      • demineralized bone matrix (DBM)
      • synthetics
      • bone morphogenetic protein (BMP)
      • stem cells
    • Epidemiology
      • incidence
        • almost 1 million bone grafting procedures performed in US each year, with a growth of almost 13% per year
    • Indications
      • assist in healing of fractures, delayed unions, or nonunions
      • assist in arthrodeses and spinal fusions
      • replace bone defects from trauma or tumor
    • Resorption rates
      • relative resorption rates of bone graft substitutes
        • fastest to slowest
          • calcium sulfate > tricalcium phosphate > hydroxyapatite
    • Outcomes
      • allograft retrieval
        • retrieval studies are helpful in understanding the body's response to allografts
        • 5 years after implantation, allograft articular cartilage is completely acellular - no donor or recipient chondrocytes will be present
  • Properties
    • Bone graft has aspects of one or more of these three properties
      • osteoconductive
        • material acts as a structural framework for bone growth
          • demineralized bone matrices (DBMs)
        • the various three-dimensional makeups of the material dictate the conductive properties
      • osteoinductive
        • material contains factors that stimulate bone growth and induction of stem cells down a bone-forming lineage
          • bone morphogenetic protein (BMP) is most common from the transforming growth factor beta (TGF-B) superfamily
      • osteogenic
        • material directly provides cells that will produce bone including primitive mesenchymal stem cells, osteoblasts, and osteocytes
          • mesenchymal stem cells can potentially differentiate down any cell line
          • osteoprogenitor cells differentiate to osteoblasts and then osteocytes
        • cancellous bone has a greater ability than cortical bone to form new bone due to its larger surface area
        • autologous bone graft (fresh autograft and bone marrow aspirate) is the only bone graft material that contains live mensenchymal precursor cells
  • Antigenicity
    • Allograft is a composite material and therefore has many potential antigens (cell surface glycoproteins)
      • Class I and Class II antigens on graft are recognized by host T lymphocytes and elicit an immune response
      • immunogenic cells are marrow-based, endothelium, and retinacular-activating cells
        • bone marrow cells elicit the greatest immune response
        • extracellular matrix also acts as an antigen
          • type I collagen stimulates both humoral and cell-mediated responses
          • noncollagenous matrix (proteoglycans, osteocalcin)
      • hydroxyapatite has not been shown to elicit an immune response
        • primary rejection is cell-mediated related to the major histocompatibility complex (MHC) incompatibility
  • Overview
      • Types of Autograft
      • Cancellous
      • Less structural support
      • Greater osteoconduction
      • Rapid incorporation via creeping substitution
      • Cortical
      • Slower incorporation due to need to remodel existing Haversion canals
      • Interstitial lamellae preserved
      • Provides more structural support
      • 25% of massive grafts sustain insufficiency fractures
      • Vascularized bone graft
      • Technically challenging with quicker union and cell preservation
      • Examples include: free fibula strut graft (peroneal artery), free iliac crest (deep circumflex iliac arteries), distal radius used for scaphoid fx (1-2 intercompartmental superretinacular artery branch of radial artery)
      • Types of Allograft
      •  Highest risk of disease transmission and immunogenicity
      • BMP preserved and therefore osteoinductive
      • Fresh frozen
      • Less immunogenicity than fresh
      • BMP preserved and therefore osteoinductive
      • Freeze dried (croutons)
      • Least immunogenic
      • Least structural integrity
      • BMP depleted (purely osteoconductive)
      • Lowest likelihood of viral transmission
      • Type of synthetics
      • Silicate based grafts
      • Aluminum oxide
      • Alumina ceramic bonds bind to bone in response to stress and strain
      • Calcium phosphate
      •  Osteoconduction and osteointegration
      •  Biodegrade very slowly
      •  Highest compressive strength
      •  Many prepared as ceramics (heated to fuse into crystals)
      •  Examples include: tricalcium phosphate, Norian (Synthes), hydroxyapatitie (tradename Collagraft by Zimmer), MONTAGE
      • Osteoconductive only
      •  Quick resorption
      • Examples include: OsteoSet (Wright medical)
      • Coralline hydroxyapatine
      • Calcium carbonate skeleton is converted to calcium phosphate via a thermoexchange process (Interpore)
      • Calcium carbonate
      • Chemically unaltered marine coral
      • Osteoconductive
      • Examples include: Biocora (Inoteb, france)
      • DBM and Bone Growth Factors 
      • Osteoinductive and osteoconductive
      • Contains: collagen, bone morphogenetic proteins, transforming growth factor-beta, residual calcium
      • Does NOT contain mesenchymal precursor cells
      • BMP
      • TGF-B
      • IGF-II
      • PDGF
      • see Rank-L and Bone Growth Factors
  • Autograft
    • Bone graft transferred from one body site to another in the same patient
    • Indications
      • gold standard
    • Properties
      • osteogenic, osteoinductive, and osteoconductive
      • least immunogenic
      • cortical, cancellous, or corticocancellous
      • vascular or nonvascular
    • Donor sites
      • bone marrow aspirate
        • source of osteogenic mesenchymal precursor cells
        • iliac crest and vertebral body most common sites
        • variable number of cells depending on patient age
      • iliac crest is the most common site for autograft
        • provides both cancellous and cortical graft
        • higher complication rate with anterior versus posterior harvesting
        • increased stem cell concentration with posterior harvesting
        • 2% to 36% complication rate
          • blood loss and hematoma
          • injury to superior gluteal artery
          • injury to lateral femoral cutaneous or cluneal nerves
          • hernia formation
          • infection
          • fracture
          • cosmetic defect
          • chronic pain
      • fibula and ribs are most common sources of vascularized autografts
      • tibial metaphysis
  • Allograft
    • Bone graft obtained from a cadaver and inserted after processing
    • Most commonly used bone substitute
    • Properties
      • osteoconductive only due to lack of viable cells
        • the degree of osteoconduction available depends on the processing method (fresh, frozen, or freeze-dried) and type of graft (cortical or cancellous)
      • cortical, cancellous, corticocancellous, and osteoarticular (tumor surgery)
    • Osteoarticular allograft
      • immunogenic
      • preserved with glycerol or dimethyl sulfoxide (DMSO)
      • cryogenically preserved (few viable chondrocytes remain)
      • tissue-matched (syngeneic) grafts decrease immunogenicity
    • Processing methods
      • debridement of soft tissue, wash with ethanol (remove live cells), gamma irradiation (sterilization)
        • dose-dependent higher doses of irradiation kills bacteria and viruses but may impair biomechanical properties
      • fresh allograft
        • cleansing and processing removes cells and decreases the immune response improving incorporation
        • indications
          • rarely used due to disease transmission and immune response of recipient
      • frozen or freeze-dried
        • reduces immunogenicity while maintaining osteoconductive properties
        • reduces osteoinductive capabilities
        • shelf life
          • two years for fresh frozen stored at -20 degrees C
          • five years for fresh frozen stored at -70 degrees C
          • indefinite for freeze-dried
  • Demineralized bone matrix (DBM)
    • Acidic extraction of bone matrix from allograft
      • removes the minerals and leaves the collagenous and noncollagenous structure and proteins
    • Properties
      • osteoconductive without structural support
      • osteoinductive despite loss of some osteoinductive molecules
      • interproduct and interlot variability is common
  • Synthetics
    • Alternative to autografts and allografts
    • Various compositions available (see summary above)
    • Made in powder, pellet, or putty form
    • Properties
    • Outcomes
      • Level I evidence shows that calcium-phosphate bone substitutes allow for bone defect filling, early rehabilitation, and prevention of articular subsidence in distal radius and tibial plateau fractures
  • Bone morphogenetic proteins (BMP)
    • Osteoinductive properties solely
      • stimulates undifferentiated perivascular mesenchymal cells to differentiate into osteoblasts through serine-threonine kinase receptors
      • Platelet rich plasma (PRP) (like other BMPs) solely osteoinductive
      • rhBMP-2 and rhBMP-7 are FDA-approved for application in long bones and spine
    • Complications
      • under or overproduction of bone
      • inflammatory responses
      • early bone resorption
  • Reamer Aspirator Irrigator
    • Provides large volume of bone graft from intramedullary source
      • femur (most common)
      • tibia
    • Possible iatrogenic complications
      • femoral shaft fracture due to eccentric reaming
      • insertion site pain (hip abductors)
  • Graft Healing
      • Stages of Graft Healing
      • Stage
      • Characteristics
      • 1. Inflammation
      • Necrotic debris stimulates chemotaxis
      • 2. Osteoblast differentiation
      • Differentiates from mesenchymal precursor cells
      • 3. Osteoinduction
      • Stimulation of osteoblast and osteoclast function
      • 4. Osteoconduction
      • Bone forms around the new scaffold
      • 5. Remodeling
      • Continual process for years
  • Risks & Complications
    • Disease Transmission
      • hepatitis B
        • risk of hepatitis B disease transmission in musculoskeletal fresh-frozen allograft transplantation is 1 in 63,000
      • hepatitis C
        • risk of hepatitis C disease transmission in musculoskeletal fresh-frozen allograft transplantation is 1 in 100,000
      • HIV
        • risk of transmission of HIV in fresh-frozen allograft bone is 1 in 1,000,000 to 1,670,000
      • allografts are tested for HIV, HBV, HCV, HTLV-1, and syphilis
    • Serous wound drainage
      • calcium sulfate bone graft substitute associated with increased serous wound drainage
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