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Bone substitutes

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									Bone Substitutes

   Sune Larsson
          Professor
  Department of Orthopedics
  Uppsala University Hospital
          Uppsala
           Sweden
   Bone grafting



Spine
Spine         Extremities
              Extremities
50%
50%                50%
                   50%
Two main reasons for using
  autologous bone graft
    Bone Graft Substitutes
             products on the market

Structural support
Structural support           Bone formation
””Mechanicalindication”
 Mechanical indication”      ”Biological indication”




                                           Hydroset




       DBX
     Bone Graft Substitutes
Structural support        Bone formation
Structural support
                          ”Biological indication”
 Mechanical indication”
””Mechanicalindication”
            n cts                      c ts
          ha du
         t o                         du
     ore pr                      p ro
   M ed                     ew
     d r                  F
   un
 h
      Bone Graft Substitutes
 Structural support
 Structural support        Bone formation
 ””Mechanicalindication”
  Mechanical indication”   ”Biological indication”


Calciumphosphate                 BMP
Calciumsulphate                  DBM
Structural support
”Mechanical indication”
Calcium - sulphate



             “Plaster of Paris”
      Calcium - sulphate
Calcium-sulphate   Calcium-sulphate
   preformed           injectable
        Calcium - sulphate

                      Biology
                       Good biocompatibility
                       Resorbs within 6-12 weeks




 Bulk Erosion
-like a sugar cube-
         Calcium - sulphate
Advantages
 Good biocompatibility
 Resorbed




                         Disadvantages
                          Limited strength
                          Resorption might be too rapid
                          Few clinical studies
Calcium - phosphate



            “Mimic the mineral
              phase of bone”
     Calcium - phosphate
Calcium-phosphate    Calcium-phosphate
     preformed            injectable




           chronOS
      Calcium - phosphate


In vitro
 osteoclast on CaP
 acts like on bone
 dissolves the CaP
         Calcium - phosphate
                       Biology
                         good biocompatibility
 Norian SRS
                         slow/incomplete resorption
      Hydroset




Surface Erosion
-like a bar of soap-
    Calcium - phosphate


remodelling




              postop   7 years postop
        Calcium - phosphate
Mechanics
   hardens in 5-10 minutes
   compression strength 45-55 Mpa
   bending and shear strength 4-8 MPa

                          200
                                                        Cortical bone
                          180
                                                        Cancellous (high density)
                          160
                                                        Cancellous (Low density)
         Strength (Mpa)




                          140                           CaP
                          120

                          100

                           80

                           60

                           40

                           20

                            0
                                Compression   Tension            Shear
       Calcium - phosphate
Advantages
 osteoconductive
 good biocompatibility
 structural support

                         Disadvantages
                          limited strength in
                          bending and shear
                          slow/incomplete
                          resorption
          β- tricalciumphosphate

            Compared with ”conventional” CaP
chronOS      macropores
             faster resorption (6-9 months)
             ”weaker”
          β- tricalciumphosphate


chronOS    Indications
            filling benign bone cysts
            for positioning and containment of BMP
            …
β- tricalciumphosphate
  filling of benign bone cyst
β- tricalciumphosphate
  filling of benign bone cyst
   β- tricalciumphosphate
       keep BMP in position




After surgery                 3 months
 Calcium - phosphate


Clinical studies
     Calcium - phosphate
Metaphyseal fractures         Indication
  Tibial plateu fractures                  (   )
  Distal radius
  Proximal humerus
  Trokanteric hip fractures
  Calcaneal fractures
  Femoral neck fractures


Screw augmentation
Tibial plateau fractures


               J Orthop Trauma 2002;16(3):143-9




                J Bone and Joint 2003;85-B:68-73
Tibial plateau fractures




                   AAOS 2004;paper 064
  Tibial Plateau Fractures
                 Conclusions

CaP cement provided
 better stability of articular fragment compared to bone
 graft despite more rapid return to full weight-bearing
 less pain until 6 months postop
 better knee score until 6 months postop
Cases
      Tibial Plateau Fractures
      Open augmentation with calcium-phosphate cement



Women
52 year
Skiing injury
Closed
       Tibial Plateau Fractures
       Open augmentation with calcium-phosphate cement


Technique
  Reduction
  Temporary fixation
  Void preparation
  Metal fixation
  Cement injection
       Tibial Plateau Fractures
       Open augmentation with calcium-phosphate cement


Technique
  Reduction
  Temporary fixation
  Void preparation
  Metal fixation
  Cement injection
       Tibial Plateau Fractures
   Percutaneous augmentation with calcium-phosphate cement



Man
49 years
Traffic accident
Schatzker 2
      Tibial Plateau Fractures
  Percutaneous augmentation with calcium-phosphate cement



Man
49 years
Traffic accident
Schatzker 2
       Tibial Plateau Fractures
   Percutaneous augmentation with calcium-phosphate cement

Man
49 years
Traffic accident
Schatzker 2
       Tibial Plateau Fractures
   Percutaneous augmentation with calcium-phosphate cement

Man
49 years
Traffic accident
Schatzker 2
      Bone Graft Substitutes
 Structural support
 Structural support        Bone formation
 ””Mechanicalindication”
  Mechanical indication”   ”Biological indication”


Calciumphosphate                 BMP
Calciumsulphate                  DBM
Demineralized bone matrix


                contains a range of biologically
                active peptids
                osteoinductive
                easy to produce
      Grafton
Demineralized bone matrix

       Grafton
                 Variable efficacy
                  depends on the processing and
                  preservation technique

   ≠       DBX
                  more aggressive processing less
                  biological effect
Demineralized bone matrix

     Summary DBM
      disease transmission?
      variable efficacy
      very limited documentation
      Bone Graft Substitutes
 Structural support
 Structural support        Bone formation
 ””Mechanicalindication”
  Mechanical indication”   ”Biological indication”


Calciumphosphate                 BMP
Calciumsulphate                  DBM
Bone morphogenetic protein
               what it is?

 Small stable proteins
 20 different BMP´s described
 6 with known effect on bone
 BMP-2,6,7,9 most potent in animal models
 Present for instance in bone matrix
                          BMP
              Differentiating factor

                    Chondroblasts
                                                   Endochondral
                                                   bone formation
        BMP

Mesenchymal                                       Intramembranous
 stam cells                                         bone formation
                    Osteoblasts


          Wozney JM (1993) Cellular and Molecular Biology of Bone Ch 4:131-67
     BMP


rhBMP-2
              Two BMP´s
          commercially available


rhBMP-7
                      Mixing
                Osigraft (rhBMP-7)


rhBMP-7 (3.5mg)
Bovine collagen (carrier)
2.5 ml saline/blood
        Application
       Osigraft (rhBMP-7)




”wet sand”
    Mixing
Inductos (rhBMP-2)
Application
Inductos (rhBMP-2)




         Govender et al. JBJS 2002;84A: 2123-34
Bone graft substitutes
         BMP




  Clinical studies
Bone graft substitutes
     Tibial non-unions

                 124
            Tibia non-unions
                 IM nail




           63               61
          OP-1           Autograft

                     Friedlaender et al JBJS 2001
Bone graft substitutes
tibial non-unions healing at 9 months



            63                 61
          OP-1              Autograft




     51/63                            52/61
                  p=0.524
     81%                              85%

                            Friedlaender et al JBJS 2001
Bone graft substitutes
     open tibial fractures

                    437
             Open tibial fractures




                   145                   145
   147                                   IM nail
                  IM nail
  IM nail            +                     +
               6 mg rhBMP-2          12 mg rhBMP-2




                          BESST study group JBJS 2002
          Bone graft substitutes
            open tibial fractures and rhBMP-2



                   Higher dose (12 mg) vs controls
                     fewer interventions due to delayed union
                     faster fracture healing
                     fewer hardware failures




Significant more
reamed nails in
 ”12 mg group”



                                       BESST study group JBJS 2002
Cases
Periprosthetic fracture
 Women 68 years
 Fall outdoors
 Periprosthetic fracture
 Surg 1 - plate fixation
   Failure at 3 months
 Surg 2 - plate fixation and
 autolog bone
 Surg 3 - autolog bone
 transplant due to slow healing
    Failure at 8 months
Periprosthetic fracture
 Women 68 years
 Fall outdoors
 Periprosthetic fracture
 Surg 1 - plate fixation
   Failure at 3 months
 Surg 2 - plate fixation and
 autolog bone
 Surg 3 - autolog bone
 transplant due to slow healing
   Failure at 8 months after Surg 2
 Surg 4 -plate (DCS) and BMP
Periprosthetic fracture
 Women 68 years
 Fall outdoors
 Periprosthetic fracture
 Surg 1 - plate fixation
   Failure at 3 months
 Surg 2 - plate fixation and
 autolog bone
 Surg 3 - autolog bone
 transplant due to slow healing
   Failure at 8 months after Surg 2
                                      7 months
 Surg 4 -plate (DCS) and BMP
Clavicula nonunion
  male 58 years
  clavicula fracture
  malunion after
  nonoperative treatment
  osteotomy and plate
  fixation – no healing
  reoperation with new
  plate and bone graft -
  no healing
  reoperation with IM nail
  and bone graft - no
  healing
Clavicula nonunion
 male 58 years
 clavicula fracture
 malunion after nonoperative
 treatment
 osteotomy and plate fixation
 non-union
 reoperation with new plate and
 bone graft - no healing
 reoperation with IM nail and bone
 graft - no healing
 Reoperation with plate and BMP
Clavicula nonunion
 male 58 years
 clavicula fracture
 malunion after nonoperative
 treatment
 osteotomy and plate fixation
 non-union
 reoperation with new plate and
 bone graft - no healing
 reoperation with IM nail and bone
 graft - no healing
 Reoperation with plate and BMP
 Healed at 3 months
Humeral nonunion

 woman 67 years
 radiation treatment for
 breast cancer 10 years ago
 traffic accident 3 years ago
 closed fracture
 three previous surgical
 procedures
Humeral nonunion

 revision
 plate
 BMP
 β- TCP
Humeral nonunion

 3 months
 healed
 β - TCP
 resorbed
Humeral nonunion
 man 50 years
 non-union after conservative
 treatment
 no healing after 2 operations
 severe pain and Instability
 heavy smoker
Humeral nonunion

 3 months healed

 4 months complaining of
 ”hard” soft tissues
 ”Ectopic” bone
 Inadequate containment
 of the BMP?
    Containment of BMP
can be a problem due to small volume
                   rhBMP’s

Advantages
 synthetic (rhBMP)
 predictable quality
 unlimited amount      Disadvantages
                        carrier not optimal
                        not injectable
                        still limited amount of
                        clinical results
                        expensive
       Bone graft substitutes
                      Summary

Growing number of different substitutes available

”Mechanical” substitutes dominated by
  Calcium-sulphate
  Calcium-phosphate

”Bone inductive” substitutes dominated by
  BMP-2 och BMP-7
  Demineralized bone matrix
        Bone graft substitutes
                        Future

Accumulate more clinical experience
Determine correct indications

Different substitutes for different indications
Bone grafting will be in part replaced by
substitutes



                           Here to stay

								
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