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Bone Graft and Bone Graft Substitutes

Bone Graft and Bone Graft Substitutes. Brad Meulenkamp Academic Half Day September 2012. Acknowledgements. Dr. Sacevich JBJS OTA JAAOS. Overview. Properties Mechanism of Action Bone Grafts Bone Graft Substitutes OITE. Bone Graft Properties. Function in Trauma Mechanical Support

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Bone Graft and Bone Graft Substitutes

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  1. Bone Graft and Bone Graft Substitutes Brad Meulenkamp Academic Half Day September 2012

  2. Acknowledgements • Dr. Sacevich • JBJS • OTA • JAAOS

  3. Overview • Properties • Mechanism of Action • Bone Grafts • Bone Graft Substitutes • OITE

  4. Bone Graft Properties • Function in Trauma • Mechanical Support • Impaction • Void Filler • Segmental defects • Improve Fracture healing • Non-union • Arthrodesis

  5. OITE • (OBQ04-274) Which of the following substances is osteoinductive? • 1. Calcium phosphate • 2. Hydroxyapatite • 3. Collagen-based matrix • 4. Cancellous allograft • 5. Cancellousautograft

  6. Bone Graft Properties • Osteoconduction • Scaffold on which bone and bone-forming cells can attach • Osteoinduction • Stimulation of undifferentiated mesenchymal cells to differentiate along the chondro-osteogenicpathway • Osteogenic • Generation of new bone directly by transplanted bone-forming cells

  7. Mechanism of Action • Hematoma Formation • Local release of cytokines and GFs • Inflammation • Fibrovascular tissue formation • Vascular Ingrowth • Haversian system remodelling • Osteoclasicresorption of graft • Enchondral bone formation

  8. Autograft • Current gold standard for void filler, healing augmentation • Osteoinductive, osteoconductive, osteogenic • Limited by volume, donor site morbidity, surgical time • BUT • There has never been any study comparing autograft to control (ie. wound bed preparation) • Overall: Grade C recomendations

  9. Autograft • Cortical • Osteoconductive • Provide immediate stability in structural defects • Weaken by 6 months, regain strength by 12 months • Cancellous • Osteoconductive, osteoinductive, osteogenic • Minimal structural support • Rapid incorporation and remodeling (creeping substitution) • Vascularized by 2 days

  10. Autograft • Potential harvest sites • Iliac Crest • Tibial Metaphysis • Distal Radius • Greater Trochanter • RIA

  11. Autograft • Iliac Crest • Anterior • Max Volume13 ml • Posterior • Max Volume 30 ml • Acetabular reamer • Max Volume 90 ml (morcellizedcorticocancellous)

  12. ICBG Complications

  13. Reamer Irrigator Aspirator (RIA) • Developed to decompress canal in effort to decrease pulmonary complications • Able to harverst 90 ml of graft • Early studies • Similar cell populations as ICBG • Efficacy equal ICBG • Less harvest site pain

  14. RIA • Technique • Antegrade or retrograde femur, tibia • Template isthmus size to choose reamer head • Ream max 2mm of IM cortices • Ensure concentric placement of guidewire • Can bend to harvest condyles • Filter captures filtrate and graft

  15. RIA • Complications • Blood loss • 12.5% transfusion rate • Incarceration within canal • HD compromize • Iatrogenic fracture 4% • Risk increased in osteoporotic bone

  16. Allograft • Osteoconductive, +/- Osteoinductive • Processing removes most inductive properties • Cortical graft incorporation via creeping substitution and intramembranous bone formation • Cancellous graft incorporates via enchondral bone formation

  17. Allograft • Options • Fresh • High immunogenicity, limited use • Fresh Frozen • Less antigenic • Retains mechanical properties • Shelf life: 1 year at -20°, 5 years at -70° • Freeze-dried • Least antigenic • Dehydrated and vaccumpacking • Shelf life: 5 years at room temp

  18. Osteoconductive Bone Substitutes • Coralline Hydroxyapatite • Collagen Based Matrices • Calcium Sulfate • Calcium Phosphate • TriCalcium Phosphate

  19. OITE • (OBQ11-48) Which of the following is true of both calcium phosphate and calcium sulfate? • 1. They have high resistance to shear forces • 2. They have high resistance to torsional forces • 3. They are contraindicated in spinal fusion • 4. They provide a scaffold for local growth factors • 5. They are not biocompatible with stainless steel orthopedic implants

  20. Osteoconductive Bone Substitutes • Properties • Pore size • Potential Roles • Extender • Adjunct to autograft for large defects • Enhancer • Improve success of autograft • Substitute • Replace autograft

  21. Coralline Hydroxyapatite • Produced from marine coral, goniopora • Chemically converted to HA • Porosity closely resembles that of cancellous bone • Allows for bone ingrowth (25% -48% on biposy) Cancellous bone Goniopora Hydroxyapatite

  22. Coralline Hydroxyapatite • Sold as Pro Osteon (Interpore Cross) • Blocks or pellets • Compressive Strength • Slightly greater than cancellous bone • Resorption Rate • ? Never, >10yrs • HA shell  12 months

  23. Collagen Based Matrices • Xenograft of Bovine Fibrillar Collagen • Acts as scaffold for bone marrow, additives (HA, Tricalcium phosphate) • Sold as: Collagraft(Zimmer), Healos (Depuy) • Strips used for cortical defects • Allows bone ingrowth • Compressive strength • Less than cancellousbone • Resorption • Depends on additive

  24. Collagen Based Matrices • Evidence • Chapman et al. JBJS 1997 • Prospective RCT • Autograft vs. Bovine collagen composite + Bone Marrow in treating long bone fractures • No difference in union, functional outcomes at 24 months • 10% developed anti-bovine antibodies • Warning: Immunogenicity

  25. OITE • A 20-year-old male is involved in motor vehicle collision and sustains a depressed tibial plateau fracture. When performing surgery, if calcium sulfate is used as the primary bone substitute void filler, an increase in which of the following outcomes may be expected as compared to autograft? • 1. Increased complications due to serous drainage • 2. Improved clinical outcomes as shown by more rapid time to healing • 3. Improved clinical outcomes as shown by SF-36 scores • 4. Increased complications due to autoimmune reactions and graft rejection • 5. Equivalent complication rates and clinical outcomes

  26. Calcium Sulfate • Plaster of Paris • Sold as Osteoset(Wright), many others • Pellet or injectable paste form • Compressive Strength • Similar to cancellous bone • Resorption • Very fast – 4 -12 weeks

  27. Calcium Sulfate • Uses • Largely as a graft extender (void filler) • Compressive strength limits role in structural support • Injectible form may increase screw purchase • Antibiotic delivery vehicle • Tobramycin additive • Used in (potentially) infected spaces • Warning: Sterile wound drainage

  28. Calcium Sulfate • D • Osteoset-T vs. tobra-impregnated PMMA • Similar infection and infected non-union eradication with less re-operation

  29. Calcium Phosphate • Available as ceramics, powders, or injectable cements • Sold as Norian(Synthes), α-BSM (Dupuy), ProDense(Wright) • Replaced by lamellar bone via osteoclastic resorption, vascular invasion (True replacement) • Compressive strength: 4-10 X cancellous bone • Resorption time: Slow – 18-24 months • Warning: joint migration

  30. Calcium Phosphate • Advantage: custom fill defects with excellent compressive strength • Many positive studies in: • Distal radius fractures • Improved grip strength, ROM, overall function • Tibial plateau fractures • Less loss of reduction • Calcaneus fractures • Earlier weight bearing • Femoral neck fractures • Less loss of reduction

  31. Calcium Phosphate • c

  32. Calcium Phosphate • 120 Tibial Plateau Fractures (Schatzker II-V) • 82 randomized to α-BSM (Dupuy) • 38 randomized to ICBG • All patients allowed PWB of 50lbs immediately post-op • No difference in baseline characteristics • Age, BMI, Schatzker class, injury mechanism, defect size • Fracture subsidence (>2mm) at 1 year • 30% in ICBG group • 9% in α-BSM group • p=0.009

  33. Tricalcium Phosphate • Available as blocks, granules • Sold as Vitoss(Orthovita), Cellplex TCP (Wright), many others • Compressive strength • Similar to cancellous bone • Resorption • 6-18 months

  34. Tricalcium Phosphate • Porosity • 75% 100-1000μm • Excellent for ingrowth • 25% 1-99μm • Thought to enhance fluid flow through matrix • ? Impoves metabolic environment • Use • Bone graft extenders • Blocks as Substitute for non-contained defects

  35. OITE • Which of the following osteoconductive bone graft substitutes resorbs faster than the rate at which bone growth occurs? • 1. Coralline hydroxyapatite • 2. Collagen-based matrix with hydroxyapatitie coating • 3. Calcium phosphate • 4. Calcium sulfate • 5. Tricalcium phosphate

  36. Osteoinductive Bone Substitutes • Demineralized Bone Matrix • Bone Morphogenic Proteins

  37. Demineralized Bone Matrix • Allogenic Bone minus the structural component • Acid extraction of BMPs, GFs, Type-1 collagen, other proteins • Proposed mechanism • Increased surface area for cell attachment • Viability of Inductive proteins • Some evidence of osteoinduction in animal models • Level of Evidence – IV

  38. Demineralized Bone Matrix • Uses • Spinal fusion • Extender with autograft, allograft • Controversies • Variable forms, content • BMP content varies by donor, tissue bank • Cost • With carrier  $1300/10cc • Without carrier  $500/10cc

  39. Bone Morphogenic Proteins • Members of TGF-βsuperfamily • Expressed early in fracture healing • Act on stem cells, osteoblast, osteoclasts, myoblasts, fibroblasts, neural cells, bone marrow stromal cells • Stimulate mesenchymal differentiation to osteochondroblastics lineage • Early studies (Urist, 1965) used cadaveric • Now produced using recombinant technology • rhBMP-2 (Infuse, Medtronics) • rhBMP-7 (OP-1, Stryker)

  40. Bone Morphogenic Proteins • Uses • rhBMP-2 (INFUSE) • Acts day 1-21 (mesenchymal cell recruitment) • Approved for use in open tibial fractures, anterior lumbar interbody fusion • rhBMP-7 (OP-1) • Acts day 14-21 (activates mature osteoblasts) • Approved for use in long bone non-union

  41. BMP-2 s

  42. BMP-2 • BESTT Study • 450 open tibial shaft fractures treated with IM Nail • Control • 6 mg BMP-2 • 12 mg BMP-2 • 12 mg group 59% RRR of Non-union at 1 year • Less overall re-operation • Accelerated union time • Improved wound healing with less infections • Conclusions: BMP-2 leads to less secondary interventions in open tibial fractures

  43. BMP-7 Friedlander et al. JBJS 2001 • 124 Tibial Non-Unions • Reamed IM Nail with OP-1 vs. Autograft • 9 month follow up  No difference • OP-1 – 81% union • Autograft – 85% union • Less infections in OP-1 group • Conclusion: BMP-7 is a safe and effective alternative to autograft • *** No control group (reamed IM Nail alone)

  44. Summary • Many options exist • We don’t know very much • BMP’s show good promise • Big business

  45. OITE • (OBQ06-176) Iliac crest cancellous bone graft can be harvested from either the anterior or posterior aspect of the pelvis. When comparing these two locations, harvesting from the anterior iliac crest has • 1. Less severe postoperative pain at the surgical site • 2. A lower complication rate than posterior harvesting • 3. A higher complication rate than posterior harvesting • 4. The same complication rate as posterior harvesting • 5. None of the above.

  46. OITE • (OBQ06-273) Which of the following bone graft material contains live mesenchymalosteoblastic precursor cells? • 1. fresh-frozen allograft bone • 2. recombinant bone morphogenic protein • 3. demineralized bone matrix • 4. autologous iliac crest marrow aspirate • 5. calcium phosphate putty

  47. The End

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