HOW BONE GRAFTS WORK Bone Grafting (Spine and Orthopaedic)

HOW BONE GRAFTS HELP WITH BONE HEALING

Bone grafts assist in the formation of new bone by providing scaffolding, stimulating bone healing, or both to create permanent stabilization.

MECHANISMS OF ACTION

Successful bone healing involves three general mechanisms of action* (MOA): osteogenesis, osteoconduction, and osteoinduction. All three MOAs are necessary for a successful bone grafting procedure, but the bone graft itself does not need to contain all three MOAs. Generally the patient is the best source of osteogenic cells, with osteoconduction serving as a scaffold and osteoinduction as the stimulator for growth.

Osteogenesis

Osteogenesis refers to living cells, such as osteoblasts, that form new bone. The success of any bone grafting procedure is dependent on having enough bone forming or "osteogenic" cells in the area. Iliac crest bone graft (ICBG), a type of autograft contains more Mechanical stem cells than local bone. Local bone, autograft from the surgical site, consists of cortical bone and contains fewer MSCs. However, the presence of mesenchymal stem cells does not make a bone graft osteogenic. These stem cells require a signal, such as BMP, to differentiate into osteoblasts.1

Osteoblasts are living cells that form new bone.

Osteoconduction

Osteoconduction is the ability of materials to serve as a scaffold onto which bone cells can attach, migrate, grow, and divide. In this way, the bone healing response is conducted through the graft site, just as a vine uses a trellis for support. Osteogenic cells generally work much better when they have a matrix or scaffold for attachment. DBMs containing bone fibers produce a greater osteoconductive structure than particles.2 Ceramics are strictly osteoconductive scaffolds and fall in the category of autograft extender or bone void filler.

A passive scaffold allows space for bone to form.

Passive scaffolds maintain space and allow bone formation (200% magnification).

Osteoinduction

Osteoinduction is the capacity of growth factors in the body to attract, proliferate, and differentiate MSCs or immature bone cells into osteoblast to form healthy bone tissue. Most of these signals are part of a group of protein molecules called bone morphogenetic proteins, or BMPs, and are found in normal bone. Highly osteoinductive bone grafts have been evaluated as an autograft alternative in certain indications.†

Active recruitment and stimulation of stem cells differentiate into osteoblasts and form bone.

Active recruitment and stimulation of stem cells differentiate into osteoblasts and form bone.

*

Generally accepted mechanism of action

†

BMPs have been tested as an autograft alternative in multiple clinical studies for certain indications in spine, orthopedic trauma, and dental.3,4,5,6

1

Cuomo AV, et al. Mesenchymal Stem Cell Concentration and Bone Repair: Potential Pitfalls from Bench to Bedside. J Bone Joint Surg Am. 2009; 91:1073–1083.

2

Martin GJ, Boden SD, Titus L, Scarborough NL New Formulations of Demineralized Bone Matrix as a More Effective Graft Alternative in Experimental Posterolateral Lumbar Spine Arthrodesis. Spine. 1999;24(7):637-645.

3

Burkus, et al. Anterior Lumbar Interbody Fusion Using rhBMP-2 With Tapered Interbody Cages. J Spinal Disorders. 2002; 15(5):337-349.

4

Boyne PJ, Lilly LC, et al. De Novo Bone Induction by Recombinant Human Morphogenetic Protein-2 (rhBMP-2) in Maxillary Sinus Floor Augmentation. J Oral Maxillofac Surg. 2005; 63:1693-1707.

5

Fiorellini JP, Howell TH, et al. Randomized Study Evaluating Recombinant Human Bone Morphogenetic Protein-2 for Extraction Socket Augmentation. J Periodontol. 2005; 76(4): 605-613.

6

Friedlaender, et al. Osteogenic Protein-1 (Bone Morphogenetic Protein-7) in the Treatment of Tibial Nonunions: A Prospective, Randomized Clinical Trial Comparing rhOP-1 with Fresh Bone Autograft.

SPINAL INDICATIONS

BRIEF SUMMARY OF INDICATIONS, CONTRAINDICATIONS, AND WARNINGS FOR:
Infuse™ Bone Graft/LT-Cage™ Lumbar Tapered Fusion Device
Infuse™ Bone Graft/Inter Fix™ Threaded Fusion Device
Infuse™ Bone Graft/Inter Fix™ RP Threaded Fusion Device
Infuse™ Bone Graft/Perimeter™ Interbody Fusion Device
Infuse™ Bone Graft/Clydesdale™ Spinal System
Infuse™ Bone Graft/Divergence-L™ Anterior/Oblique Lumbar Fusion System
Infuse™ Bone Graft/Pivox™ Oblique Lateral Spinal System

The Infuse™ Bone Graft/Medtronic Interbody Fusion Device is indicated for spinal fusion procedures in skeletally mature patients with degenerative disc disease (DDD) at one level from L2-S1, who may also have up to Grade I spondylolisthesis or Grade 1 retrolisthesis at the involved level.

The following interbody devices and surgical approaches may be used with Infuse™ Bone Graft:

  • The LT-Cage™ Lumbar Tapered Fusion Device, implanted via an anterior open or an anterior laparoscopic approach at a single level.
  • The Inter Fix™ or Inter Fix™ RP Threaded Fusion Device, implanted via an anterior open approach at a single level.
  • The Perimeter™ Interbody Fusion Device implanted via a retroperitoneal anterior lumbar interbody fusion (ALIF) at a single level from L2-S1 or an oblique lateral interbody fusion (OLIF) approach at a single level from L5-S1.
  • The Clydesdale™ Spinal System, implanted via an OLIF approach at a single level from L2-L5.
  • The Divergence-L™ Anterior/Oblique Lumbar Fusion System interbody device implanted via an ALIF approach at a single level from L2-S1 or an OLIF approach at a single level from L5-S1.
  • The Pivox™ Oblique Lateral Spinal System implanted via an OLIF approach at a single-level from L2-L5.

The Infuse™ Bone Graft/Medtronic Interbody Fusion Device consists of two components containing three parts – a spinal fusion cage, a recombinant human bone morphogenetic protein, and a carrier/scaffold for the bone morphogenetic protein and resulting bone. These components must be used as a system for the prescribed indication described above. The bone morphogenetic protein solution component must not be used without the carrier/scaffold component or with a carrier/scaffold component different from the one described in this document. The Infuse™ Bone Graft component must not be used without the Medtronic Interbody Fusion Device component.

NOTE: The Inter Fix™ Threaded Fusion Device and the Inter Fix™ RP Threaded Fusion Device may be used together to treat a spinal level. The LT-Cage™ Lumbar Tapered Fusion Device, the Perimeter™ Interbody Fusion Device, the Clydesdale™ Spinal System, the Divergence-L™ Anterior/Oblique Lumbar Fusion System, and the Pivox™ Oblique Lateral Spinal System implants are not to be used in conjunction with either the Inter Fix™ OR Inter Fix™ RP implants to treat a spinal level.

The Infuse™ Bone Graft/Medtronic Interbody Fusion Device is contraindicated for patients with a known hypersensitivity to recombinant human Bone Morphogenetic Protein-2, bovine Type I collagen, or to other components of the formulation and should not be used in the vicinity of a resected or extant tumor, in patients with any active malignancy, or patients undergoing treatment for a malignancy; in patients who are skeletally immature; in pregnant women; or in patients with an active infection at the operative site or with an allergy to titanium, titanium alloy, or polyetheretherketone (PEEK).

There are no adequate and well-controlled studies in human pregnant women. In an experimental rabbit study, rhBMP-2 has been shown to elicit antibodies that are capable of crossing the placenta. Women of child bearing potential should be warned by their surgeon of potential risk to a fetus and informed of other possible orthopedic treatments. The safety and effectiveness of this device has not been established in nursing mothers. Women of child- bearing potential should be advised to not become pregnant for one year following treatment with this device.

Please see the Infuse™ Bone Graft package insert for the complete list of indications, warnings, precautions, adverse events, clinical results, definition of DDD, and other important medical information. The package insert also matches the sizes of those sized devices that are indicated for use with the appropriate Infuse™ Bone Graft kit. An electronic version of the package insert may be found at www.medtronic.com/manuals.

CAUTION: Federal (USA) law restricts this device to sale by or on the order of a physician with appropriate training or experience.

TIBIA TRAUMA INDICATIONS

BRIEF SUMMARY OF INDICATIONS, CONTRAINDICATIONS, AND WARNINGS FOR:
INFUSE™ BONE GRAFT

Infuse Bone Graft is indicated for treating acute, open tibial shaft fractures that have been stabilized with IM nail fixation after appropriate wound management. Infuse Bone Graft must be applied within 14 days after the initial fracture. Prospective patients should be skeletally mature.

Infuse Bone Graft consists of two components – recombinant human Bone Morphogenetic Protein-2 solution and a carrier/scaffold for the bone morphogenetic protein solution and resulting bone. These components must be used as a system. The bone morphogenetic protein solution component must not be used without the carrier/scaffold component or with a carrier/scaffold component different from the one described in this document.

Infuse Bone Graft is contraindicated for patients with a known hypersensitivity to recombinant human Bone Morphogenetic Protein-2, bovine Type I collagen or to other components of the formulation and should not be used in the vicinity of a resected or extant tumor, in patients with an active malignancy or patients undergoing treatment for a malignancy. Infuse Bone Graft should also not be used in patients who are skeletally immature, in patients with an inadequate neurovascular status, in patients with compartment syndrome of the affected limb, in pregnant women, or in patients with an active infection at the operative site.

There are no adequate and well controlled studies in human pregnant women. In an experimental rabbit study, rhBMP-2 has been shown to elicit antibodies that are capable of crossing the placenta. Women of child bearing potential should be warned by their surgeon of potential risk to a fetus and informed of other possible orthopedic treatments. The safety and effectiveness of this device has not been established in nursing mothers. Women of child-bearing potential should be advised to not become pregnant for one year following treatment with this device.

Please see the package insert for the complete list of indications, warnings, precautions, adverse events, clinical results, and other important medical information.

CAUTION: Federal (USA) law restricts this device to sale by or on the order of a physician with appropriate training or experience.