Introduction
Fusion is an important part in spinal surgery, be it in the cervical spine or in the lumbosacral spine. Also, in large deformity cases fusing all the spinal segments involved is necessary. This needs large amount of bone graft. Procurement of bone graft from the patient (autograft) is standard practice. However, substituting with other products have taken importance in recent years. This article gives an overview of different types of bone graft and its substitutes available for spinal surgeons during spinal surgery.
Bone graft properties
Before going into the intricacies of bone graft and its substitutes it is important for the reader to understand how each product is helping to achieve spinal fusion. Each product may have one or more of the following properties all of which is needed in achieving a strong solid fusion.
- Osteoconduction - Provides scaffolding and matrix needed for new bone to grow on
- Osteoinduction - Proteins and growth factors induce or stimulate bone to grow
- Osteogenicity - Transmittal of osteoblasts or live bone cells
- Structural support - Giving strength to hold until new bone gets strength
Types of Bone graft & its substitutes
- Autograft
- Allograft
- Bone graft substitutes, and
- Osteoinductive agents
Autograft
Autograft is the gold standard for fusion in spinal surgery (like in other specialties) against which the others are measured. It is osteoconductive, osteoinductive and also osteogenic. It can be cancellous or cortical or corticocancellous. Commonly, the cancellous bone graft is procured from the posterior iliac crest. Also, the iliac crest gives corticocancellous graft as well when it can be used in cervical spine. Further, during posterior spinal decompression the posterior elements of spine removed as part of the process can be nibbled and packed as bone graft. Cancellous autograft has the disadvantage of poor structural support. Cortical bone graft has all the qualities like a cancellous bone graft, however, as they are biologically less active, they are inferior compared to the cancellous bone graft except structural support. Cancellous autograft gets rapidly incorporated than a cortical autograft. Cortical autograft can be either nonvascular or vascular. In spinal surgery frequently it is nonvascular fibular graft which is used to give structural support. Fibular struts or rib struts may be used to fill in the space created by voids resulting from vertebrectomies and also in transacral fixation of high grade spondylolisthesis. Also to note, autogenous bone grafting is the only source of osteoprogenitor cells apart from bone marrow aspiration. In normal marrow, 1 per 50000 nucleated bone marrow cells is an osteoprogenitor cell. This can be increased by concentrating them in a centrifuge. The limitations of autogenous bone graft are its limited supply, and the donor site morbidity associated with its procurement.
Allograft
Allograft can be cancellous, cortical or corticocancellous like autograft. They are available as fresh, fresh frozen or freeze-dried. The disadvantage in general for any allograft is infection (esp. Slow virus infection). Unlike autograft, allograft does not have osteogenic cells, but has the advantage of avoiding donor site morbidity.
Fresh allograft:
This is highly antigenic and has got little time to test for infection or immunogenicity. This is seldom used in spinal surgery. The rare indication may be to fill in the void created by en bloc vertebrectomy for tumour in a young child where the fibular graft can be procured from the mother.
Fresh frozen allograft:
This is relatively less antigenic. There is plenty of time to test for infection and immunogenicity. The important advantage is that it preserves the biomechanical properties of the bone graft.
Freeze-dried (lyophilised) allograft:
This is processed by removing water through a vacuum process, and thus reduces the immunogenicity significantly. However, this also degrades the mechanical properties of the bone graft.
Demineralised bone matrix (DBX)
The cortical allograft is subjected to acid extraction to produce decalcification thereby yielding a composite of collagen, noncollagenous proteins and also a low concentration of growth factors. This is the least immunogenic form of the allograft because of extensive preparation. DBX is available in different forms like powder, putty, crushed granules, chips or gel-packed syringes.
In general, the success of allograft fusion depends on its placement, i.e., anterior or posterior. Allograft fusion is quite successful when placed anteriorly (in compression) compared to posterior spinal fusion (neutral load or in tension).
Bone graft substitutes
Bone graft substitutes can act as an extender for autogenous bone graft when used in multiple level fusions or to fill a large space, or as an enhancer to improve the success of autograft, or as a substitute to replace autograft. The rate of resorption depends on the composition, porosity and geometry of the product. Similarly, the mechanical properties of the bone graft substitute vary significantly between products and they depend on the composition of the product.
Ceramics:
These are inorganic preparations that act as scaffolds and are exclusively osteoconductive, and the porous structure is conducive for good bone ingrowth. Even though various products are available under this category, only hydroxyapatite and tricalcium phosphate or a combination of the two is used in spinal surgery. Also, coralline hydroxyapatite and calcium carbonate are different ceramics used in spinal surgery.
There are three types of ceramics:
- Sintered
- Replamiform, and
- Collagen mesh.
The advantages of ceramic bone graft substitute include the absence of inflammatory response, and no risk of disease transmission. However, it is difficult to assess the radiographic fusion as it is radio-opaque on X-ray, and that it persists for a long time even though it is biodegradable. Bone remodelling is different when ceramics are used as the resorbing cell is a foreign body giant cell and not an osteoclast. Ceramic materials in general do not lose structural integrity with sterilisation procedures.
Hydroxyapatite is the natural mineral composition of bone, but produced from marine coral exoskeletons hydrothermically, and they both have similar porosity appearance. Tricalcium phosphate is biocompatible and bioabsorbable but it is brittle with low impact resistance. Examples of products available are Vitoss (orthovita), chronos (synthes), etc. Calcium phosphate (Norian (Synthes), Alpha BSM (DePuy)) are available as injectable forms and gets high compressive strength once it hardens. Calcium sulphate in general, has low compressive strength and does not give structural support. Examples are osteoset, bone blast, etc. They are available as pellets, bead kits, and in injectable forms.
Synthetic polymer:
Cortoss is a synthetic polymer which is used in the treatment of vertebral compression fractures, and also in vertebral augmentation and screw augmentation.
Bone morphogenetic proteins
BMPs are useful for osteoinduction and stem cell differentiation. They are produced by recombinant technology, and the clinically available forms are rhBMP-2 and rhBMP-7. Apart from recombinant technology, BMPs can be produced from human or bovine bone as well. BMPs cannot be used alone as they tend to diffuse away from the fusion site thereby losing it osteoinductive capacity. Recent literature evidence shows equivalent or better fusion masses when BMP is added with autogenous bone graft and also with superior biomechanical properties of the resultant fusion mass.
Bone marrow injection
Osteoprogenitor cells and growth factors are present in unfractionated bone marrow and mesenchymal cells and hence, may be useful in achieving bone fusion in spinal surgery. Currently, this is practised in long bone fracture nonunions where the fracture is stabilised with rigid internal or external fixation. Its function in spinal surgery for providing enhanced fusion mass still needs to be established by clinical trials.
Autologous platelet concentrate
Platelet concentrate contain a collection of signalling molecules with chemotactic and mitogenic proteins but does not have any BMP. Its use in spinal surgery to improve fusion mass is yet to be proved with good clinical trials.
Gene therapy
This is still experimental and may find its place in spinal surgery in future.
References
- Whang PG, Wang JC. Bone graft substitutes for spinal fusion. Spine J. 2003 Mar-Apr;3(2):155-65.
- Berven S, Tay BK, Kleinstueck FS, Bradford DS. Clinical applications of bone graft substitutes in spine surgery: consideration of mineralized and demineralized preparations and growth factor supplementation. Eur Spine J. 2001 Oct;10 Suppl 2:S169-77.
- Vaccaro AR, Chiba K, Heller JG, Patel TCh, Thalgott JS, Truumees E, Fischgrund JS, Craig MR, Berta SC, Wang JC; North American Spine Society for Contemporary Concepts in Spine Care. Bone grafting alternatives in spinal surgery.Spine J. 2002 May-Jun;2(3):206-15.
