Autograft/Allograft/Cage/Bone Morphogenetic Protein





The Use of Autograft and Allograft in Revision Lumbar Spine Surgery


One of the major contributors to a solid spinal arthrodesis is the use of bone grafts. In selecting the appropriate graft, there are three properties that receive consideration: osteoinductivity, osteoconductivity, and osteogenicity. Osteoinductivity describes the ability of the graft to stimulate migration of bone cell precursors that differentiate into osteoblasts and osteoclasts to lay down new bone. Osteoconductivity is the ability of the graft to promote bone growth on the surface of the graft material and osteogenicity is the presence of bone cells that maintain the strength of the growing bone. Grafting can generally be divided into autograft and allograft.


Autograft


Autograft is defined as the use of the patient’s own bone as a graft. This has been traditionally achieved through the use of iliac crest bone graft (ICBG), which is considered the “gold standard” for arthrodesis. Autograft harvested from the iliac crest has distinct advantages in achieving successful arthrodesis. It is harvested at the time of surgery and contains pluripotent stem cells with osteoinductive and osteoconductive growth factors. In addition, the cancellous portion of the ICBG contains channels for vascularization with excellent osteogenic properties that facilitate incorporation at the host site. Furthermore, owing to its tricortical surface, graft harvested from the iliac crest provides immediate structural support and optimal stability when used as a posterior lumbar interbody graft until fusion occurs. Another advantage is that it can be harvested from posteriorly while the patient is prone thus obviating the need for repositioning the patient in the operating room.


However, ICBG is limited in its supply and is associated with donor-site complications such as neuralgic pain and paresthesia when the lateral femoral cutaneous nerve is injured (particularly at risk through an anterior harvest), hematomas that can be life-threatening when large vessels are injured, infections, pelvic fracture, and chronic pain. In fact, donor-site chronic pain can be a major limiting factor in patients’ daily activities, which may negatively impact their overall surgical outcomes. Alternative autograft options to ICBG include the rib, fibula, and vertebral body, but they all have donor-site morbidity, increased blood loss, and increased operating time in common. Therefore autograft use has been mainly reserved for patients who are at risk for pseudarthrosis, for example, those with a prior failed fusion, obesity, diabetes, tobacco use, steroid use, or history of malignancy.


Allograft


An alternative to autologous bone graft is allograft bone, which is harvested from cadaveric tissue donors and is available in abundant quantities. It comes in a variety of forms including fresh-frozen or freeze-dried allograft, and demineralized bone matrix (DBM). In all forms of allograft preparation, cellular debris from dead cells can cause an immune response leading to slower incorporation of the graft and inflammation at the fusion site.


Fresh-frozen allograft is the simplest preparation method, in which the bone graft is harvested and treated with an antibiotic solution and frozen at −70° C. Freeze-dried grafts are also treated with antibiotic solution and frozen with subsequent removal of the vast majority of the water, which allows it to be stored at room temperature. Both fresh-frozen and freeze-dried grafts can serve as structural allografts, although fresh-frozen grafts provide a higher mechanical stability and strength, but carry a higher risk of disease transmission, such as human immunodeficiency virus (HIV; 1 in 1.6 million) and hepatitis B or C, which is still lower than that of a blood transfusion. The lower mechanical stability of freeze-dried allografts makes them more susceptible to fracture. Therefore fresh-frozen grafts are preferred over freeze-dried grafts when structural support is needed. In addition to reducing mechanical stability, freeze-drying allografts diminishes endogenous bone morphogenetic proteins (BMPs), making them less effective in osteoinduction. In a prospective randomized, blinded study that compared the fusion rates between fresh-frozen and freeze-dried allografts in 50 patients using plain radiographs and computed tomography scans at a 2-year follow-up, the fusion rate was greater with fresh-frozen allografts (77% fresh-frozen vs. 65% freeze-dried; the results did not reach statistical significance).


DBM is created from cadaveric bone by acid extraction of the minerals while preserving organic proteins that constitute the bone matrix. It is manufactured in the form of fiber, powder, putty, or sheets and serves as an osteoconductive scaffold because of the type I collagen, noncollagen proteins, and growth factors it contains. It is inexpensive and readily available but cannot be used as a structural graft and has inconsistent osteoinductive properties. It is often used to augment posterolateral fusion and can be particularly useful in patients undergoing revision lumbar fusion to improve fusion rates.


Intervertebral Body Cages in Lumbar Spine Surgery


The removal of the diseased disc, distraction of the disc space, and implantation of an intervertebral body cage can help achieve a more solid arthrodesis, indirect neural decompression, restoration of lordosis, and increased mechanical stability. With advancements in spinal fusion surgery, a variety of cage materials and dimensions have been designed to accommodate numerous lumbar fusion approaches. The center of most cages is hollow and is often filled with autologous, allogenic, or synthetic grafts to enhance fusion.


Cage Materials


The ideal cage is rigid enough to maintain structural stability but with similar elasticity to bone to prevent subsidence or bone fracture. Most cages are made of titanium alloys or polyetheretherketone (PEEK). The advantage of titanium is its biocompatibility because it is an inert material and is resistant to corrosion. In addition, titanium cages have high osteoconductive potential that lead to optimum fusion rates. The drawback stems from the rigidity of the material compared with bone, which can result in endplate fracture and subsequent subsidence. In contrast, PEEK cages have an elastic modulus that is similar to bone, which leads to lower subsidence rates. However, PEEK cages have a hydrophobic surface that may not be optimal for bony trabeculation across the cage. To compare the fusion rates between PEEK and titanium cages, Seaman et al. conducted a meta-analysis and found both materials to have similar fusion rates, but a higher rate of subsidence with titanium cages.


Biological interbody alternatives are cadaveric femoral rings or fibular allografts that can be packed into the disc space to provide structural support. They are readily available at low cost and because of their biological origin and low rigidity, the rate of subsidence is low with good bony integration. There is a potential risk of fracture upon insertion.


Geometry of Interbody Cages


There are a variety of cage shapes including cylindrical, trapezoidal, rectangular, banana-shaped, and others. Cylindrical titanium cages constitute the first generation of interbody devices with a threaded surface that are screwed into position. Although the threaded design provides a shorter fusion time through good bony incorporation, it is associated with higher rates of subsidence and limited distractive height. Trapezoidal cages are often used in anterior lumbar interbody fusion (ALIF) procedures and are a viable option to restore sagittal alignment through the tapered design. Rectangular cages, however, are made for lateral or posterior approaches but their long, flat profile can create segmental kyphosis. Banana-shaped cages have a biconvex shape and are designed for transforaminal approaches, allowing for unilateral placement across midline of the vertebral body. However, because of their more medial and posterior final position, banana-shaped cages have been associated with higher rates of subsidence compared with straight-shaped cages.


Expandable Cages


Expandable cages allow the expansion of the spacer after its deployment within the disc space in situ to optimize fit and reduce endplate damage from insertion of graft trials. They are also advantageous in cases where the corridor into the disc space may be limited by anatomy or the vicinity of neural structures, for example, in transforaminal approaches.


The Use of Bone Morphogenetic Proteins


BMPs were first discovered by Dr. Marshall Urist in 1965. They are bone growth factors that belong to the transforming growth factor beta (TGF-β) superfamily and promote bone formation by inducing mesenchymal stem cells to differentiate into osteoblasts. There are more than 20 types of BMP described, but genetically engineered recombinant human bone morphogenetic protein-2 and -7 (rhBMP-2 and rhBMP-7) are the most widely used in clinical practice. rhBMP-2 was originally US Food and Drug Administration (FDA)-approved for ALIF and made commercially available in 2002. BMPs are soluble proteins that are delivered in combination with carriers to ensure that they do not diffuse away from the site of application and maintain local high concentration to achieve their desired effect. Absorbable collagen sponges and compression-resistant matrix are frequently used carriers. RhBMP-2 in combination with an absorbable collagen sponge (Infuse, Medtronic Sofamor Danek, Memphis, TN) is commercially available and FDA-approved for ALIF only. However, spine surgeons have used it off-label for several other indications including cervical spinal fusions, deformity correction, pediatric spinal fusions, and others. Multiple level I and II studies have shown that the use of rhBMP-2 increases radiographic fusion rates. In a prospective randomized multicenter study, Burkus et al. examined the safety and efficacy of rhBMP-2 absorbable collagen sponge as a replacement for ICBG in ALIF and found that the study group patients had shorter length of surgery, less blood loss, a shorter hospital stay, and significantly better fusion rates. In a multicenter randomized controlled trial, Hurlbert et al. compared the effect of rhBMP-2 with autologous ICBG on radiographic fusion rates and clinical outcome for one- and two-level instrumented posterolateral lumbar fusion surgeries in 197 patients. The authors found higher fusion rates in patients who were treated with rhBMP-2 (94% vs. 69%) at the 4-year follow-up. However, there was no improvement in clinical outcomes between the two groups.


Although BMPs have been widely shown to improve radiographic fusion rates, some concerns have been raised regarding their safety with their routine wide application in spinal fusion surgery. Some of the adverse events associated with their use include uncontrolled bone overgrowth, local tissue reaction (inflammation, edema, wound complications, and infection), radiculitis, carcinogenicity, and negative effects with their use in cases with durotomy. As a result of the aforementioned safety concerns, the FDA issued a Public Health Notification in 2008 to warn about potential life-threatening complications related to rhBMP-2 use in cervical spine fusions. Therefore it is important to use BMP judiciously and only in patients with no contraindications, and to counsel them on the potential risks associated with BMP ( Fig. 10.1 ).


May 5, 2021 | Posted by in NEUROSURGERY | Comments Off on Autograft/Allograft/Cage/Bone Morphogenetic Protein

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