Biologics in Spine Arthrodesis
Joseph A. Weiner
Wellington K. Hsu
Spine arthrodesis is frequently performed in the treatment of spine trauma, tumors, and complex degenerative disorders. With an estimated 413,000 fusion procedures performed in the United States annually, the number of procedures performed has increased 2.4 times since 1998.1 Failure of fusion, or pseudarthrosis, has been reported at rates as high as 48% in multilevel posterolateral lumbar fusions.2 This motivation, along with the popularity of minimally invasive spine surgery, has led to numerous innovations in the spinal biologics arena, bringing forth new products, research, and applications.3
In a field once dominated by the near-exclusive use of iliac crest bone graft, surgeons are now confronted with a market of numerous biologics, including allograft materials, ceramics, and recombinant growth factors (Table 8.1). All of these products, used in both open and minimally invasive procedures, help to facilitate the clinical goal of achieving arthrodesis. Spine biologics function by altering the local microenvironment surrounding the fusion bed, enhancing fusion-related cellular and molecular activity. These biologics function through three general mechanisms: osteoinduction, osteoconduction, and/or osteogenesis.4 Osteoinduction is the process of stimulating undifferentiated pluripotent stem cells into bone-forming cell lineages. Osteoconduction is described as the donation of biocompatible scaffolding material that provides mechanical structure upon which new bone formation takes place.2 Osteogenesis refers to the contribution of established osteoprogenitor cells directly to bone synthesis. Successful arthrodesis requires a local supply of osteoinductive factors, osteogenic cells to produce bone, and an osteoconductive scaffold to support bone formation.5 Ideally, spinal biologics function to enhance the interplay of these three key mechanisms in an effort to improve spinal arthrodesis while reducing complications.
AUTOGRAFT
Autogenous bone grafting utilizes bone harvested from one area within an individual that is then transplanted to another area from either the same or a distant surgical site. Autograft, specifically iliac crest bone graft (ICBG), provides all of the necessary osteoinductive, osteogenic, and osteoconductive elements and has historically represented the gold standard in relation to spine fusion.6,7 Advantages include complete osteointegration and no risk for immune-mediated rejection. However, concerns remain centered around the limited availability of autograft for large-scale fusions or revision procedures, as well as local donor-site morbidity (Table 8.2).7, 8, 9
Autografts can be divided into two main types: cancellous and cortical. Cancellous grafts have greater osteoconductive, osteoinductive, and osteogenic potential, but possess poor structural properties. Cortical bone has lower biologic potential than cancellous bone, but is also able to provide mechanical support to resist compressive loads.7 Corticocancellous morselized autograft, a blend of both cortical and cancellous bone, offers a large trabecular surface area permitting greater vascular and cellular ingrowth.
Iliac Crest Bone Graft
ICBG provides surgeons with a supply of both cortical and cancellous grafts that can be obtained relatively easily. Generally, the posterior iliac crest is utilized as the donor site for fusion procedures. A large quantity of both cortical and cancellous bone can be harvested via a separate small incision or via an existing posterior spinal incision.10 Reported fusion
rates for iliac crest autograft have varied substantially depending on location of fusion, outcome criteria, patient characteristics, internal fixation, number of fusion levels, and underlying pathology. Anterior cervical fusion rates with iliac crest and plate fixation can exceed 97% while posterior cervical fusion rates have been reported at 93% to 100%.11 Posterolateral lumbar fusion with ICBG tends to be associated with the highest pseudarthrosis rates (89%).12
rates for iliac crest autograft have varied substantially depending on location of fusion, outcome criteria, patient characteristics, internal fixation, number of fusion levels, and underlying pathology. Anterior cervical fusion rates with iliac crest and plate fixation can exceed 97% while posterior cervical fusion rates have been reported at 93% to 100%.11 Posterolateral lumbar fusion with ICBG tends to be associated with the highest pseudarthrosis rates (89%).12
TABLE 8-1. Bone Graft Properties. | ||||||||||||||||||||||||||||
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TABLE 8-2. Advantages and Disadvantages of Available Bone Grafts and Bone Graft Substitutes. | ||||||||||||||||||||||||
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Despite its advantages, the use of ICBG has significant drawbacks, mostly associated with the harvest process. ICBG harvest is occasionally complicated by pain, superficial wound infection, hematoma formation, scarring, sensory abnormalities, graft site fracture, superior gluteal artery injury, donor site hernia, and need for reoperation (Table 8.2).10,13 Several retrospective studies report the rate of complications with ICBG harvest to be between 10% and 39%.10,13, 14, 15 However, these complications have been significantly reduced with alternative techniques such as cortical bone window formation and inner cortex preservation aim to maintain the contour and shape of the iliac crest.14,16
Local Bone Graft
An attractive alternative to harvesting ICBG is to use local bone autograft from the surgical field during an open procedure. Local bone can be harvested from spinous processes, lamina, and facets that are ordinarily removed during the course of a decompression procedure. When compared to ICBG, local graft is associated with a significantly lower complication rate and decreased surgical time.17 While surgeon preference on the use of local bone graft varies, multiple clinical studies demonstrate that for a single-level posterior lumbar fusion, the use of local bone graft can result in equivalent fusion rates when compared to ICBG when the appropriate volume is delivered (Table 8.2).12,18, 19, 20 Studies looking at the use of local bone graft in minimally invasive spine surgery are limited mainly because of the relative supply. Recently, Kasliwal et al. evaluated 40 patients who underwent minimally invasive transforaminal lumbar interbody fusion (MITLIF) with pedicle screw fixation and a cage filled with local bone shavings from a high-speed burr21: 67.5% of patients demonstrated fusion, but clinical outcome was graded as good to excellent in 92% of patients, independent of fusion status.
The use of local bone graft is an efficient use of resources that utilize bone shavings and bone chips generated during surgery. In the case of minimally invasive spinal surgery, the amount of autograft possibly harvested from the lamina and the spinous processes is limited; therefore, bone shavings are often utilized. However, the efficacy of those bone shavings has recently been called into question by Eder et al.22 While it has been established that bone shavings contain viable osteoblasts,22,23 the ability of those osteoblasts to contribute to in vivo spine fusion is significantly lower compared to that of bone chips. In vitro, bone shavings demonstrate decreased osteoblast emigration, mobilization, and mineralization compared to bone chips.22 It is hypothesized that heat necrosis from the high burr rotations per minute (rpm) may lead to the lack of viable cells.24 Although the authors concluded that bone chips are superior in terms of cell delivery, cell proliferation, and mineralization, there is no evidence to conclude that bone shavings provide no benefit. In vivo, Lee et al. demonstrated that local bone graft was unable to induce spine fusion in a rat posterolateral spine model.25
Bone Graft Extenders
Allograft
Allograft refers to tissue transplanted from one individual to another within the same species. Human bone allograft contains an osteoconductive scaffold, lacking both progenitor cells and growth factors, which require it to be used in conjunction with autograft or another osteoinductive agent. Allograft is a popular bone graft extender because of its relative cost, availability, and avoidance of morbidity when compared to autograft. Disadvantages include limited effectiveness when used alone and the potential for disease transmission and immunogenicity (Table 8.2). Allograft, typically harvested from cadaveric tissue, undergoes a rigorous screening process before entering the donor pool. Despite this, there have been case reports of bioincompatibility and disease transmission with allograft use.26
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