Original submissionIn vivo evaluation of calcium sulfate as a bone graft substitute for lumbar spinal fusion☆,☆☆,★,★★
Introduction
Spinal fusion has become an accepted method of treatment in select patients with disorders of the lumbar spine [1]. With the advancing age of the current population, the number of patients undergoing these procedures in the future will likely increase. The most commonly performed stabilization procedure of the lumbar spine is a posterolateral intertransverse process fusion 2, 3. Despite this procedure's acceptance, nonunion rates of 5% to 35% have been reported 2, 3. The mechanical environment (loading and stability), fusion site preparation, blood supply, and bone graft source and quantity have all been implicated as local factors important to successful fusion 4, 5. Systemic factors, such as osteoporosis, the patient's hormonal and nutritional status and cigarette smoking, are also important variables affecting fusion rates and clinical success.
Autologous bone graft is considered the gold standard for fusion procedures, but complication rates reaching 30% have been reported after harvest of this material 6, 7, 8, 9, and quantities are limited. Allograft bone, although available in large quantities, has been demonstrated to have variable success in achieving spinal fusion independently 10, 11. Internal fixation has been shown to increase rates of fusion in some studies [4]. Recently, investigators have turned to the examination of other methods, such as biologic enhancement [12], to improve results of spinal fusion. Various types and combinations of bone graft materials 10, 13, 14, 15, 16, 17, 18, electrical stimulation 19, 20, ultrasound [21] and growth factors 2, 3, 14, 22, 23, 24, 25, 26 have been the subject of numerous investigations.
Our group 19, 21 and many other investigators have explored the use of bone graft substitutes and graft extenders using a number of animal models [26]. These materials act as osteoconductive agents, or scaffolds, for bone incorporation but require some other factor to act as an osteoinductive agent [12]. A variety of osteoinductive agents have been investigated, including autologous bone marrow aspirate [27], various forms of demineralized bone matrix, bovine-derived and human recombinant bone morphogenic proteins, TGFa, LMP-1 gene therapy, electrical stimulation and ultrasound.
The rate of resorption of a bone graft substitute may play an important role in a successful, robust fusion. A material that is not resorbed, or resorbed over a prolonged time, would result in less space for the fusion mass to form and hence a weaker fusion for any given volume. On the other hand, a graft material that was designed to resorb in a coordinated manner with that of new bone formation would be beneficial. As new bone formed on the scaffold, the scaffold would, in effect, be taken away.
Calcium sulfate's successful use either alone or in combination with other materials has been demonstrated in well-vascularized regions with surrounding periosteum, such as long bone defects, the calvaria and the mandible. Although others have suggested the use of calcium sulfate as a bone graft substitute in posterolateral spine fusion, we have found no reports in the literature of its experimental use in animals.
In a recent report from this laboratory, Bozic et al. [19] demonstrated that coralline hydroxyapatite used in conjunction with direct-current electrical stimulation increased fusion rates in a dose-dependent manner in the rabbit spinal fusion model, without the need to harvest autologous bone graft. We wished to examine the same in vivo model with a bone graft substitute that has a much faster resorption profile than that of coralline hydroxyapatite. We hypothesized that calcium sulfate, with autologous iliac crest bone marrow aspirate, would be an effective bone graft substitute and that the addition of direct current electrical stimulation would show a dose-dependent response in augmenting new bone formation.
Section snippets
General design
The institutional review board for animal research at our institution approved this study. The animal care was performed in accordance with National Institutes of Health guidelines. Three groups of 12 New Zealand White rabbits (4.0–4.5 kg) were used. Each animal was randomized to one of the following three groups: In Group 1, bilateral L5–6 intertransverse process fusion was attempted using 3 cc of calcium sulfate pellets bilaterally (OsteoSet, 3.0 mm diameter; Wright Medical Technology, Inc.,
Results
One rabbit from Group 1 died from intraoperative anesthetic complications and was replaced with a subsequent animal. Two rabbits died postoperatively, one in Group 1 and one in Group 2, leaving 11 animals in Groups 1 and 2 and 12 animals in Group 3. There were two superficial infections, which were treated effectively with a short course of antibiotic therapy. There were no postoperative neurological complications.
Discussion
The rabbit spinal fusion model described by Boden et al. (1995) 2, 3 is valuable, because it allows for relatively rapid evaluation of alterations in experimental parameters. These investigators showed clinically detectable fusion in only 5 to 6 weeks after autologous iliac crest bone graft application, with no further successful fusions in the ensuing 4 to 6 weeks.
Calcium sulfate has been used successfully to fill bony defects for more than 100 years. In a review published in 1961, Peltier [17]
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FDA device/drug status: Approved for this indication (Ostcoset, Wright Medical Technology).
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FDA device/drug status: Investigational/not approved (Bone stimulator 100ua).
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Support in part or in whole was received from Biomet/EBI, Inc.
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Author PAG acknowledges a financial relationship which may indirectly relate to the subject of this manuscript.