In vivo evaluation of calcium sulfate as a bone graft substitute for lumbar spinal fusion

Abstract

Background context: Posterolateral fusions of the lumbar spine have nonunion rates as high as 35%. The availability of autologous bone to promote fusion is limited, particularly for multilevel fusions. Bone substitutes have been proposed to augment or replace autologous bone for spinal surgery. Calcium sulfate offers high porosity, osteoconductivity, and high resorption rate. This material has been used successfully for treatment of long bone defects but has not been investigated as a bone graft substitute for spinal fusions.

Purpose: To determine whether the use of calcium sulfate granules in conjunction with an implantable electrical stimulator is a safe and effective means of attaining spinal fusion. Study design/setting: A rabbit lumbar fusion model was used to assess a calcium sulfate bone graft substitute in combination with electrical stimulation for spinal fusion. Methods: Thirty-six adult New Zealand White female rabbits were divided into three groups. Each group underwent a single-level (L5–L6) fusion, receiving 3.0 cc calcium sulfate granules with bone marrow aspirate from the iliac crest. Group 1 had no electrical stimulator applied. Groups 2 and 3 received a 40-μA (Group 2) or a 100-μA (Group 3) implantable electrical stimulator. The animals were sacrificed at 8 weeks, and the rabbit spines were subjected to radiographic assessment, manual palpation, and mechanical testing. Results: Two rabbits died postoperatively. The radiographic assessment revealed no fusions occurred at the adjacent nonoperated control levels (L4–L5). There were no fusions observed within Group 1, containing the calcium sulfate and bone marrow aspirate alone. The sites with the implantable stimulators showed a dose-dependent increase in fusion stiffness. However, no fusion mass in Group 2 or 3 was graded as bilaterally complete. Conclusion: This study found that calcium sulfate as a bone graft substitute was unsuccessful in promoting spine fusion in a rabbit model. There was radiographic evidence of rapid resorption of the calcium sulfate within 4 weeks after surgery. The use of electrical stimulation created a dose-dependent increase in mechanical competence of the bony mass. However, the addition of direct current (DC) current did not significantly alter fusion rates with calcium sulfate used as the bone graft substitute in this model.

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, TGF_a, 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.