Christina Holmes

The biomechanics of pedicle screw augmentation with cement

BACKGROUND CONTEXT A persistent challenge in spine surgery is improving screw fixation in patients with poor bone quality. Augmenting pedicle screw fixation with cement appears to be a promising approach. PURPOSE The purpose of this study was to survey the literature and assess the previous biomechanical studies on pedicle screw augmentation with cement to provide in-depth discussions of the biomechanical benefits of multiple parameters in screw augmentation. STUDY DESIGN/SETTING This is a systematic literature review. METHODS A search of Medline was performed, combining search terms of pedicle screw, augmentation, vertebroplasty, kyphoplasty, polymethylmethacrylate, calcium phosphate, or calcium sulfate. The retrieved articles and their references were reviewed, and articles dealing with biomechanical testing were included in this article. RESULTS Polymethylmethacrylate is an effective material for enhancing pedicle screw fixation in both osteoporosis and revision spine surgery models. Several other calcium ceramics also appear promising, although further work is needed in material development. Although fenestrated screw delivery appears to have some benefits, it results in similar screw fixation to prefilling the cement with a solid screw. Some differences in screw biomechanics were noted with varying cement volume and curing time, and some benefits from a kyphoplasty approach over a vertebroplasty approach have been noted. Additionally, in cadaveric models, cemented-augmented screws were able to be removed, albeit at higher extraction torques, without catastrophic damage to the vertebral body. However, there is a risk of cement extravasation leading to potentially neurological or cardiovascular complications with cement use. A major limitation of these reviewed studies is that biomechanical tests were generally performed at screw implantation or after a limited cyclic loading cycle; thus, the results may not be entirely clinically applicable. This is particularly true in the case of the bioactive calcium ceramics, as these biomechanical studies would not have measured the effects of osseointegration. CONCLUSIONS Polymethylmethacrylate and various calcium ceramics appear promising for the augmentation of pedicle screw fixation biomechanically in both osteoporosis and revision spine surgery models. Further translational studies should be performed, and the results summarized in this review will need to be correlated with the clinical outcomes.

Growth factor-eluting technologies for bone tissue engineering

Growth factors are essential orchestrators of the normal bone fracture healing response. For non-union defects, delivery of exogenous growth factors to the injured site significantly improves healing outcomes. However, current clinical methods for scaffold-based growth factor delivery are fairly rudimentary, and there is a need for greater spatial and temporal regulation to increase their in vivo efficacy. Various approaches used to provide spatiotemporal control of growth factor delivery from bone tissue engineering scaffolds include physical entrapment, chemical binding, surface modifications, biomineralization, micro- and nanoparticle encapsulation, and genetically engineered cells. Here, we provide a brief review of these technologies, describing the fundamental mechanisms used to regulate release kinetics. Examples of their use in pre-clinical studies are discussed, and their capacities to provide tunable, growth factor delivery are compared. These advanced scaffold systems have the potential to provide safer, more effective therapies for bone regeneration than the systems currently employed in the clinic.

Use of S2-Alar-Iliac Screws Associated with Less Complications than Iliac Screws in Adult Lumbosacropelvic Fixation.

Study Design. Retrospective comparative study. Objective. To compare clinical and radiographic outcomes between the S2-alar-iliac (S2AI) and the iliac screw (IS) techniques in the adult population and clarify the clinical strength of S2AI screws. Summary of Background Data. S2AI screws have been described as an alternative method for lumbosacropelvic fixation in place of ISs. The S2AI technique has several advantages with lower prominence, increased ability to directly connect to proximal instrumentation, less extensive dissection of tissue, and enhanced biomechanical strength over the IS technique. However, the clinical significance of these advantages remains unclear. Methods. A single-center retrospective review of patients who underwent lumbosacropelvic fixation yielded 25 IS group patients and 65 S2AI group patients. Baseline demographic information, postoperative complications, pain and functional outcomes, and screw-related outcomes were collected. Results. The S2AI group had lower rates of reoperation (8.8% vs. 48.0%, P < 0.001), surgical site infection (SSI) (1.5% vs. 44.0%, P < 0.001), wound dehiscence (1.5% vs. 36.0%, P < 0.001), and symptomatic screw prominence (0.0% vs. 12.0%, P = 0.02) than the IS group, whereas rates of L5-S1 pseudarthrosis, proximal junctional failure, and sacroiliac joint pain were similar in both groups. Statistically significant pain relief and functional recovery were achieved in both groups without any significant intergroup differences. On multivariate analyses, age [odds ratio (OR) = 0.91, P = 0.004] and S2AI instrumentation (OR = 0.08, P < 0.001) were protective of reoperation, whereas diabetes mellitus (OR = 10.9, P = 0.03) and preoperative diagnosis of tumor (OR = 12.3, P = 0.04) were associated with SSI, and S2AI instrumentation (OR = 0.09, P < 0.001) was protective of SSI. Conclusion. The use of the S2AI technique over the IS technique was an independent predictor of preventing reoperation and SSI, while achieving similar clinical and functional outcomes. Level of Evidence: 4

Quantitative study of parathyroid hormone (1-34) and bone morphogenetic protein-2 on spinal fusion outcomes in a rabbit model of lumbar dorsolateral intertransverse process arthrodesis

Study Design. A posterolateral rabbit spinal fusion model was used to evaluate the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) and teriparatide (PTH [1–34]) used individually and in combination on spinal fusion outcomes. Objective. To test the efficacy of parathyroid hormone on improving spinal fusion outcomes when used with BMP-2. Summary of Background Data. Of the more than 250,000 spinal fusion surgical procedures performed each year, 5% to 35% of these will result in pseudarthrosis. Growing controversy on the efficacy and cost of rhBMP-2 for improving spinal fusion outcomes has presented a challenge for clinicians. Research into PTH as an adjunct therapy to rhBMP-2 for spinal fusion has not yet been investigated. Methods. Forty-eight male New Zealand white rabbits underwent bilateral posterolateral intertransverse process arthrodesis surgery at the L5–L6 level. Animals were divided into 6 groups. Two groups were treated with autograft alone or autograft and PTH (1-34), whereas the other 4 groups were treated with low-dose rhBMP-2 alone, high-dose rhBMP-2 alone, or either dose combined with PTH (1-34). All animals were euthanized 6 weeks after surgery. The L4–L7 spinal segment was removed and assessed using manual palpation, computed tomography (CT), and biomechanical testing. Results. CT assessments revealed fusion in 50% of autograft controls, 75% of autograft PTH (1-34) animals, 87.5% in the 2 groups treated with low-dose rhBMP-2, and 100% in the 2 groups treated with high-dose rhBMP-2. CT volumetric analysis demonstrated that all groups treated with biologics had fusion masses that were on average significantly larger than those observed in the control group (P < 0.0001). Biomechanical data demonstrated no statistical difference between controls, PTH (1-34), and low-dose rhBMP-2 in any testing orientation. PTH (1-34) did not increase bending stiffness when used adjunctively with either low-dose or high-dose rhBMP-2. Conclusion. Although intermittent teriparatide administration results in increased fusion mass volume, it does not improve biomechnical stiffness over use of autograft alone. When delivered concurrently with high- and low-dose rhBMP-2, teriparatide provided no statistically significant improvement in biomechanical stiffness. Level of Evidence: N/A

A systematic assessment of the use of platelet-rich plasma in spinal fusion.

Spinal fusion is one of the most commonly performed procedures for the treatment of spinal instability caused by a multitude of pathologies. However, despite significant advances in spinal instrumentation, failed fusion, or pseudoarthrosis, remains a significant challenge. Therefore, other additives such as bone graft extenders and growth factors have been explored as a method to augment fusion rates. Platelet-rich plasma (PRP) represents an additional approach, as it has shown some promise in bone regeneration. While the general use of PRP in orthopedic applications has been reviewed previously, its use in spinal fusion has not been systematically analyzed. The objective of this review is to systematically discuss the role of PRP in augmentation of bone regeneration for the purpose of spinal fusion. Background information on PRP, including a discussion of its preparation, activation, and growth factors, is included. Additionally, data from in vitro studies utilizing PRP in bone tissue engineering strategies is analyzed, and the available animal and clinical studies are systematically reviewed in order to provide guidance on future research pathways as well as the potential role of PRP in spinal fusion surgery.

Comparison Between S2-Alar-Iliac Screw Fixation and Iliac Screw Fixation in Adult Deformity Surgery: Reoperation Rates and Spinopelvic Parameters

Study Design: Retrospective cohort study. Objective: The S2-alar-iliac (S2AI) technique has been described as an alternative method for pelvic fixation in place of iliac screws (ISs) in spinal deformity surgery. The objective of this study was to analyze the impact of S2AI screws on radiographical outcomes, including spinopelvic parameters. Methods: A retrospective review of 17 patients receiving ISs and 46 patients receiving S2AI screws for correction of adult spinal deformity between 2010 and 2015 with minimum 1-year follow-up was conducted. Patient data on postoperative complications, including reoperation rates and proximal junctional kyphosis (PJK), and radiographical parameters was collected and statistically analyzed. Results: With mean follow-up of 21.1 months, the overall reoperation rate was significantly lower in the S2AI group than in the IS group (21.7% vs 58.8%, P = .01), but the incidence of PJK was similar (32.6% vs 35.3%, P > .99). Moreover, the time to reoperation in the IS group was significantly shorter than in the S2AI group (P = .001), and the S2AI group trended toward a longer time to reoperation due to PJK (P = .08). There was a significantly higher change in pelvic incidence (PI) in the S2AI group (−6.0°) compared with the IS group (P = .001). Conclusions: Compared with the IS technique, the S2AI technique demonstrated a lower rate of overall reoperation, a similar rate of PJK, longer time to reoperation, and possible reduction in PI. Future studies may be warranted to clarify the mechanism of these results and how they can be translated into improved patient care.

The Effects of High-Dose Parathyroid Hormone Treatment on Fusion Outcomes in a Rabbit Model of Posterolateral Lumbar Spinal Fusion Alone and in Combination with Bone Morphogenetic Protein 2 Treatment

BACKGROUND Parathyroid hormone (PTH) (1-34) treatment reduces fracture risk in osteoporotic patients. Previously, we demonstrated in a rabbit model that low-dose PTH treatment resulted in increased fusion mass volume. As effects of PTH on bone are dose-dependent, we aimed to evaluate whether increasing dosage of PTH increases both volume and biomechanical stiffness of the resulting fusion masses and/or exhibits synergistic effects with low-dose bone morphogenetic protein 2 (BMP-2). METHODS Posterolateral lumbar spinal fusion surgery was performed on 60 New Zealand White rabbits divided into 6 experimental groups: iliac crest autograft alone, autograft plus 20 μg/kg/day PTH, autograft plus 40 μg/kg/day PTH, BMP-2 alone, BMP-2 plus 20 μg/kg/day PTH, and BMP-2 plus 40 μg/kg PTH. Fusion was assessed at postoperative week 6 via manual palpation, volumetric computed tomography analysis, and 4-point bending biomechanical testing. RESULTS All groups treated with BMP-2 fused. Increasing doses of PTH resulted in increased fusion mass volume compared with autograft alone. Autograft plus 40 μg/kg/day PTH yielded fusion mass volumes comparable to BMP-2. When the autograft groups were considered alone, increased mechanical stiffness was observed only in the 20 μg/kg/day group. No significant stiffness differences were observed between BMP-2 groups. CONCLUSIONS Treatment with the highest dose of PTH resulted in fusion mass volumes similar to those obtained with BMP-2. When the autograft groups were considered alone, significant increases in mechanical stiffness were observed at a dosage of 20 μg/kg/day, suggesting there may be an optimal dose of PTH in the rabbit model. Effects of BMP-2 on fusion were dominant.

Effects of Single versus Hypofractionated Focused Radiation Therapy on Vertebral Structure and Biomechanical Integrity

Introduction Stereotactic radiosurgery has shown great promise in the treatment of metastatic lesions within the spine. However, recent clinical studies have indicated that the procedure may increase the risk of developing vertebral compression fractions, particularly in osteoporotic patients (Rose et al, 2009. J Clinical Onc. 27(29):5075; Boehling et al, 2012. J Neurosurg Spine. 16:379). There is thus a critical need for research examining the effects of focused radiation on bone quality and mechanical properties. We have developed a rabbit model which enables the analysis of the effects of focused radiation on vertebral osteonecrosis, structure, and biomechanical integrity. Using this model, we are testing the hypothesis that fractionation of radiation dosing can reduce radiation osteonecrosis and preserve structural and biomechanical integrity of the spine. Material and Methods The L5 vertebral body of New Zealand White (NZW) rabbits was treated, under computerized tomography (CT) guidance, with either a single 24 Gy dose of radiation or three fractionated doses over 3 consecutive days of 8 Gy radiation via the small animal radiation research platform (SARRP) (Wong et al, 2008. Int J Radiat Oncol Biol Phys. 71(5): 1591). Effects of radiation treatment on L2, L4, L5, and L6 vertebral osteonecrosis, structure, and biomechanical integrity were evaluated 6 months postirradiation via high-resolution CT imaging (Skyscan, Bruker, Belgium), histology, and nondestructive biomechanical compression testing and were compared with nonirradiated controls. Vertebral bone volume over total volume (BV/TV), trabecular thickness (Tb.Th.), and trabecular spacing (TB.Sp) were evaluated from CT images via CTAn software (Bruker, Belgium). Result/Conclusion: Results till date suggest that a localized single dose of 24 Gy radiation leads to loss of vertebral bone volume and trabecular number and a subsequent increase in trabecular spacing. Similarly, hypofractionation of the radiation dose (3 × 8 Gy) leads to reduced trabecular number and increased trabecular spacing, yet preserves normalized bone volume. Whether these changes in bone morphology translate into reduced mechanical integrity is currently under analysis. Future work will utilize this model to evaluate the efficacy of various therapies, such as teriparatide (PTH [1–34]), in the prevention of radiation-induced osteonecrosis.

A Quantitative Study of the Effects of High-Dose Parathyroid Hormone (1–34) and Low-Dose rhBMP-2 on Posterolateral Lumbar Spine Fusion in a Rabbit Model

Introduction Parathyroid hormone (1–34) (PTH), which is commonly used in the treatment of osteoporosis, has been shown to increase bone mass and reduce the risk of fracture. Previously, we demonstrated that, while intermittent low-dose (10 µg/kg) PTH (1–34) treatment resulted in increased fusion mass volume, it did not improve biomechanical stiffness over the use of autograft alone, and did not improve fusion when combined with BMP-2 treatment (Lina et al, Spine [Phila Pa 1976]. 2014; 39(5):347). However, studies in other rodent models have indicated that the effects of PTH (1–34) on spinal fusion may be dose-dependent (Ming et al, Spine [Phila. Pa. 1976]. 2012; 37(15): 1275; Abe et al, Bone. 2007; 41(5): 775). These rat and mouse studies used PTH (1–34) doses as high as 20 to 40 µg/kg compared with the 10 µg/kg used in our experiments. We thus aim to evaluate whether increasing the dose of PTH (1–34) administered increases both the volume and biomechanical stiffness of the resulting fusion masses and/or exhibits synergistic effects with low-dose BMP-2 treatment. Materials and Methods A total of 60 rabbits underwent posterolateral intertransverse process lumbar spinal fusion surgery, and were assigned to one of the six groups depending upon the fusion grafting group employed: iliac crest autograft alone (n = 10), iliac crest autograft + 20 µg/kg PTH (1–34) (n = 10), iliac crest autograft + 40 µg/kg PTH (1–34) (n = 10), rhBMP-2 alone (n = 10), rhBMP-2 + 20 µg/kg PTH (1–34) and, rhBMP-2 + 40 µg/kg PTH (1–34). Fusion mass and quality were assessed using manual palpation, CT analysis of fusion mass volume, and four-point nondestructive biomechanical testing. Results/Conclusions: Although manual palpation is used as the standard measure of fusion, we found that CT analysis proved more effective in differentiating fused masses based on bone formation, not fibrous tissue. Both the PTH (1–34) group and BMP-2 increased bone density and volume of the fusion masses. Biomechanical analysis of fusion mass strength is currently underway.