Abstract

Background: Classically, the iliac crest bone graft (ICBG) was the gold standard in lumbar fusion surgeries. There have been recent studies to evaluate other surgical techniques and modalities that considerably lower the rates of morbidity attributed to autologous bone graft harvesting. Objective: The purpose of this study is to evaluate the clinical suitability of combining recombinant human bone morphogenic protein-2 (rhBMP-2) to bioresorbable implants as interbody spacers via the minimally invasive posterior lumbar interbody fusion (PLIF) technique. Study Design: This is a retrospective study of forty consecutive patients who underwent the minimally invasive PLIF procedure after treatment with rhBMP-2 added to bioresorbable implants with at least two years of follow-up. Methods: This study assessed the use of combining rhBMP-2 to bioresorbable implants in forty consecutive patients via minimally invasive PLIF. Results: At the nine month postoperative follow-up, thirty eight patients (95%) were found to have solid fusions. Independent neuroradialogists' evaluations of x-ray films and CT scans with 2-D reconstructions were obtained at 3, 6, 9, 12, and 24 months respectively. Conclusions: The minimally invasive PLIF technique described herein utilizing bioresorbable implants in conjunction with rhBMP-2 can achieve successful lumbar fusion safely and effectively.

Abbreviations

ALIF: Anterior lumbar interbody fusion AP: Anteroposterior CT: Computed tomography Cc(s): Cubic centimeter(s) EBL: Estimated blood loss HNP: Herniated nucleus pulposis PLa: Polylactide PLIF: Posterior lumbar interbody fusion PSF: Posterior segmental fixation rhBMP-2: Recombinant human bone morphogenic protein-2 TLIF: Transforaminal interbody fusion

Introduction

Posterior lumbar interbody fusion (PLIF) is an effective treatment option for patients with symptomatic degenerative disc disease, spondylolisthesis and other painful lumbar spinal pathologies that have failed conservative medical treatment modalities. Fusion of the pathologically unstable lumbar spine segment can offer significant relief from this often progressive and debilitating medical condition. 6,12,24,31,33,43 Arthrodesis, i.e. fusion may be achieved with the classic open PLIF that many spinal surgeons are accustomed to. However, this open technique has been criticized for excessive muscle dissection and neural retraction. Posterior lumbar decompression and PLIF can now be readily performed through tubular retractors via one-inch incisions without significant paraspinal muscle dissection. Posterior segmental fixation (PSF) can be achieved in an essentially percutaneous manner via the same incision. The minimally invasive PLIF technique described herein limits the extent of posterolateral soft tissue exposure, muscle stripping and injury; ultimately achieving successful 360° fusion via a bilateral dorsal surgical approach. The spinal surgeon uses the traditional posterior approach to gain access to the lumbar spine; however, surgical dissection is limited laterally to the facet joints. 24 Through this surgical approach, direct neural decompression can be accomplished, proper disc space height and sagittal balance can be restored 6,24,31,33,41,43 and intervertebral grafts can be placed in a biomechanically advantageous position. 24

This present study analyzed the clinical and radiographic results in 40 cases of 360° lumbar fusion performed with minimally invasive PLIF surgical technique and after treatment with rhBMP-2 added to 70:30 poly (L-lactide-co-D, L-lactide) bioresorbable implants as interbody spacers in single and multi-level applications for various lumbar spine pathologies. The promising results obtained by Lanman and Hopkins' pilot study of 360° lumbar fusion via the TLIF technique after treatment with rhBMP-2 added to 70:30 poly (L-lactide-co-D, L-lactide) bioresorbable implants, 32 can also be achieved safely and effectively via the minimally invasive PLIF technique described herein.

Materials and Methods

Patient Population: Retrospective data were collected on forty consecutive patients who underwent the minimally invasive PLIF procedure after treatment with rhBMP-2 added to bioresorbable implants between 01-28-2004 and 01-28-2005. The 40 consecutive patients (24 males, 60.0% and 16 females, 40.0%) with a mean age of 58.2 years underwent the PLIF procedure at a total of 42 pathological levels fused for a variety of lumbar conditions such as: spondylolisthesis, degenerative disc disease, and herniated nucleus pulposis (disc disruption). Nine patients (22.5%) had Grade 1 (< 25% slippage) spondylolisthesis alone, three patients (7.5%) had Grade 2 (>25-50% slippage) spondylolisthesis alone, one patient (2.5%) had degenerative disc disease alone, and ten patients (25%) had disc disruptions alone. Sixteen patients (40.0%) had simultaneous Grade 1 spondylolisthesis with disc disruptions. One patient (2.5%) had simultaneous Grade 2 spondylolisthesis with a disc disruption. Overall, twenty patients had lumbar spine pathologies at L4-L5 alone, eighteen patients had lumbar spine pathologies at L5-S1 alone, and two patients had multi-level pathologies at L3-L4 and L4-L5 which were all successfully fused.

All of the forty patients (100%) had severe axial lower back pain as their presenting chief complaint, with 28 patients (70%) reporting simultaneous radicular pain for at least 6 months in duration that had not responded to conservative, non-operative treatment. The preoperative diagnosis for each of the patients along with sex, age, level(s) fused, operating time, estimated blood loss, length of hospital stay postoperatively, and fusion time in months is illustrated in Table 1.

Table 1: “The forty consecutive patients who underwent the minimally invasive posterior lumbar interbody fusion (PLIF) procedure after treatment with recombinant human bone morphogenic protein-2 (rhBMP-2; INFUSE® Bone Graft) added to 70:30 poly (L-lactide-co-D, L-lactide) (HYDROSORB® TELAMON®) bioresorbable implants as interbody spacers.”

Abbreviations used in Table 1:

DD: Disruption of Disc (i.e. Herniated Nucleus Pulposis) DDD: Degenerative Disc Disease EBL: Estimated Blood Loss F: Female L: Lumbar level M: Male Min: Minutes OR: Operating Room Post-op: Post-operative S: Sacral level Spondy: Spondylolisthesis

The majority (98.0%, or 38 patients) underwent a one-level fusion, and 2.0%, or 2 patients underwent two levels of fusion. The mean estimated blood loss was 44.0 cc(s) with a range of 30.0 to 100.0 cc(s). The mean operating time was 2.6 hours with a range of 2.0 to 4.2 hours and the mean post-operative hospital stay was 4.1 days with a range of 3 to 6 days.

The 40 patients were consecutively selected from the four neurosurgeons' case loads (M.C.O., M.B.E., M.E.L., and P.H.H.) All patients who underwent the procedure were operated at North Shore University Hospital, Manhasset, NY. The inclusion criterion for patient selection in this study was that the patients complained of symptomatic back pain for at least 6 months or more in duration that did not respond to nonoperative treatments and whom ultimately underwent the minimally invasive PLIF procedure after treatment with recombinant human bone morphogenic protein-2 (rhBMP-2; INFUSE® Bone Graft; distributed by Medtronic Sofamor Danek USA, Inc.) added to poly (L-lactide-co-D, L-lactide) (HYDROSORB® TELAMON®; distributed by Medtronic Sofamor Danek USA, Inc.) bioresorbable implants to alleviate symptomatology. Additionally, all patients needed to demonstrate pathological spine segment instability which required fusion via flexion/extension X-rays, static CTs and MRIs. Exclusion criteria for this study were a previous attempt at fusion at the intended surgical level, autoimmune disease, malignancy, pregnancy, and significant osteoporosis.

Surgical Technique: The operations were performed by one or two surgeons while the patient was under general anesthesia. The patient was positioned prone on padded bolsters with the both arms forward. An operating room table which allowed C-arm fluoroscopy in both AP and lateral directions from L3 to S1 was utilized. Two one-inch paraspinal incisions were made on either side, 2 to 2.5 centimeters off the midline at the appropriate intraoperative disc level. The positioning was then confirmed via lateral fluoroscopy intraoperatively. The specific location of each incision is made directly above the facet complex or interpedicular space. This also allowed for parallel instrumentation of the corresponding disc space. The degree of lordosis was taken into account and was corrected for in each patient. After opening the skin and lumbosacral fascia, a series of dilators were used beginning with a K-wire and ending with a 22-26 mm working port which was secured to a self-retaining retractor arm fixed to the operating room table. When the need arose, removal of the soft tissue around the hypertrophied facet and lateral lamina was performed in order to proceed with the drilling of the facet and the lower edge of the upper lamina. A complete facetectomy via METRx® (METRx® System incorporates technology developed by Gary K. Michelson, M.D.; distributed by Medtronic Sofamor Danek USA, Inc.) microsurgical system tubes was performed in all cases to effect adequate nerve root decompression and/or to minimize thecal retraction. Disc removal was followed by sequential disc space distraction by alternating increasing sized distractors from one side to the other. Optimum distraction was determined by a combination of preoperative disc space height measurement and intraoperative distractor tightness. Once optimum distraction was accomplished on one side, a box cutting chisel was tamped on the other corresponding side, usually to a depth of 30-35 mms. A medium absorbable collagen sponge (2.5cm x 5cm) was cut into thirds after being initially loaded with rhBMP-2. One sheet was then stuffed into the center of each bioresorbable implant, and the final sheet was placed anteriorly in the disc space, prior to the placement of the second implant. The bioresorbable implant could then be tamped into place with at least 5 mms of countersinking; a similar procedure was done on each side. If two surgeons were available, simultaneous PLIFs could be performed through dualing tubes. The tubular retractors were removed after thorough irrigation with antibiotic solution.

Posterior segmental fixation was performed using the CD HORIZON® SEXTANT ^TM rod insertion system (distributed by Medtronic Sofamor Danek USA, Inc.). The pedicles were traversed with Jamshidi needles followed by long K-wires. Next, a cannulated tap was placed over the K-wires and the pedicles tapped. A multi-axial cannulated M-8 titanium screw attached to a screw extender was then placed through the pedicle into the vertebral body. After matching the male and female ends of the screw extenders, the CD HORIZON® SEXTANT ^TM arc was attached. A small incision placed superiorly on each side allowed initial trocar passage through to the upper screw head. At this point calipers were attached to determine proper rod length. A pre-bent, pre-cut 5.5mm titanium rod of the appropriate length was secured to the CD HORIZON® SEXTANT ^TM arc and passed percutaneously through the heads of the screws. Locking nuts in the screw extenders were tightened with gentle compression. The screw extenders and CD HORIZON® SEXTANT ^TM arc were disengaged and the wounds closed.

Assessment of Results

Patients were assessed preoperatively, during their hospitalization, and postoperatively at 2 weeks, 3, 6, 9, 12, and 24 months respectively. The clinical outcomes were measured using a modified Functional Economic Outcome Rating Scale of PROLO (Table 2) at the time of follow-up.

Table 2: “Modified Functional Economic Outcome Rating Scale of PROLO used to assess clinical outcomes.”

Abbreviations used in Table 2:

NSAIDs: Non-steroidal anti-inflammatory drugs

Independent neuroradialogists' evaluations of x-ray films and computed tomography scans with 2-D reconstructions were obtained at 3, 6, 9, 12 and 24 months respectively to determine trabecular bone growth (i.e. fusion) within the operative disc space.

Results

One-level fusions were performed on 38 patients, and two-level fusions were performed on 2 patients. The mean postoperative hospital stay was 4.1 days with a range of 3 to 6 days. The mean fusion time observed via CT scan in this report was 6.2 months with a range of 3 to 12 months. At the three month postoperative follow-up, eleven patients (27.5%) displayed successful trabecular bone growth (bridging of bone) within the operative disc space via CT scans (Figs. 1a and 1b).

Figure 1: Coronal (1a) and Sagittal (1b) CTs of patient #4 from Table 1 demonstrating successful trabecular bone growth, i.e. fusion (arrows) within the operative disc space of L5-S1 at three months postoperatively.

At the six month post-operative follow-up, 28 patients (70.0%) displayed successful trabecular bone growth within the operative disc space via CT scans, including 1 patient who underwent two levels of fusion. At the nine month postoperative follow-up, 38 patients (95.0%) displayed successful trabecular bone growth within the operative disc space via CT scans, including the second patient who underwent two levels of fusion (40 lumbar levels fused). At the 12 and 24 month postoperative follow-up, all patients (100.0%) displayed successful interbody fusions via CT scans (42 total lumbar levels fused).

The mean preoperative PROLO scale score for all (40) patients was 9 with a range of 7 to 11. The mean postoperative PROLO scale score used to measure clinical outcomes was 16 with a range of 12 to 19 at two years follow-up. Twenty-two patients reported good to excellent clinical outcomes (PROLO scale score of 16-20) and eighteen patients reported fair clinical outcomes (PROLO scale score of 12-15) at 2 years. Significant clinical improvement was seen from initial mean PROLO scale score of 9 to the mean postoperative PROLO scale score of 16 at two years. In the 40 patients who underwent the minimally invasive PLIF procedure in this study, no permanent neurological complications, wound infections, or construct alignment changes were observed as of to date.

Discussion

The PLIF procedure has been extensively utilized in this present report for the treatment of various dynamically unstable spinal pathologies such as spondylolisthesis (Grades 1 and 2), HNP or disc disruptions, and degenerative disc disease which require lumbar fusion. The minimally invasive technique described thus far, employs a bilateral dorsal approach to achieve 360° lumbar arthrodesis. The PLIF procedure offers simultaneous decompression of neural elements and the correction of abnormalities in alignment of sagittal balance of the spine. The high arthrodesis rates observed after PLIF can be attributed to a large fusion area, ample blood supply at the intraoperative disc space, and the ability to place the interbody graft under direct force. 25

The minimally invasive PLIF technique described herein offers distinct advantages over conventional open lumbar fusion surgery. One major advantage is less iatrogenic soft tissue damage which can have significant postoperative complications. In the traditional open approach, permanent muscle injury occurs as a result of direct muscle stripping and substantial muscle retraction during access to the pathological spine level. 23,28,29,37,47,49 Sihvonen et al concluded that the development of failed-back surgery could be a direct result of disrupted back muscle innervation and loss of muscular support. 47 On the other hand, minimally invasive PLIF technique is believed to yield decreased EBL, operative times, decreased hospital stays and overall improvement in the patient's quality of life. 19,20,25,26 The purpose and goal of minimally invasive PLIF technique is to achieve the same surgical objectives as the traditional open PLIF technique through a less traumatic approach. 25

One of the most common postoperative complications of PLIF as previously stated has been neurological injury secondary to neural manipulation and retraction. 43 Other complications of PLIF are cerebrospinal fluid leaks, deep tissue infections, and reoperations. The previous incidences of reported major surgical complication rates have ranged from 1 to 6.7%. 9,13,17,39,40 Deep wound infections at the site of surgery has been previously described to range from 1 to 4% and neurological injury has ranged from 1.7 to 6.5%, repectively. 9,13,17,18,21,22,27,39,40,44,45 The current incidence of neurological complications is substantially lower than reported in the 1980s and 1990s and can be attributed to better surgical technique and advanced surgical instrumentation. 9,13,17,18,21,22,27,39,40,44,45,48 The current movement in PLIF surgery is to limit neural element retraction through the use of a transforaminal interbody fusion (TLIF) surgical technique. 24 However, in the 40 patients who underwent the PLIF procedure in our study, no permanent neurological complications, wound infections, or construct and alignment changes were observed.

Since Cloward introduced the PLIF technique in the 1950s for ruptured vertebral discs, 12 he encountered a dilemma. That being, what to introduce into the intraoperative disc space to further increase the likely hood of successful, efficient interbody fusion? Cloward initially performed a wide laminectomy and facetectomies for adequate decompression and placement of bone grafts in the intraoperative disc space. 24 Many advancements have been made to the original PLIF by Lin et al 33 via intervertebral grafting of structural grafts and then by Kuslich et al 31 and Ray 43 with the advent of threaded interbody fusion cages as a modality for stabilization of the pathological lumbar segment. As advancements in lumbar spine surgery progressed, autologous bone grafting from iliac crest harvesting came into favor as the gold standard. Although adequate rates of arthrodesis were achieved, this latter modality introduced additional postoperative complications and increased morbidities. 24,32

Interestingly, Dimar et al 18 reported a 73.3% (45 patients) fusion rate at 2 years postoperatively when iliac crest bone grafts were utilized in single-level instrumented posterolateral fusions. However, Haid et al 24 also reported a 77.8% (33 patients) fusion rate at 2 years post-operatively when iliac crest bone grafts were performed in single-level degenerative lumbar disc disease with a PLIF, using stand-alone cylindrical threaded titanium fusion cages. R.W. Haid et al 24 stated at two years postsurgically, 13.3% of their patients displayed discomfort at the iliac crest graft site. Additionally, Dimar et al 16 also stated persistent hip pain at two years postoperatively in their patients who underwent iliac crest bone graft harvesting.

Two new recent advances in lumbar spine surgery will be discussed further. Firstly, significant technological advancements in interbody spacer materials have come a long way since their metallic counterparts' inception by Bagby in the 1970s for equine spinal instability. 14 The spinal surgery community has seen the evolution of interbody spacer designs change from rectangular, cylindrical, ring, and ultimately threaded geometries. 1,15,26,43 These interbody spacers were usually packed with morsalized autologous bone chips to enhance rates of arthrodesis 32 and ultimately inserted via PLIF, ALIF, or TLIF procedures. 32,42,43,52 Some of the drawbacks of metallic implants reported during numerous clinical studies were but not limited to: stress shielding and implant settling secondary to excessive implant stiffness and rigidity, 32,36,38 radiographic scatter and distortion when arthrodesis was to be aevaluated, 32 and permanent foreign body presence. 51 Furthermore, additional postoperative morbidity (i.e. persistent hip pain) was also encountered when autologous bone from the iliac crest was harvested, as previously discussed. 24,32

Synthetic bioresorbable polymers, particularly of the polylactide (PLa) variety have come under recent evaluation for use in lumbar spine interbody spacer applications. These bioresorbable polymers have been used by surgeons for over thirty five years 30 and are noted to have no long term foreign body presence 51 for they are known to biodegrade into H₂O and CO₂ over a reported period of 18-36 months. 11 This feature may offer superior bone to bone interface between corresponding superior and inferior vertebral endplates, reducing time to successful interbody fusion. An obvious benefit of the bioresorbable interbody spacer is that they have been shown to have less radiographic scatter than their traditional metallic interbody spacer counterparts, allowing for more accurate radiographic evaluations of fusion. 51

Clinically, Lowe et al 34 reported on 60 patients who underwent TLIF procedure and experienced no adverse events or complications at up to 9 months post-operatively. Secondly, Alexander et al 2 also reported successful use of PLa implants via PLIF in 15 patients and found comparable results to that of the Lowe et al study at one-year post-operatively. Thirdly, Austin et al 3 reported on an additional 12 patients who underwent PLIF with at least one-year of follow-up in whom successful clinical and neuroimaging results were demonstrated at 12 to 18 months post-surgery. 32 Finally, Coe and Vaccaro reported on 27 patients who underwent instrumented TLIF procedures using bioresorbable implants (70:30 poly (L-lactide-co-D, L-lactide)) added to iliac crest autografts and found that 25 patients (92.6%) had solid fusions at a mean of 31.9 months of follow-up. 10

Secondly, the use of rhBMP-2 has been shown in recent studies to initiate osteoinduction and to achieve earlier rates of spinal arthrodesis in both animal and human models, 4,5,32,35,50,53 not to mention an eventual decrease in morbidity when used in place of iliac crest harvesting. Van Dijk et al reported that rhBMP-2 appears to be well suited for use in combination with resorbable polymer interbody implants in goats. 52 Prospective randomized human clinical studies have reported equal arthrodesis rates and clinical outcomes with rhBMP-2 and a collagen sponge versus autograft when using either cortical bone dowels or threaded interbody cages where implanted via anterior lumbar surgical techniques. 7,8 To date, there has been only one other study that has evaluated the use of bioresorbable devices combined with rhBMP-2 in lumbar spine surgery for one or more levels. Lanman and Hopkins provided the first evidence of the feasibility of using bioresorbable implants in combination with rhBMP-2 for lumbar spinal fusion in 43 patients. 36 They reported successful fusion in 41 patients (98%) at 6 months postoperatively, for a total of 57 lumbar levels fused. We reported successful fusion in 38 patients (95%) at 9 months postoperatively, for a total of 40 lumbar levels fused.

Conclusions

The minimally invasive PLIF procedure utilizing 70:30 poly(L-lactide-co-D, L-lactide) bioresorbable implants in conjunction with rhBMP-2 can achieve successful lumbar fusion for a variety of common pathologies safely, effectively, and with reduced morbidity. Furthermore, the initial results of Lanman and Hopkins' pilot study along with this present one are encouraging and may provide an alternative treatment for achieving lumbar arthrodesis. It is the opinion of this group that bioresorbable interbody spacers used in combination with rhBMP-2 allows for earlier fusions and decreased complications when compared to other studies where iliac crest bone autografts or metal cages were utilized. Finally, larger studies need to be initiated to determine the best long-term treatment option for patients with symptomatic lumbar spinal pathologies that require stabilization via fusion.

Correspondence to

Attn: Peter H. Hollis, M.D. North Shore-Long Island Jewish Health System Department of Neurosurgery 900 Northern Blvd., Suite 260 Great Neck, NY 11021 Phone: 1-(516)-773-7737 Fax: 1-(516)-773-7751 Email: PHollis@optonline.net

References