key: cord-1043683-nlk8pjv2
authors: Roberti, Fabio; Arsenault, Katie
title: Minimally invasive lumbar decompression and removal of symptomatic Heterotopic bone formation after spinal fusion with rhBMP-2
date: 2020-05-06
journal: World Neurosurg
DOI: 10.1016/j.wneu.2020.04.235
sha: 6ba26d7ab2a4ba248c1d7eff1357e41e1ba50f0b
doc_id: 1043683
cord_uid: nlk8pjv2

Abstract We present a case of symptomatic heterotopic bone formation following revision of posterolateral lumbar fusion/instrumentation and “off-label” use of recombinant human bone morphogenetic protein-2 (rhBMP-2), treated successfully with the use of a minimally invasive tubular approach.

The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) as an osteoinductive factor in spine surgery has been approved by the US Food and Drug Administration for singlelevel anterior lumbar fusion with tapered cages in skeletally mature patients (1) . Due to its proven effectiveness in increasing postoperative fusion rates (2, 3) , the "off-label" use of these proteins has gained wide spread popularity among spine surgeons dealing with various spinal conditions (4, 5, 6, 7, 8, 9) and a published review of Administrative data found that 85% of rhBMP-2 utilized in spinal surgery fell under the "off-label" definition (10) . Notwithstanding the proven benefits, several studies regarding complications associated with the use of rhBMP-2 have been so far published. Increased rates of infection, postoperative seromas and hematomas, delayed wound healing, dysphagia and neck swelling, retrograde ejaculation, symptomatic radiculitis, vertebral osteolysis, cage subsidence as well as heterotopic bone formation have all been reported following the use of rhBMP-2 in spine surgery (11, 12, 13, 14, 15, 16, 17, 18) . We report a case of symptomatic heterotopic bone formation following lumbar spinal revision surgery and posterolateral fusion with rhBMP-2, successfully treated using a minimally invasive tubular approach and provide documentation of the technical aspect of the procedure.

A 65-year-old obese female underwent an open lumbar laminectomy with instrumented allograft postero-lateral fusion using iliac bone graft, local bone, calcium phosphate augmentation and pedicle screws instrumentation at L4-L5 at an outside Institution, with clinical improvement. Three years after the initial surgery, she experienced recurrent low back pain and was diagnosed with pseudo-arthrosis and hardware failure (fractured left L5 pedicle screw) that prompted a revision surgery with fractured hardware removal and extension of the instrumented fusion to S1, bilaterally. At the time of the revision surgery rhBMP-2 was utilized "off-label" to promote a successful postoperative postero-lateral arthrodesis. Both initial and revision procedures were performed at the same hospital and by the same surgeon. Three years after the revision surgery she started experiencing recurrent episodes of severe L5 and S1 left radiculopathy and medical management and lumbar steroids injections failed to reduce the severity of the symptoms. This is when we first saw the patient. A clinical examination confirmed the presence of radicular signs and symptoms with no neurological deficits or significant back pain. Lumbar x-rays and CT scan were performed and revealed the presence of new broken hardware on the left side (fractured S1 pedicle screws) as well as significant heterotopic bone formation mainly involving the left L5-S1 lateral recess, leading to severe stenosis and nerve root compression (fig 1-2-3) . Despite the findings of broken hardware, there were no signs of mechanical instability at a flexion-extension x-ray and the CT documented the presence of a solid joint arthrodesis, especially on the right (fig 4-5-6a-6b ). An MRI was also performed which confirmed the diagnosis of severe lateral recess stenosis at L5-S1 due to heterotopic bone formation (fig 7) . Clinically she had only minimal axial low back pain, no radiological signs of mechanical instability, with most of the symptoms being radicular in nature. She was severely obese with a BMI of 40.10 with history of hyperlipedimia, HTN and CAD. After discussing the surgical options with the patient we elected to explore the fusion, remove the broken instrumentation and decompress the involved nerve roots by removing the heterotopic bone formation using a minimally invasive tubular approach. Open surgery with complete revision of instrumentation and redo arthrodesis was also discussed. In light of the absence of significant low back pain, the predominance of radicular symptoms, the absence of mechanical instability and the presence of bilateral facet arthrodesis, as well as the history of previous lumbar surgeries and associated medical comorbidities, we felt a minimally invasive approach was an appropriate option to be selected in this case and the patients concurred with this informed decision.

The patient was positioned on a standard prone position on a Wilson frame. METRx tubular system and antero-posterior (AP) and lateral intraoperative fluoroscopy guidance were utilized. A 3 cm incision was made over the AP x-ray projection of the L5-S1 broken screws on the left side and the fascia was open approx. 3-4 cm lateral to the midline, as guided by the x-rays. An Xtube expandable tubular retractor was utilized to expose the L5-S1 hardware. The rod was exposed and any surrounding newly formed bone was carefully drilled away. The rod was then cut using a carbide drill bit and removed. The lower broken screw (S1) was then utilized as landmark to start our microscopic dissection (fig 8) . The borders of the previous laminectomy were the identified, epidural scarring removed and the dura and nerve roots displaced by the presence of the heterotopic bone formation identified. The traversing nerve root was decompressed below the area involved by the ectopic bone formation and the exiting nerve root was isolated and decompressed above it (fig 9-10-11)

Once the nerve roots and the lateral dura were identified the heterotopic bone was removed by gentle drilling and use of Kerrison rongeurs until complete decompression was achieved ( fig 12) . After hemostasis was achieved and any dural leak ruled out, the remaining loosened hardware (S1 screw head that was kept in place as landmark) was removed. The Xtube was removed and the fascia and would closed using standard techniques. The procedure lasted approx. 90 minutes and blood loss was minimal (<50 cc). In light of the absence of significant low back or radiological signs of mechanical instability, the documented solid arthrodesis on the contralateral side, as well as the presence of retained fractured screws within the L5 and S1 pedicles, we elected not to place supplemental instrumentation. A postoperative CT confirmed good neural decompression (fig 13) and the patient was discharged home on postoperative day 1. The radicular symptoms resolved and no recurrent symptoms or complications were recorded at a 1-3 and 6 month follow up. At the most recent clinical follow up (7 years after the minimally invasive surgery) the patient still remains pain free without any significant recurrent radicular symptoms or axial back pain and has been able to resume recreational sport activities. In light of the ongoing Covid 19 pandemic and following Institutional protocols and policies while dealing with this event, long term follow up radiological examinations were not obtained.

Heterotopic (or ectopic) bone formation is a known complication associated with the of rhBMP-2 during spinal fusion surgery (19, 20, 21) and due to its possible compressive nature this condition may lead to recurrent or worsening symptoms in the postoperative period. Depending on size, symptoms and location of the ectopic bone formation surgical treatment may be needed, posing sometimes a technical challenge especially in patients who already underwent revision surgery of that carry multiple medical comorbidities. In such patients the use of minimally invasive decompressive techniques may be beneficial in tailoring the treatment to the symptomatic condition while minimizing possible adverse effects sometimes associated with open revision surgery. Minimally invasive spine surgery (MISS) techniques are nowadays utilized by many surgeons as an alternative or adjunct to open spine surgery in the treatment of various degenerative pathologies involving the cervical, thoracic and lumbosacral spine (22, 23, 24, 25) as well as trauma related and tumoral conditions (26, 27) . Centers and surgeons familiar with these novel techniques have also expanded the use and indications of this lesser invasive techniques to deformity correction surgery and revision surgery as well (28, 29, 30) . In our practice we too have expanded the use of MISS techniques as we live in a community were many patients are seen in consultation in their 7 th and 8 th decade of life. Spine surgery in the elderly may be at time challenging as multiple comorbidities, osteopenia/osteoporosis, as well as history of multiple previous spine surgeries need to be carefully considered while selecting the most effective and safe surgical (or non-surgical) approach. Revision spine surgery may also prove challenging as several factors may contribute to render some of these procedures more complicated than others. Lack or paucity of information related to previous surgeries, diagnostic limitation of radiological studies available (e.g. patients with spinal cord stimulators or non-MRI compatible implanted devices) and post-surgical anatomical changes and fibrosis do in fact play an important role during the preoperative and operative decision making process in such patients. Anatomical landmarks may difficult to recognize during revision surgery as post-operative changes, associated deformity and epidural fibrosis may all render the surgeon's evaluation of the operative field at times challenging. This is especially true in MISS where the anatomical exposure is usually limited to the surgical area of interest and in such cases an optimal use of preoperative and intraoperative imaging plays a very important role in facilitating the surgeon during the various steps of the selected approach. MISS offer many benefits in this cohort of patients (elderly, revision surgery, multiple comorbidities) as limited tissue dissection, minimal blood loss, shorter surgery time, faster and easier mobilization, lesser and shorter need for postoperative narcotics are all in favor of the use of such techniques when deemed feasible and appropriate. In the presented case it is unclear when the hardware failed/re-fractured as the patient did not complain of significant low back pain at the time of our initial evaluation. It is indeed possible that the hardware failure happened before the arthrodesis was complete and solid and before the ectopic bone formation became symptomatic. Also we were unable to directly confirm what dose of rhBMP-2 was utilized at the time of the revision surgery, therefore cannot comment on this specific issue as cofactor for the onset of the heterotopic bone formation. Review of previous operative reports revealed that the initial postero-lateral fusion was performed with the use of iliac crest and local bone autograft as well as calcium phosphate allograft augmentation. In light of the recurrence of radicular symptoms and evidence of fractured hardware at L5, the patient underwent a revision surgery with "exploration of fusion, removal of L5 instrumentation, bilateral transverse process fusion with local bone graft and "off label" use of BMP", as well as left TLIF at L5-S1 with PEEK allograft and L4-S1 bilateral pedicle screw instrumentation.". According to the operative report there was no presence of heterotopic bone formation at L5-S1 at that time of the revision surgery and the BMP sponges were "morcellized and placed in smaller pieces, combined with the local bone graft, into both posterolateral gutters". The amount of BMP utilized was not recorded. The colleague also commented that the "fixation of the L5 screw on the left side was extremely good and had sustained a fatigue fracture at its base, indicating a solid anchorage in the L5 pedicle" Therefore such fractured screw was not retrieved at that time. In light of the documented absence of heterotopic bone formation at the time of the revision surgery, the addition of calcium phosphonate to promote the arthrodesis during the initial lumbar fusion does not appear to have played a role in the genesis of the ectopic bone formation in this case, and it appears that this condition is to be associated to the use of rhBMP-2, as previously described (11) . In the presented case an open procedure of revision/decompression/lysis of adhesions could have certainly been utilized but in light of the patient's expectations, the absence of significant low back pain and radiological instability, as well as the presence of numerous medical comorbidities, we chose a minimally invasive approach, which proved to be successful in providing a long lasting relief of the preoperative symptoms. Although the treatment of heterotopic bone formation associate with the use of rhBMP-2 may be challenging, the use of a minimally invasive tubular decompression may facilitate a tailored and safe approach to this condition and should be kept in the armamentarium of spine surgeons, as one of the many valid techniques to be considered and discussed with these patients.

In the presented case we found the use of minimally invasive techniques to be of benefit for the removal of heterotopic bone formation following lumbar spine fusion with rhBMP-2. This approach remains consistent with the concept that minimally invasive surgery should not equal lesser effective surgery and that final recommendation on the technique to be adopted should be tailored on a case-by-case scenario, keeping in mind patient's expectations, safety issues and goals to be achieved. 

Anterior lumbar interbody fusion using rhBMP-2 with tapered interbody cages

Is INFUSE bone graft superior to autograft bone? An integrated analysis of clinical trials using the LT-CAGE lumbar tapered fusion device

Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 16: bone graft extenders and substitutes as an adjunct for lumbar fusion

Fusion Rates of Lateral Lumbar Interbody Fusion Using Recombinant Human Bone Morphogenetic Protein

Radiographic and CT Evaluation of Recombinant Human Bone Morphogenetic Protein-2-assisted Cervical Spinal Interbody Fusion.Clin Spine Surg

Minimally invasive reduction of thoracolumbar burst fracture using monoaxial percutaneous pedicle screws: Surgical technique and report of radiological outcome

The MISDEF2 algorithm: an updated algorithm for patient selection in minimally invasive deformity surgery

Minimally invasive removal or revision of lumbar spinal fixation

Use of recombinant human bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans: a prospective, randomized clinical pilot trial: 2002 Volvo Award in clinical studies

Off-label use of bone morphogenetic proteins in the United States using administrative data

Complications associated with the use of the recombinant human bone morphogenetic proteins for posterior interbody fusions of the lumbar spine

Fineberg SJ et al Clinical sequelae after rhBMP-2 use in a minimally invasive transforaminal lumbar interbody fusion

Complications with the use of bone morphogenetic protein 2 (BMP-2) in spine surgery

Symptomatic ectopic bone formation after off-label use of recombinant human bone morphogenetic protein-2 in transforaminal lumbar interbody fusion

Intraoperative Computed Tomography Navigational Assistance for Transforaminal Endoscopic Decompression of Heterotopic Foraminal Bone Formation After Oblique Lumbar Interbody Fusion

Bone Morphogenetic Protein Usage in Anterior Lumbar Interbody Fusion: What Else Can Go Wrong? World Neurosurg

Complications Associated With Bone Morphogenetic Protein in the Lumbar Spine

Promoting fusion in minimally invasive lumbar interbody stabilization with low-dose bone morphogenic protein-2--but what is the cost?

Heterotopic ossification associated with recombinant human bone morphogenetic protein-2 (infuse) in posterolateral lumbar spine fusion: a case report.Spine (Phila Pa 1976)

Ectopic bone formation in titanium mesh loaded with bone morphogenetic protein and coated with calcium phosphate

Pseudo-Pedicle Heterotopic Ossification From Use of Recombinant Human Bone Morphogenetic Protein 2 (rhBMP-2) in Transforaminal Lumbar Interbody Fusion Cages

Clinical outcomes after minimal-access surgery for recurrent lumbar disc herniation. Neurosurg Focus

Minimally invasive transforaminal lumbar interbody fusion: one surgeon's learning curve

Removal of ossified ligamentum flavum via a minimally invasive surgical approach

The Use of a "Double-Triple Barrel" Technique during Minimally Invasive Multilevel Tubular Laminectomy. A Technical Note

Comparison of transforaminal lumbar interbody fusion outcomes in patients receiving rhBMP-2 versus autograft

Minimally invasive resection of spinal hemangioblastoma: feasibility and clinical results in a series of 18 patients

Correction of marked sagittal deformity with circumferential minimally invasive surgery using oblique lateral interbody fusion in adult spinal deformity

Bone morphogenetic protein in adult spinal deformity surgery: a meta-analysis

Bone Morphogenetic Proteins in Anterior Cervical Fusion: A Systematic Review and Meta-Analysis. World Neurosurg

rhBMP-2 (recombinant human bone morphogenetic protein-2) Fabio Roberti: Conceptualization, Methodology, Writing-Original draft preparation, Validation, Writing-Reviewing and Editing.