Fusion Rates of Patients Treated with rhBMP-2 (Infuse) in Primary Multilevel Posterolateral Lumbar Fusion Surgery

Michael Rivlin; Marjorie M. Mariller, MD, MPH; Chan Roonprapunt, MD, PhD; Catherine N. Petchprapa, MD; Kevin

Math, MD; Fabien D. Bitan, MD; Andrew M. Casden, MD; Michael G. Neuwirth, MD; Paul Kuflik, MD, FAAOS

The Spine Institute of New Yorkat Beth Israel Medical Center

Presented at IMAST 13th Annual Scientific Meeting

Background• Spinal orthopedic surgery often requires the fusion of

multiple vertebrae in order to ensure fixation of the axial spine.

• Indication of spinal fusion or arthrodesis are:– cases that have increased axial instability or deformity that

has a high probability of progressing.– degenerative disorders of the spine– curvature deformity– vertebral fractures– herniated nucleus pulposus– Spondylolisthesis– pseudoarthroses

Background• Fusion can be achieved using different grafts and

devices i.e.– autologous grafts harvested from the patients iliac crests– allografts, synthetic materials that enhance bone growth

(often complemented with instrumentation to insure stability)

• The rates of fusion following an instrumented posterolateral fusion with autograft vary from 43% to 83% and from 66% to 75% for 2-level fusions and 3-level fusions, respectively.

Objective

• To determine the fusion rate of patients treated with BMP undergoing multilevel posterolateral lumbar fusions.

Materials• Bone Morphogenetic Proteins (BMP) are

cytokines that belong to a family of TGF-beta superproteins. There are 15 BMPs identified (BMP-2 is used in the present study).

• BMP functions include:– the induction of bone and cartilage formation due to

which they were named after – maturation of osteocytes, chondroblasts, osteoblasts– implicated in the process of angiogenesis in bone

Materials• Recombinant techniques have enabled

scientists to purify BMP (rhBMP) free from potentially infectious materials

• It is packaged in a collagen (type I) sponge containing rhBMP and it is often applied with fusion cage systems.

• Preparation of the implant is performed intraoperatively by combining the BMP infused collagen sponge and the Mastergraft.

Materials

Mastergraft addedMastergraft added

Radiograph of the prepared implant

Implant to be usedImplant to be used Rolled into shapeRolled into shape

BMP infused collagen spongeBMP infused collagen sponge

Methods• In a retrospective review of patients operated at

the Spine Institute, we identified 28 patients who had undergone primary two- or three level lumbar fusion with rhBMP-2 for degenerative conditions, such as stenosis, spondylolisthesis, and degenerative disc disease.

• The cases of tumor, infection, or trauma were excluded.

• No patients had iliac bone crest harvested.• The patients were retrospectively followed up at 3,

6, 12 and when available, 24 months.

Methods

Methods• The diagnosis of pseudarthrosis was determined by

plain X-rays and scored by independent radiologists using the posterior fusion grading system developed by Lenke et al.

• Fusion was graded on a scale of 1 to 4 Levels - grade 1 or 2 were considered as fused.

• Fusion was achieved by placing BMP graft over the lateral recess of the exposed and decompressed (laminectomy) spine. The graft was placed over the decorticated bleeding bone.

Grade 1: Bilateral solid fusion

Grade 2: Unilateralsolid fusion, partial fusion contralaterally

Grade 3: Partialgraft resorption with no clear fusion

Grade 4: Bilateralgraft resorption with no evidence of fusion

MethodsRadiographic Criteria for Fusion

Results

Descriptive data• 68% of the patients included in the study

were women. The patients’ mean age was 61 years old (range 33-80). The degenerative conditions that were treated included lumbar stenosis (79%), spondylolisthesis (71%) and degenerative disc disease (32%).

ResultsStatistics of Patients # of Pts %

Smoking 3 11%

Osteopenia 5 21%

Diabetes 2 7%

Regular alcohol users 11 39%

Preoperative NSAIDS 19 68%

Preoperative narcotics 12 43%

Prior spine surgery 2 7%

Neurological symptoms 6 22%

Functional defects 1 4%

Physical therapy 14 54%

Worker’s compensation 4 17%

Results

BMI # of Pts. %

Normal 7 25%

Overweight 11 39%

Obese 9 32%

Morbidly obese 1 4%

ResultsSurgical data• All twenty eight patients had undergone a

decompressive laminectomy, and instrumented posterolateral fusion with BMP placement.

• The average amount of BMP placed was 9.4 micrograms per levels fused.

• Twenty-five patients underwent a 2-level fusion and three patients underwent a 3-level fusion.

• Local bone was used in half of the patients.

ResultsOutcomes # of Pts Mean (95% CI)

Length of surgery (hh:mm) 28 4:10 (3:52-4:28)

EBL (ml) 27 637 (527-747)

Cell saver (ml) 28 114 (71-157)

Hospital stay (days)* 27 6.55 (5.84-7.26)

Complications # of Pts

Infection, return to OR 2

Infection 2

DVT 1

ResultsTransfusion• Two out of the 28 patients received a blood transfusion

(they received one and two units of blood, respectively).

Risk factors• Preoperative narcotic use was associated with lower

fusion rates (p=0.002); all patients without previous narcotic use had a solid fusion. There was no association between the fusion rate and the following factors: smoking (p=0.107); preOp NSAIDS (p=0.630); BMI (p= 0.232); and regular consumption of alcohol (p=0.174).

Results

Fusion rate• The fusion rate per level was 83% at last

follow-up (mean follow- up period was 12 months). Seventy nine percent of the patients achieved fusion at all levels. Half of the failures achieved partial fusion.

ResultsOverall Fusion Rate (per level)

Conclusions• Fusion rates of patients treated with rhBMP-2 in

primary multilevel posterolateral lumbar surgery were similar to historic fusion rates reported for multilevel instrumented arthrodesis using autogenous bone graft. Therefore, rhBMP-2 represents a good option for obtaining successful multilevel lumbar arthrodesis without the associated historical graft site morbidity.

Conclusions• As a future investigation, we plan:

– To measure the clinical and radiological outcomes of BMP fusion for different surgical approaches (posterior, anterior, lateral, etc)

– To focus also on the risk factors as confounders, such as the effect of smoking and NSAIDs, to observe the effect these play on the outcomes.