113SProceedings of the NASS 26th Annual Meeting / The Spine Journal 11 (2011) 1S–173S

PURPOSE: Thepurpose of this study is to compare the outcomeof PLIFand

PLF in a well-defined patient population of adult degenerative spondylolis-

thesis. We aim to determine whether the addition of an intervertebral cage

improves the clinical outcome and fusion rate of patients undergoingpostero-

lateral fusion after decompression for degenerative spondylolisthesis.

STUDY DESIGN/SETTING: A prospective study of two different fusion

techniques for the treatment of single level degenerative spondylolisthesis.

All patients had undergone a trial of nonoperative treatment for at least

three months before surgery. Nonoperative treatment included physical

therapy (passive modalities and aerobic exercise) and nonsteroidal anti-

inflammatory drugs, if tolerated. Patients were recommended for surgery

if they had failed nonoperative treatment and continued to have significant

pain and/or significant daily activity restrictions. All patients were noted

on plain radiographs to have a single-level degenerative lumbar spondylo-

listhesis, and imaging studies (CT and/or MRI) demonstrated spinal steno-

sis at the level of the spondylolistheis. No patients had undergone prior

lumbar spinal surgery.

PATIENT SAMPLE: 59 patients with degenerative spondylolisthesis were

divided into two groups. Group 1 comprised of 32 patients who underwent

decompression and posterolateral fusion (PLF). Group 2 comprised of 27 pa-

tients who underwent decompression and posterolateral interbody fusion

(PLIF) with cage insertion. Average age of patients was 66 years: 34 males

and 25 females.

OUTCOME MEASURES: 1. Pre- and post-operative lordotic angles.

2. SF12 physical andmental health scores. 3.Visual analogue scores for pain.

METHODS: A prospective study was carried out including 59 patients

with degenerative spondylolisthesis. Average age of patients was 66 years:

34 males and 25 females. Patients were divided into two treatment groups:

Group1–32 patients with PLF and Group 2–27 patients with PLIF with

cage. Minimum two years follow-up. Outcomes were assessed by measur-

ing pre- and post-operative lordotic angles. SF-12 physical and mental

health scores were recorded along with visual analogue scores for pain.

Complications were also recorded. Inclusion criteria for patients enrolled

included degenerative lumbar spondylolisthesis of all grades and levels,

low back pain with or without sciatica, severely limited functional ability

and no age restrictions. The exclusion criteria were previous spinal surgery,

psychiatric disorders, and drug or alcohol abuse. All patients enrolled in

the study had pre-operative MRI scans within 1 year prior to surgery to

confirm the diagnosis of degenerative lumbar spondylolisthesis with a de-

generative intervertebral disc at the level of the slip with/without associ-

ated nerve root compression. All surgical procedures were carried out by

a single surgeon.

RESULTS: In the PLF group the mean preoperative lordotic angle was

16.6 which increased to a mean of 22.7 at latest follow-up, which was a sig-

nificant increase (p5.008). In the PLIF group the mean preoperative lor-

dotic angle was 15.6 which increased to a mean of 21.2 at latest follow-

up, which was a significant increase (p5.025), (Figure1). There was

a non-significant difference (pO.05) in the change of lordotic angles be-

tween the two groups. There was a significant improvement (p!.05) in

the SF12 mental and physical health scores and VAS scores in both groups

from pre-operative levels, but there was a non-significant difference

(p!.05) between the two groups. Fusion in the PLIF group was achieved

in 21 out of the 27 patients at 2 years follow-up. The 6 patients who were

not fused radiologicallly did not have any clinical symptoms to warrant

further surgical intervention. In the PLF group 24 out of the 32 patients

achieved fusion at 2 years follow-up. The 8 patients who were not fused

radiologically did not have any clinical symptoms to warrant further surgi-

cal intervention.

CONCLUSIONS: The current prospective study compared the clinical

and radiological outcomes of PLIF and PLF in the treatment of degenera-

tive spondylolisthesis with a follow-up of two years. We found similar

clinical outcomes in both study groups. The fusion rates and degree of cor-

rection of the lumbar lordosis were also similar in the two groups. Com-

plications were seen in both study groups with greater number of dural

tears in the PLIF group and on episode of implant failure in the PLF group.

We have found the use of a cage to achieve lumbar interbody fusion in the

treatment of degenerative lumbar spondylolisthesis does not confer any

All referenced figures and tables will be available at the Annual Mee

significant advantages in terms of restoration of lumbar lordosis, improve-

ment in clinical symptoms, or relief of pain post-operatively.

FDA DEVICE/DRUG STATUS: This abstract does not discuss or include

any applicable devices or drugs.

doi: 10.1016/j.spinee.2011.08.279

219. Recombinant Human Bone Morphogenetic Protein-2

(rhBMP-2) in Posterolateral Spine Fusion: What’s the Correct

Successful Dose/Dosage?

Martin Hoffmann, MD, Clifford B. Jones, MD; Grand Rapids, MI, USA

BACKGROUND CONTEXT: There are continued efforts to enhance the

process of achieving spine fusion and to eliminate the need for autogenous

iliac bone graft harvest. The use of osteobiologics to enhance fusion has

therefore become an important role in these procedures. Despite the fact

of restricted approval, off-label use of BMPs has become a permanent

trend. About 85% of the procedures using BMP were for off-label use.

Especially rhBMP-2 in combination with bone void fillers without or in

combination with iliac crest autograft for posterolateral intertransverse

process fusion has been studied and became more popular over time be-

cause of the need for a higher bonegraft amount for this procedure espe-

cially in patients with poor bone quality. The adjunctive use of rhBMP-2

has been found to result in larger and more consistent fusion masses.

PURPOSE: The purpose of this study was to define the amount of

rhBMP-2 necessary to achieve reliable fusion rates in posterolateral spine

fusion by avoiding greater complication rates.

STUDY DESIGN/SETTING: Retrospective cohort study/ single large or-

thopaedic surgery private practice associated with a tertiary referral spine

center.

PATIENT SAMPLE: 1158 patients.

OUTCOME MEASURES: Union rates related to total rhBMP-2 dose,

union rates related to rhBMP-2 dosage per level. Complications related

to rhBMP were defined as reoperation secondary to failed symptomatic fu-

sion, hyper reaction resulting in compressive fluid collections, hyper for-

mation of bone resulting in neural compression, and infections.

METHODS: During a 7-year period of time (2002–2009), all patients un-

dergoing lumbar posterolateral fusion utilizing of rhBMP-2 (INFUSE)

were retrospectively evaluated within a large orthopaedic surgery private

practice. Patient demographics, comorbidities, number of levels, type of

surgery, and types of bone void filler (BVF) were analyzed. Complications

related to rhBMP were defined as reoperation secondary to failed symp-

tomatic fusion, hyper reaction resulting in compressive fluid collections,

hyper formation of bone resulting in neural compression, and infections.

RESULTS: 1158 consecutive patients were evaluated with 468 (40.4%)

males and 690 (59.6%) females. Average age was 59.2 yo and BMI was

30.7 kg/m2. Number of levels fused was: 1 (414, 35.8%), 2 (469, 40.5%),

3 (162, 14.0%), 4 (70, 6.0%), 5 (19, 1.6%), 6 (11, 0.9%), 7 (7, 0.6%),

8 (4, 0.3%), and 9 (2, 0.2%). Complications including add on stenosis requir-

ing reoperation were 117/1158 (10.1%): Seromawith acute neural compres-

sion 32 (2.8%), excess bone formation with delayed development of neural

compression requiring re-decompression 4 (0.3%), infection requiring de-

bridement 26 (2.2%), and symptomatic nonunion requiring redo fusion

and instrumentation 41 (3.5%). Nonunion was not related to smoking, num-

ber of levels fused, or age. There was an increased risk for nonunion in male

patients (5.1% vs 2.4%, p!.05) and patients with previous BMP exposure

(26%vs2.4%, p!.05). If exposed toBMP, the relative risk of developing a re-

peat symptomatic nonunion is 11%. There was no significantly higher non-

union risk for patients who received only 6 mg rhBMP-2/level. Seroma

formation was significantly higher in patients with higher total BMP (13.4

vs 12.5, t5-1.949, p5.05) and BMP dose/level (7.7 vs 6.7, t51.985, p5.05).

CONCLUSIONS: According to our findings, we recommend a dosage

of 6 mg rhBMP-2 per level for successful instrumented lumbar fusion

and decrease risk of postoperative symptomatic seroma formation. Me-

chanical stability reduces nonunion rate but does not affect the effective

ting and will be included with the post-meeting online content.

114S Proceedings of the NASS 26th Annual Meeting / The Spine Journal 11 (2011) 1S–173S

BMP dose. These findings may lead to a 50 to 75% reduction of bio-

logical implant costs.

FDA DEVICE/DRUG STATUS: rhBMP-2: Investigational/Not approved.

doi: 10.1016/j.spinee.2011.08.280

220. The Effects of Local Insulin Application to Lumbar Spinal

Fusions in a Rat Model

John Koerner, MD1, Praveen Yalamanchili, MD1, Michael Vives, MD2;1Hoboken, NJ, USA; 2UMD - New Jersey Medical School, Department of

Orthopaedics, Newark, NJ, USA

BACKGROUND CONTEXT: Recent studies (Lin, J Orthop Research,

2011) have analyzed the effects of local insulin application to autograft

in a rat segmental defect model. Defects treated with a time released insu-

lin implant had significantly more new bone formation and greater quality

of bone seen on histology, than those treated with sham implants. Applying

time released insulin to the fusion bed of spinal fusions may improve fu-

sion rates.

PURPOSE: To determine if local insulin application with autograft at the

site of posterolateral intertransverse lumbar spinal fusions will increase the

rate of successful fusion in a rat model.

STUDY DESIGN/SETTING: Animal study (Institutional Animal Care

and Use Committee approved): Rat model.

PATIENT SAMPLE: 40 adult Sprague Dawley Rats.

OUTCOME MEASURES: Manual palpation performed by two blinded

fellowship trained Spine surgeonsRadiographs scored by two blinded fel-

lowship trained Spine surgeons using Lenke Criteria: A5solid fusion

mass, B5unilateral fusion mass, C5small fusion mass bilaterally, D5graft

resorptionGrowth factor analysis of transverse process bone by ELISA

(PDGF-AB, TGF-B1, IGF-1, VEGF).

METHODS: 40 Sprague-Dawley rats weighing approximately 500 grams

each underwent posterolateral intertransverse lumbar fusions from L4-L5

utilizing a Wiltse-type approach. After exposure of the transverse processes

and high-speed burr decortication, a Linplant (Linshin Canada) consisting of

95%micro-recrystalized palmitic acid and 5% bovine insulin (experimental

group) or a sham implant consisting of only palmitic acid (control group)was

implanted on the fusion bed with the harvested iliac crest autograft. The

spines of 10 animals from the experimental and 10 from the control group

were harvested at day 4. The remaining 20 were harvested at 8 weeks. The

group harvested at day 4 underwent growth factor analysis by ELISA. The

remaining groups were followed by radiographs at day 28 and at sacrifice

at 8 weeks. In addition to radiographic analysis, the spines harvested at 8

weeks underwent manual palpation testing. Systemic blood glucose levels

were monitored throughout the study.

RESULTS: 39/40 rats had no complications and were sacrificed as

planned. In the groups sacrificed at day 4, there was a significant increase

in IGF-1 in the insulin treatment group vs. controls (0.185 vs. 0.129

(p5.001) Insignificant increases in TGF-B1 from 0.8 to 0.872 (p5.461)

and VEGF 0.552 vs 0.569 (p5.767) and an insignificant decrease in

PDGF-AB from 0.532 to 0.49 (p5.452) were observed. Based on manual

palpation, only 1/9 controls were considered fused, 3/9 were partially

fused, and 5/9 were not fused. The treatment group had 6/10 fusions,

4/10 partial fusions, and 0/10 not fused (p5.0084). Based on radiographs,

1/9 controls had a solid fusion mass, 2/9 had unilateral fusion mass, 3/9

had small fusion mass bilaterally, and 3/9 had no fusion mass. The treat-

ment group had 7/10 solid fusion mass, 3/10 unilateral fusion mass, and

0/10 small fusion mass and 0/10 no fusion mass (p5.0067).

CONCLUSIONS: This study demonstrates the potential role of local in-

sulin as a bone graft enhancer using a rat posterolateral intertransverse

lumbar fusion model. Manual palpation and radiographic outcomes at

8 weeks showed improved fusion rates compared to controls. Growth fac-

tor analysis at day four showed an increased level of IGF-I compared to

controls. Additional analysis including microCT to calculate the amount

of new bone formation, and histology will further define the effects of

insulin in spinal arthrodesis.

All referenced figures and tables will be available at the Annual Mee

FDA DEVICE/DRUG STATUS: Time released insulin implant: Not

approved for this indication.

doi: 10.1016/j.spinee.2011.08.281

221. Subsidence and Osteolysis in Patients Undergoing ALIF with

and without rhBMP-2 Graft Aumentation

Eugene Carragee, MD1, Michael Wildstein2; 1Stanford University School

of Medicine, Redwood City, CA, USA; 2Stanford University, Stanford,

CA, USA

BACKGROUND CONTEXT: Fusion with rhBMP-2 has been associated

with increasing rates of rhBMP-2 associated complications which were not

reported in the original industry-sponsored trials. These complications

have included osteolysis, implant subsidence and migration, inflammatory

cyst formation, radiculitis and retrograde ejaculation. Few controlled trials

unassociated with the device manufacturer have been reported.

PURPOSE: To compare subsidence, implant migration and reoperation

rates after ALIF surgery with supplemental unilateral pedicle screws in

consecutive cohort of subjects with and without rhBMP-2 augmentation

in an anterior interbody femoral ring allograft with buttress screw fixation.

STUDY DESIGN/SETTING: Five year follow-up of consecutive cohort

trial with (n536) and without rhBMP-2 (n548).

PATIENT SAMPLE: Patients having one or two level, anterior and uni-

lateral posterior instrumented fusion for degenerative conditions and isth-

mic spondylolisthesis, followed for 5 years.

OUTCOME MEASURES: VAS, ODI, retrograde ejaculation, radio-

graphic measures of fusion, subsidence, implant migration, screw loosen-

ing and re-operation.

METHODS: Consecutive patients having unilateral transpedicular screw

instrumentation andALIFwith a femoral ring allograph for degenerative con-

ditions or isthmic spondylolisthesis: comparing outcomeswith (after 6/2003)

and without (before 6/2003) rhBMP-2 in (ALIF) were compared using a pro-

tocol follow-up by independent examiner and blinded radiographic review.

RESULTS: Early subsidence, endplate erosion, loss of distraction, loosen-

ing of pedicle screw constructs and reoperation were greater in the

rhBMP-2 group (p!.01). In 25 males there were 3 episodes of retrograde

ejaculation in the rhBMP-2 group, two of which resolved; in 29 males there

were no episodes in the control group. (p5.09) Final pain scores, ODI,

medication intake and occupational duties were all trended worse in the

rhBMP-2 group (p 0.1–0.05). Reoperation rate was higher in the rhBMP-

2 group (p5.05) and occurred predominantly in women. The incidence

of solid fusion was higher in the rhBMP-2 group at one-year (p5.06),

two-years (0.17) but not at five years. Earlier return to work was not differ-

ent in either group, but there was a trend to earlier RTW in the rhBMP-2

group who did heavy labor (p5.21) Satisfaction with surgery was higher

in the control group compared with the rhBMP-2 group (p5.02).

CONCLUSIONS: This is one of the few controlled studies of rhBMP-2

reported by nonindustry-sponsored authors. In our experience the use of

rhBMP-2 in single or double level ALIF with unilateral posterior instru-

mentation has an greater loss of initial alignment, implant subsidence

and reoperations than use of the same construct without rhBMP-2. This ef-

fect was greater in especially in women and may relate to early osteolysis

in less dense bone. The addition of rhBMP-2 had a modest benefit with

earlier radiographic fusion, however this extremely expensive additional

intervention did not improve ultimate clinical outcomes or patient satisfac-

tion. Retrograde ejaculation risk in men may be increased with rhBMP-2

use in a retroperitoneal approach to the lower lumbar spine. The value

added for use of this additional, expensive drug/implant was overall neg-

ative. Value may be improved if use is selectively directed to subjects with

more metabolic morbidity (e.g. predisposing to union) or local pathologic

risk of non-union (e.g. revision or AVN of bone) or longer constructs.

FDA DEVICE/DRUG STATUS: rhBMP-2: Investigational/Not approved;

pedicle screw implant: Approved for this indication.

doi: 10.1016/j.spinee.2011.08.282

ting and will be included with the post-meeting online content.