[Skip to Content]
Sign In
Individual Sign In
Create an Account
Institutional Sign In
OpenAthens Shibboleth
[Skip to Content Landing]
From JAMA
November 16, 2009

Is Use of Bone-Morphogenetic Proteins for Spine Fusion Surgery Cost-effective?

Arch Surg. 2009;144(11):996-997. doi:10.1001/archsurg.2009.185
Abstract

JAMA

Prevalence, Complications, and Hospital Charges Associated With Use of Bone-Morphogenetic Proteins in Spinal Fusion Procedures

Kevin S. Cahill, MD, PhD, MPH; John H. Chi, MD, MPH; Arthur Day, MD; Elizabeth B. Claus, MD, PhD

Context:  No national data exist to examine use of bone-morphogenetic proteins (BMPs) in spinal fusion surgery.

Objective:   To determine the patterns of use and rates of complications and financial charges associated with BMP use in spinal fusion nationally.

Design, Setting, and Patients:   Retrospective cohort study of 328 468 patients undergoing spinal fusion procedures from 2002-2006 identified from the Nationwide Inpatient Sample database, a 20% sample of US community hospitals.

Main Outcome Measures:   The rates of use of BMP among patients undergoing spinal fusion procedures are examined along with complications, length of stay, and hospital charges associated with use of this fusion adjunct.

Results:   The nationwide usage of BMP has increased from 0.69% of all fusions in 2002 to 24.89% of all fusions in 2006. Use of BMP varied by patient sex, race, and primary payer with increased use seen in women (56.26% with BMP vs 53.35% without BMP; odds ratio [OR], 1.12; 95% confidence interval, [CI], 1.09-1.16) and Medicare patients (29.62% with BMP vs 27.16% without BMP; OR, 1.43; 95% CI, 1.31-1.56) and decreased use in nonwhite patients (8.69% with BMP vs 10.23% without BMP; OR, 0.80; 95% CI, 0.75-0.85). When comparing immediate postoperative, in-hospital rates of complications for the year 2006 among patients undergoing spinal fusion by BMP use status, no differences were seen for lumbar, thoracic, or posterior cervical procedures. On univariate analysis and after multivariable adjustment, the use of BMP in anterior cervical fusion procedures was associated with a higher rate of complication occurrence (7.09% with BMP vs 4.68% without BMP; adjusted OR, 1.43; 95% CI, 1.12-1.70) with the primary increases seen in wound-related complications (1.22% with BMP vs 0.65% without BMP; adjusted OR, 1.67; 95% CI, 1.10- 2.53) and dysphagia or hoarseness (4.35% with BMP vs 2.45% without BMP; adjusted OR, 1.63; 95% CI, 1.30-2.05). Bone-morphogenetic protein use was associated with greater inpatient hospital charges across all categories of fusion. Increases between 11% and 41% of total hospital charges were reported, with the greatest percentage increase seen for anterior cervical fusion.

Conclusion:   Bone-morphogenetic protein was used in approximately 25% of all spinal fusions nationally in 2006, with use associated with more frequent complications for anterior cervical fusions and with greater hospital charges for all categories of fusions.

JAMA. 2009;302(1):58-66..

Undergoing a spine arthrodesis can be problematic, even when the most experienced spine surgeons perform them. Twenty years ago, the introduction of segmental spine fixation greatly reduced pseudarthrosis rates. However, despite the wide incorporation of segmental fixation, pseudarthrosis is still reported to be high within the cervical and thoracolumbar spine.1-7 In addition, the procurement of bone graft is associated with high donor site morbidities and chronic pain.8,9

Over the past decade, spine biologics have played an important role in decreasing the risk of pseudarthrosis and eliminating autograft morbidity. In 1965, the family of growth factors known as bone morphogenetic proteins (BMPs) were discovered by Urist.10 Currently, recombinant human BMP-2 (Infuse, Medtronic, Memphis, Tennessee) and BMP-7 (OP-1; Stryker, Kalamazoo, Michigan) have been approved by the Food and Drug Administration (FDA) for use within the spine. In 2002, Infuse was approved for use within adult anterior lumbar interbody fusions and in 2003, OP-1 received a humanitarian use device approval for revision intertransverse lumbar fusions.11,12 Since FDA approval, both Infuse and OP-1 have been used off label in spine fusions.

The study by Cahill et al is a retrospective cohort study of patients from the Nationwide Inpatient Sample database who underwent spinal fusion procedures from 2002 to 2006. The authors report on the rate of BMP use in spine fusions and their association with complications, length of stay, and hospital charges. They report an increase in BMP use from 0.7% in 2002 to 24.3% in 2006. This increase is expected given the FDA approvals in 2002 and 2003 for BMP-2 and BMP-7, respectively. In addition, the authors report that by 2006, at least 20% of BMP use was off label (16% cervical and 4% thoracic). This reported value is likely underestimated given that there is no clear breakdown of the lumbosacral fusions into anterior or posterior groups or whether FDA guidelines where followed.

The authors found that female and white patients were more likely to receive BMP. Although not mentioned, an explanation may be that these patients may have been more likely to be osteoporotic, a known risk factor for pseudarthrosis.13-15 As well, the authors noted that patients with more significant spinal pathology (eg, multilevel fusion, revision surgery, and deformity correction) were likely to receive BMP. In all 3 situations, the risk of pseudarthrosis can be substantially higher and may warrant BMP use.2 Unfortunately, one of the major weaknesses of this study is its lack of patient follow-up. Thus, it is impossible to identify the true cost savings that BMP use could provide over the long-term in patients at higher risk of pseudarthrosis.

Regarding complications associated with BMP use, Medtronic released a safety alert with regards to the off- label use of recombinant human BMP-2 in anterior cervical spine fusions in 2004.16 Postoperative complications have been reported to occur in as much as 28% of patients,17,18 and this current study reports a complication rate of 7.1%. Complications such as edema, dysphagia, respiratory distress, hematomas, and reoperation appear to be dose dependent.19 Therefore, a lower dose may obviate a greater risk of complication and still maintain the clinical benefits. Regardless, BMP use in the anterior cervical spine must be done with caution and possibly be avoided until a more appropriate dose can be studied.

Notably, use of the Nationwide Inpatient Sample Database has allowed these authors to accrue data from many patients (328 468), thus potentially making any findings more significant. However, such administrative databases have been shown to be inaccurate with respect to multiple patient characteristics, most notably diagnosis and treatment received, thus making any conclusions potentially invalid.20 Furthermore, using this database, the authors could not qualify or quantify the actual inpatient costs associated with the direct use of BMP. Although there is no doubt that BMP use adds to hospital costs, it is not clear from this study whether sicker patients were more costly regardless of BMP use. In this way, without patient follow-up and without delineating the actual costs associated with inpatient hospital care, the study fails to provide insight on the most important question regarding use of BMP: Is use of BMP in the spine cost-effective? Nonetheless, the authors should be commended on presenting the trends of BMP use in the United States over the last several years and highlighting procedures associated with potentially increased risk (eg, anterior cervical fusion). More rigorous cost analysis studies coupled with patient outcomes may eventually allow for more specific recommendations for BMP use, which may improve both treatment efficacy and cost efficiency for the patient.

Correspondence: Dr Sciubba, Johns Hopkins Medical Institutions, 600 N Wolfe St, Meyer 7-109, Baltimore, MD 21287 (dsciubb1@jhmi.edu).

Author Contributions:Study concept and design: Cardoso and Sciubba. Analysis and interpretation of data: Cardoso and Sciubba. Drafting of the manuscript: Cardoso and Sciubba. Critical revision of the manuscript for important intellectual content: Cardoso and Sciubba. Statistical analysis: Sciubba. Study supervision: Sciubba.

Financial Disclosure: The Spinal Oncology Study Group, of which Dr Sciubba is a member, is supported by Medtronic. Dr Sciubba has received honorarium for a talk from DePuy Spine.

References
1.
Bridwell  KHSedgewick  TAO'Brien  MFLenke  LGBaldus  C The role of fusion and instrumentation in the treatment of degenerative spondylolisthesis with spinal stenosis.  J Spinal Disord 1993;6 (6) 461- 472PubMedGoogle ScholarCrossref
2.
Kim  YJBridwell  KHLenke  LGRhim  SCheh  G Pseudarthrosis in long adult spinal deformity instrumentation and fusion to the sacrum: prevalence and risk factor analysis of 144 cases.  Spine (Phila Pa 1976) 2006;31 (20) 2329- 2336PubMedGoogle ScholarCrossref
3.
McGuire  RAAmundson  GM The use of primary internal fixation in spondylolisthesis.  Spine (Phila Pa 1976) 1993;18 (12) 1662- 1672PubMedGoogle ScholarCrossref
4.
Wang  JC McDonough  PWEndow  KKanim  LEDelamarter  RB The effect of cervical plating on single-level anterior cervical discectomy and fusion.  J Spinal Disord 1999;12 (6) 467- 471PubMedGoogle ScholarCrossref
5.
Wang  JC McDonough  PWEndow  KKDelamarter  RB Increased fusion rates with cervical plating for two-level anterior cervical discectomy and fusion.  Spine (Phila Pa 1976) 2000;25 (1) 41- 45PubMedGoogle ScholarCrossref
6.
Wang  JC McDonough  PWKanim  LEEndow  KKDelamarter  RB Increased fusion rates with cervical plating for three-level anterior cervical discectomy and fusion.  Spine (Phila Pa 1976) 2001;26 (6) 643- 647PubMedGoogle ScholarCrossref
7.
West  JL  IIIBradford  DSOgilvie  JW Results of spinal arthrodesis with pedicle screw-plate fixation.  J Bone Joint Surg Am 1991;73 (8) 1179- 1184PubMedGoogle Scholar
8.
Banwart  JCAsher  MAHassanein  RS Iliac crest bone graft harvest donor site morbidity: a statistical evaluation.  Spine (Phila Pa 1976) 1995;20 (9) 1055- 1060PubMedGoogle ScholarCrossref
9.
Silber  JSAnderson  DGDaffner  SD  et al.  Donor site morbidity after anterior iliac crest bone harvest for single-level anterior cervical discectomy and fusion.  Spine (Phila Pa 1976) 2003;28 (2) 134- 139PubMedGoogle ScholarCrossref
10.
Urist  MR Bone: formation by autoinduction.  Science 1965;150 (698) 893- 899PubMedGoogle ScholarCrossref
11.
Burkus  JKTransfeldt  EEKitchel  SHWatkins  RGBalderston  RA Clinical and radiographic outcomes of anterior lumbar interbody fusion using recombinant human bone morphogenetic protein-2.  Spine (Phila Pa 1976) 2002;27 (21) 2396- 2408PubMedGoogle ScholarCrossref
12.
Vaccaro  ARPatel  TFischgrund  J  et al.  A pilot safety and efficacy study of OP-1 putty (rhBMP-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions.  Eur Spine J 2003;12 (5) 495- 500PubMedGoogle ScholarCrossref
13.
Cummings  SRKelsey  JLNevitt  MCO’Dowd  KJ Epidemiology of osteoporosis and osteoporotic fractures.  Epidemiol Rev 1985;7178- 208PubMedGoogle Scholar
14.
Melton  LJ  IIIKan  SHFrye  MAWahner  HWO’Fallon  WMRiggs  BL Epidemiology of vertebral fractures in women.  Am J Epidemiol 1989;129 (5) 1000- 1011PubMedGoogle Scholar
15.
Stephen  ABWallace  WA The management of osteoporosis.  J Bone Joint Surg Br 2001;83 (3) 316- 323PubMedGoogle ScholarCrossref
16.
Safety Alert  RWT INFUSE Bone Graft.  Memphis, TN Medtronic Sofamor Danek2004;
17.
Shields  LBRaque  GHGlassman  SD  et al.  Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior cervical spine fusion.  Spine (Phila Pa 1976) 2006;31 (5) 542- 547PubMedGoogle ScholarCrossref
18.
Smucker  JDRhee  JMSingh  KYoon  STHeller  JG Increased swelling complications associated with off-label usage of rhBMP-2 in the anterior cervical spine.  Spine (Phila Pa 1976) 2006;31 (24) 2813- 2819PubMedGoogle ScholarCrossref
19.
Baskin  DSRyan  PSonntag  VWestmark  RWidmayer  MA A prospective, randomized, controlled cervical fusion study using recombinant human bone morphogenetic protein-2 with the CORNERSTONE-SR allograft ring and the ATLANTIS anterior cervical plate.  Spine (Phila Pa 1976) 2003;28 (12) 1219- 1225PubMedGoogle Scholar
20.
Woodworth  GFBaird  CJGarces-Ambrossi  GTonascia  JTamargo  RJ Inaccuracy of the administrative database: comparative analysis of two databases for the diagnosis and treatment of intracranial aneurysms.  Neurosurgery 2009;65 (2) 251- 257PubMedGoogle ScholarCrossref
×