0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Research Letters |

Off-Label Use of Bone Morphogenetic Proteins in Pediatric Spinal Arthrodesis FREE

Emily Dodwell, MD, MPH; Brian Snyder, MD, PhD; James Wright, MD, MPH
[+] Author Affiliations

Author Affiliations: Hospital for Special Surgery, New York, New York (Dr Dodwell; dodwelle@hss.edu); Hospital for Sick Children, Toronto, Ontario, Canada (Dr Snyder); and Children's Hospital Boston, Boston, Massachusetts (Dr Wright).


Letters Section Editor: Jody W. Zylke, MD, Senior Editor.

More Author Information
JAMA. 2012;308(14):1429-1432. doi:10.1001/jama.2012.12929.
Text Size: A A A
Published online

To the Editor: Arthrodesis of the spine is frequently performed in children. Although nonunion occurs frequently in adults, children rarely experience nonunion.1 We are aware of no evidence to support the need for augmentation beyond instrumentation and autograft bone grafting in pediatric spinal arthrodesis.

Bone morphogenetic proteins (BMPs) are approved for limited use in adults when healing may be suboptimal.2,3 In addition to concerns about possible carcinogenesis, complications include wound dehiscence, spinal stenosis, and respiratory complications.4 The US Food and Drug Administration has not approved the use of BMPs in children.

We determined the prevalence of BMP use, associated complications, costs, and potential predictors of use in pediatric spinal arthrodesis in the United States.

The Kidś Inpatient Database, Healthcare Cost and Utilization Project, a sample of 4121 US hospitals containing 10% of uncomplicated births and 80% of complicated pediatric admissions representing approximately 30% of total pediatric admissions, is weighted to allow calculation of national estimates.5 We included children aged 18 years or younger who had undergone primary or revision spine arthrodesis in 2009 using International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses and procedure codes as previously described by Cahill et al.6

SAS version 9.2 (SAS Institute Inc) was used, accounting for the complex survey design to calculate appropriate standard errors and P values and to provide nationally representative weighted estimates of prevalence of BMP use, in-hospital complications, length of stay, and in-hospital costs. Costs were estimated from supplied charges data using hospital-specific cost-to-charge ratios from the Healthcare Cost and Utilization Project.

Multivariable logistic regression was used to determine the independent association of diagnoses, comorbidities, demographic factors, and insurance status with BMP use (Table). Complications assessed included medical, neurological, wound healing, infectious, and those related to breathing and dysphagia.6 The institutional review board at the Hospital for Sick Children approved the study and waived participant consent.

Table Graphic Jump LocationTable. Adjusted Factors Associated With Use of Bone Morphogenetic Proteins (BMPs)

In 2009, 8289 pediatric spinal arthrodeses were in the Kidś Inpatient Database. Nationally, BMP was estimated to be used in 9.2% (95% CI, 7.3%-11.0%; unweighted n = 771) of cases. The estimated prevalence of in-hospital complications in those who received BMP was 3.0% (95% CI, 2.0%-4.1%; unweighted n = 24) and in those who did not receive BMP was 3.6% (95% CI, 3.0%-4.2%; unweighted n = 271) (Rao-Scott χ2 = 0.74; P = .39 for comparison across BMP groups).

The median total in-hospital adjusted costs for patients receiving BMP was $47 136 (interquartile range [IQR], $30 692-$73 848) and in those not receiving BMP was $43 126 (IQR, $31 246-$59 849) (P < .001). Adjusted analysis of log-transformed costs showed that surgeries using BMP were 19% (95% CI, 10%-28%) more costly than those not using BMP. Median length of stay for patients receiving BMP was 4.6 days (IQR, 3.2-6.9 days) and for those not receiving BMP was 4.6 days (IQR, 3.5-6.1 days) (P = .70).

Use of BMP was associated with older age, lumbosacral arthrodeses, fewer vertebrae fused, spondylolisthesis, neurofibromatosis, revision fusions, and surgeries performed in the Midwest. Use of BMP was less frequent in idiopathic scoliosis, specialized pediatric hospitals, and in patients with Medicare or Medicaid health coverage (Table).

Given the lack of indication for augmentation of pediatric spinal arthrodesis, the use of BMP in 9.2% of patients is surprising. Although no difference in the rate of in-hospital complications was demonstrated, most complications previously reported with BMP are late complications and would not be expected to occur during hospitalization. While it is possible that some unmeasured factors account for the increase in costs associated with BMP use, our adjusted analysis showed that surgeries using BMP were 19% more costly than those that did not involve BMP use. Although BMP was used for diagnoses considered higher risk for nonunion, such as neurofibromatosis, BMP was still used frequently in idiopathic scoliosis and for other low-risk diagnoses.

This study was limited by lack of longitudinal data in the Kidś Inpatient Database, as well as lack of details on dosage and type of BMP. Use of BMP should not be routine in pediatric spine arthrodesis until it has been shown to be safe and beneficial.

Author Contributions: Dr Dodwell had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Dodwell, Snyder, Wright.

Acquisition of data: Dodwell.

Analysis and interpretation of data: Dodwell, Snyder, Wright.

Drafting of the manuscript: Dodwell, Wright.

Critical revision of the manuscript for important intellectual content: Dodwell, Snyder, Wright.

Statistical analysis: Dodwell.

Study supervision: Snyder, Wright.

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Dodwell reported receiving a grant from the Ruth Jackson Orthopedic Society/Orthopedic Education and Research Fund. Dr Wright reported receiving reimbursement for travel expenses incurred as a visiting professor. Dr Snyder did not report any disclosures.

Funding/Support: The source of the data, the Kids' Inpatient Database, is part of the Healthcare Cost and Utilization Project sponsored by the Agency for Healthcare Research and Quality.

Role of the Sponsor: The Agency for Healthcare Research and Quality had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.

Additional Contributions: We acknowledge Charles Victor, MSc, PStat (Institute for Clinical Evaluative Sciences and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada), for his assistance with the statistical analysis. Mr Victor received compensation for his work on this project.

Dewald R, edSpinal Deformities: The Comprehensive Text. New York, NY: Thieme Medical Publishers; 2003:644
US Food and Drug Administration.  OP-1 - H010002. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm085026.htm. Accessibility verified September 11, 2012
US Food and Drug Administration.  F. InFUSE Bone Graft/LT-CAGE™ Lumbar Tapered Fusion Device—P000058. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm083423.htm. Accessibility verified September 11, 2012
Mroz TE, Wang JC, Hashimoto R, Norvell DC. Complications related to osteobiologics use in spine surgery: a systematic review.  Spine (Phila Pa 1976). 2010;35(9):(suppl)  S86-S104
PubMed   |  Link to Article
Agency for Healthcare Research and Quality.  Healthcare Cost and Utilization Project (HCUP): HCUP Kids' Inpatient Database, 2006 and 2009. http://www.hcup-us.ahrq.gov/kidoverview.jsp. Accessibility verified September 11, 2012
Cahill ME, Xie Z, Day M,  et al.  Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes [published correction appears in Proc Natl Acad Sci U S A. 2009;106(39):16890].  Proc Natl Acad Sci U S A. 2009;106(31):13058-13063
PubMed   |  Link to Article

Figures

Tables

Table Graphic Jump LocationTable. Adjusted Factors Associated With Use of Bone Morphogenetic Proteins (BMPs)

References

Dewald R, edSpinal Deformities: The Comprehensive Text. New York, NY: Thieme Medical Publishers; 2003:644
US Food and Drug Administration.  OP-1 - H010002. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm085026.htm. Accessibility verified September 11, 2012
US Food and Drug Administration.  F. InFUSE Bone Graft/LT-CAGE™ Lumbar Tapered Fusion Device—P000058. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm083423.htm. Accessibility verified September 11, 2012
Mroz TE, Wang JC, Hashimoto R, Norvell DC. Complications related to osteobiologics use in spine surgery: a systematic review.  Spine (Phila Pa 1976). 2010;35(9):(suppl)  S86-S104
PubMed   |  Link to Article
Agency for Healthcare Research and Quality.  Healthcare Cost and Utilization Project (HCUP): HCUP Kids' Inpatient Database, 2006 and 2009. http://www.hcup-us.ahrq.gov/kidoverview.jsp. Accessibility verified September 11, 2012
Cahill ME, Xie Z, Day M,  et al.  Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes [published correction appears in Proc Natl Acad Sci U S A. 2009;106(39):16890].  Proc Natl Acad Sci U S A. 2009;106(31):13058-13063
PubMed   |  Link to Article

Letters

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 2

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections