Use of bone morphogenetic protein among patients undergoing fusion for degenerative diagnoses in the United States, 2002 to 2012

doi:10.1016/j.spinee.2014.12.010

. 2015 Apr 1;15(4):692-9.

doi: 10.1016/j.spinee.2014.12.010. Epub 2014 Dec 15.

Use of bone morphogenetic protein among patients undergoing fusion for degenerative diagnoses in the United States, 2002 to 2012

Brook I Martin¹, Jon D Lurie², Anna N A Tosteson³, Richard A Deyo⁴, Farrokh R Farrokhi⁵, Sohail K Mirza⁶

Affiliations

¹ The Dartmouth Institute for Health Policy and Clinical Practice, 35 Centerra Parkway, Lebanon, NH 03766, USA; Department of Orthopaedic Surgery Dartmouth-Hitchcock Medical Center, One Medical Center Dr., Lebanon, NH 03756, USA. Electronic address: Brook.I.Martin@Dartmouth.edu.
² The Dartmouth Institute for Health Policy and Clinical Practice, 35 Centerra Parkway, Lebanon, NH 03766, USA; Department of Orthopaedic Surgery Dartmouth-Hitchcock Medical Center, One Medical Center Dr., Lebanon, NH 03756, USA; Department of Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Dr., Lebanon, NH 03756, USA.
³ The Dartmouth Institute for Health Policy and Clinical Practice, 35 Centerra Parkway, Lebanon, NH 03766, USA; Department of Community and Family Medicine. Dartmouth-Hitchcock Medical Center, One Medical Center Dr, Lebanon, NH 03756, USA.
⁴ Department of Family Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA; Department of Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA; Department of Public Health & Preventive Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA.
⁵ Department of Neurosurgery, Virginia Mason Medical Center, 1100 9th Ave., Mail Stop X7-NS, Seattle, WA 98111, USA.
⁶ Department of Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Dr., Lebanon, NH 03756, USA.

PMID: 25523380
PMCID: PMC4375057
DOI: 10.1016/j.spinee.2014.12.010

Use of bone morphogenetic protein among patients undergoing fusion for degenerative diagnoses in the United States, 2002 to 2012

Brook I Martin et al. Spine J. 2015.

. 2015 Apr 1;15(4):692-9.

doi: 10.1016/j.spinee.2014.12.010. Epub 2014 Dec 15.

Authors

Brook I Martin¹, Jon D Lurie², Anna N A Tosteson³, Richard A Deyo⁴, Farrokh R Farrokhi⁵, Sohail K Mirza⁶

Affiliations

¹ The Dartmouth Institute for Health Policy and Clinical Practice, 35 Centerra Parkway, Lebanon, NH 03766, USA; Department of Orthopaedic Surgery Dartmouth-Hitchcock Medical Center, One Medical Center Dr., Lebanon, NH 03756, USA. Electronic address: Brook.I.Martin@Dartmouth.edu.
² The Dartmouth Institute for Health Policy and Clinical Practice, 35 Centerra Parkway, Lebanon, NH 03766, USA; Department of Orthopaedic Surgery Dartmouth-Hitchcock Medical Center, One Medical Center Dr., Lebanon, NH 03756, USA; Department of Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Dr., Lebanon, NH 03756, USA.
³ The Dartmouth Institute for Health Policy and Clinical Practice, 35 Centerra Parkway, Lebanon, NH 03766, USA; Department of Community and Family Medicine. Dartmouth-Hitchcock Medical Center, One Medical Center Dr, Lebanon, NH 03756, USA.
⁴ Department of Family Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA; Department of Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA; Department of Public Health & Preventive Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA.
⁵ Department of Neurosurgery, Virginia Mason Medical Center, 1100 9th Ave., Mail Stop X7-NS, Seattle, WA 98111, USA.
⁶ Department of Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Dr., Lebanon, NH 03756, USA.

PMID: 25523380
PMCID: PMC4375057
DOI: 10.1016/j.spinee.2014.12.010

Abstract

Background context: Use of bone morphogenetic protein (BMP) as an adjunct to spinal fusion surgery proliferated after Food and Drug Administration (FDA) approval in 2002. Major safety concerns emerged in 2008.

Purpose: The purpose of this study was to examine whether published concerns about the safety of BMP altered clinical practice.

Study design/setting: The study design involved the analysis of the National Inpatient Sample from 2002 through 2012.

Patient sample: Adults (older than 20 years) undergoing an elective fusion operation for common degenerative diagnoses were identified using codes from the International Classification of Diseases, ninth revision, Clinical Modification.

Outcome measures: Outcome measures were proportion of cervical and lumbar fusion operations, over time, that involved BMP.

Methods: We aggregated the data into a monthly time series and reported the proportion of cervical and lumbar fusion operations, over time, that involved BMP. Autoregressive Integrated Moving Average, a regression model for time series data, was used to test whether there was a statistically significant change in the overall rate of BMP use after an FDA Public Health Notification in 2008.

Results: Use of BMP in spinal fusion procedures increased rapidly until 2008, involving up to 45.2% of lumbar and 13.5% of cervical fusions. Bone morphogenetic protein use significantly decreased after the 2008 FDA Public Health Notification and revelations of financial payments to surgeons involved in the pivotal FDA-approved trials. For lumbar fusion, the average annual increase was 7.9 percentage points per year from 2002 to 2008, followed by an average annual decrease of 11.7 percentage points thereafter (p≤.001). Use of BMP in cervical fusion increased 2.0% per year until the FDA Public Health Notification, followed by a 2.8% per year decrease (p=.035).

Conclusions: Use of BMP in spinal fusion surgery declined subsequent to published safety concerns and revelations of financial conflicts of interest for investigators involved in the pivotal clinical trials.

Keywords: Bone morphogenetic proteins; Epidemiology; Nationwide inpatient sample; Spinal fusion; Surgical safety; rhBMP-2.

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References

1. Food and Drug Administration. Summary of Safety and Effectiveness Data (InFUSE Bone Graft/LT-Cage Lumbar Tapered Fusion Device) 2002
1. Lad SP, Nathan JK, Boakye M. Trends in the use of bone morphogenetic protein as a substitute to autologous iliac crest bone grafting for spinal fusion procedures in the United States. Spine. 2011;36(4):E274–E281. (Phila Pa 1976) - PubMed
1. Ong KL, Villarraga ML, Lau E, Carreon LY, Kurtz SM, Glassman SD. Off-label use of bone morphogenetic proteins in the United States using administrative data. Spine. 2010;35(19):1794–1800. (Phila Pa 1976) - PubMed
1. Food and Drug Administration. FDA Public Health Notification: Life-threatening complications associated with recombinant human bone morphogenetic protein in cervical spine fusion. Report issued July 1, 2008.
1. Cahill KS, Chi JH, Day A. Prevalence, complications, and hospital charges associated with use of bone-morphogenetic proteins in spinal fusion procedures. JAMA. 2009;302(1):58–66. - PubMed

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[1] Food and Drug Administration. Summary of Safety and Effectiveness Data (InFUSE Bone Graft/LT-Cage Lumbar Tapered Fusion Device) 2002

[2] Food and Drug Administration. Summary of Safety and Effectiveness Data (InFUSE Bone Graft/LT-Cage Lumbar Tapered Fusion Device) 2002

[3] Lad SP, Nathan JK, Boakye M. Trends in the use of bone morphogenetic protein as a substitute to autologous iliac crest bone grafting for spinal fusion procedures in the United States. Spine. 2011;36(4):E274–E281. (Phila Pa 1976) - PubMed

[4] Lad SP, Nathan JK, Boakye M. Trends in the use of bone morphogenetic protein as a substitute to autologous iliac crest bone grafting for spinal fusion procedures in the United States. Spine. 2011;36(4):E274–E281. (Phila Pa 1976) - PubMed

[5] Ong KL, Villarraga ML, Lau E, Carreon LY, Kurtz SM, Glassman SD. Off-label use of bone morphogenetic proteins in the United States using administrative data. Spine. 2010;35(19):1794–1800. (Phila Pa 1976) - PubMed

[6] Ong KL, Villarraga ML, Lau E, Carreon LY, Kurtz SM, Glassman SD. Off-label use of bone morphogenetic proteins in the United States using administrative data. Spine. 2010;35(19):1794–1800. (Phila Pa 1976) - PubMed

[7] Food and Drug Administration. FDA Public Health Notification: Life-threatening complications associated with recombinant human bone morphogenetic protein in cervical spine fusion. Report issued July 1, 2008.

[8] Food and Drug Administration. FDA Public Health Notification: Life-threatening complications associated with recombinant human bone morphogenetic protein in cervical spine fusion. Report issued July 1, 2008.

[9] Cahill KS, Chi JH, Day A. Prevalence, complications, and hospital charges associated with use of bone-morphogenetic proteins in spinal fusion procedures. JAMA. 2009;302(1):58–66. - PubMed

[10] Cahill KS, Chi JH, Day A. Prevalence, complications, and hospital charges associated with use of bone-morphogenetic proteins in spinal fusion procedures. JAMA. 2009;302(1):58–66. - PubMed

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Use of bone morphogenetic protein among patients undergoing fusion for degenerative diagnoses in the United States, 2002 to 2012

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Use of bone morphogenetic protein among patients undergoing fusion for degenerative diagnoses in the United States, 2002 to 2012

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