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Vertebroplasty - 2009 NEJM
Studies Critical Review Distinguished Engineering Fellow
DePuy Spine, a Johnson & Johnson Co.
Prestige Adjunct Professor
Bioengineering Dept. University of
Toledo
Co-Founder & Treasurer of the
S.P.I.N.E Society
www.neareastspine.org
Contact: [email protected]
Hassan Serhan, PhD
http://www.neareastspine.org/http://www.neareastspine.org/8/7/2019 Serhan_Vertebroplasty
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Vertebroplasty2009 NEJM Studies
Critical Review
Hassan Serhan, Ph.D.Distinguished Fellow
Employee of DePuy Spine
a J&J company
Prestige Adjunct ProfessorThe Bioengineering Dept.University of Toledo, OH
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OsteoporosisA Public Health Problem
100 Million People Worldwide at Risk
28 Million People U.S. at Risk
1.5 Million Fragility Fractures in U.S. 700,000 spine
300,000 hip
250,000 wrist
250,000 other
National Osteoporosis Foundation
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Aug 31, 2000 Sept 3, 2000
16kyphosis
25kyphosis
Deformity Progression
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CG
Deformity Progression
Center of gravity (CG) movesforward
Axial Loads + Large bendingmoment created
Posterior muscles andligaments must counterbalanceincreased bending
Osteoporotic anterior spine
must resist larger compressivestresses
White and Panjabi 1990
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Cements Augmentation of VCF Indication (product label-FDA)
Bone cements used in vertebroplasty are indicated for fixation of
pathological fractures of the vertebral body using vertebroplasty orkyphoplasty procedures.
Medicare indications:
Painful osteolytic vertebral body metastatic disease;
Painful multiple myeloma involving the vertebral body;
Painful and/or aggressive hemangioma;
Painful, debilitating, osteoporotic vertebral collapse/ compressionfractures that have not responded to conservative medicaltreatment.
Severe pain and functional debilitation related to activities of daily
living due to chronic vertebral collapse/compression fractures thatrequire hospitalization for pain control and treatment.
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1. Disc-O-Tech Medical Technologies Ltd. Confidence EX High Viscosity Bone Cement Special10(k); K062424. August 2006. Accessed November 18,2009 at http://www.accessdata.fda.gov/cdrh_docs/pdf6/K062424.pdf .
2. Nationwide Inpatient Sample, 2007; Patients with ICD-9-CM 81.65 as primary diagnosis.3. Premier Hospital and Drug Database, 2007-2008. Patients with osteoporotic compression fracture (65% inpatient; 35% outpatient). Data on file. DePuy
Spine.4. Taylor RS, Taylor RJ, Fritzell P. Balloon kyphoplasty for vertebroplasty for vertebral compression fractures: a comparative systematic review of efficacy
and safety. Spine 2006;31:274755.5. Nationwide Inpatient Sample, 2006; Patients with ICD-9-CM 733.13 (pathologic vertebral body fracture) as primary diagnosis.
http://www.accessdata.fda.gov/cdrh_docs/pdf6/K062424.pdfhttp://www.accessdata.fda.gov/cdrh_docs/pdf6/K062424.pdf8/7/2019 Serhan_Vertebroplasty
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These procedures are offered only when traditionalmedical therapy has not provided pain relief or pain issubstantially altering the patients lifestyle.it is theposition of the Societies that vertebral
augmentation with vertebroplasty or kyphoplastyis a medically appropriate therapy for thetreatment of painful vertebral compressionfracturesrefractory to medical therapy when
performed for the medical indications outlined in thepublished standards
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M.E. Jensen, J.K. McGraw, J.F. Cardella, and J.A. Hirsch. Position Statement on Percutaneous Vertebral Augmentation: A Consensus StatementDeveloped by the American Society of Interventional and Therapeutic Neuroradiology, Society of Interventional Radiology, American Association ofNeurological Surgeons/Congress of Neurological Surgeons, and American Society of Spine Radiology
AJNR Am. J. Neuroradiol., September 1, 2007; 28(8): 1439 - 1443.
2007 - Consensus statement
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Literature Reviews -Vertebroplasty Studies
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Study StudiesReviewed
# Patients Pre-op VAS:mean (range)
Post-op VAS:mean (range)
Eck et al(2008)
103 7,587 8.36 2.68
Hochmuth et
al. (2006)
30 2,0868.1
(6.49.7)
2.6
(1.73.9)
Hulme et al.(2006)
47 2,9588.2
(7.88.6)3.0
(2.43.6)
1 . McGirt, MJ, Parker, SL, Wolinsky, JP, Witham, TF, Bydon, A, and Gokaslan, ZL. Vertebroplasty and kyphoplasty for the treatment of
vertebral compression fractures: an evidenced-based review of the literature. Spine J. 2009;9(6):501-508.
Significant within-group reductions in VASfrom greater than 8/10 base-line pain1
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Kyphoplasty versus Conservative Care(FREE trial)1
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StudyComparator/Study
DesignPatients
Results at One Year(Between-group difference)
Wardlaw et al.(2009) (FREEtrial)
PercutaneousKyphoplasty (PK)(n = 149)
Conservative Care(n = 151)
Randomized, controlled,multi-center (21 sites, 8countries)
Fracture edema onMRI
Fractures estimatedto be less than 3months of age
Mean fracture age of5.6 weeks
SF-36 PCS score: 35 point (1654;p=00004) improvement in the kyphoplastycohort (p = 0.0004) relative to controls
Back pain: 09 point (0315; p=00034)improvement in the kyphoplasty improvementrelative to controls
Statistically significant improvement in pain and
quality of life at 12 months
1. Wardlaw D, Cummings S, Van Meirhaeghe J, et al. An international multicentered randomized comparison of balloon kyphoplasty
and nonsurgical management in patients with acute vertebral body compression fractures. Lancet 2009; 373: 101624.
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NEJM Blinded RCTs: PV Vs Control
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1. Kallmes, DF, Comstock, BA, Heagerty, PJ, Turner, JA, Wilson, DJ, Diamond, TH, Edwards, R, Gray, LA, Stout, L, Owen, S,
Hollingworth, W, Ghdoke, B, nnesley-Williams, DJ, Ralston, SH, and Jarvik, JG. A randomized trial of vertebroplasty for osteoporotic
spinal fractures. N Engl J Med. 2009;361(6):569-579.
StudyComparator/Sample size/
DesignInclusion Criteria Primary Outcome
Pain Duration(weeks)
Baseline VAS,Mean (SD)
NEJM
Kallmes etal., INVEST
trial (2009)1
Percutaneous
vertebroplasty
(n = 68)
Control
(n = 63)
RCT: 11 sites
Minimum pain at entry of 3.0/101 to 3 painful osteoporotic
vertebral compression fractures
Fracture less than one-year oldFracture confirmed by x-ray
MRI or bone scan only used in
cases with uncertain fracture age
Primary outcome at one
month: change on Roland-
Morris Disability Questionnaire
(RDQ)Criteria for success of 3.0
point between-group
difference
PV: 16
Control: 20
PV: 6.9 (2.0)
Control: 7.2 (1.8)
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NEJM Blinded RCTs: PV Versus Control(Contd.)
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NEJM - Kallmes et al. (2009) (INVEST trial) 1
PV Placebo P-valueN 68 63 NA
Pain intensity (1 mo) 3.9 4.6 0.19
RDQ (1 mo) 12.0 13.0 0.49
Crossover 1 3 mos 8 (12%) 27 (43%) < 0.0001
Clinically meaningful reduction in pain* 64% 48% 0.06
Authors conclusions
Improvements in pain and pain-related disabilityassociated with osteoporotic compression fractures inpatients treated with vertebroplasty were similar to theimprovements in a control group
*% with 30% decrease from baseline VAS
RDQ = Roland Morris Disability questionnaire
NR = Not reported
1. Kallmes, DF, Comstock, BA, Heagerty, PJ, Turner, JA, Wilson, DJ, Diamond, TH, Edwards, R, Gray, LA, Stout, L, Owen, S,
Hollingworth, W, Ghdoke, B, nnesley-Williams, DJ, Ralston, SH, and Jarvik, JG. A randomized trial of vertebroplasty for osteoporoticspinal fractures. N Engl J Med. 2009;361(6):569-579.
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North American Spine Society (NASS)Study Limitations1
Fracture Acuity Imaging (MRI or bone scan) not required to verify fracture age
Fracture age
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NASSStudy Limitations1 (cont)
Control Group
Kallmes et al.
An alternative intervention rather than a sham
Anesthetic injection into facet capsule or periosteum (Kallmes etal.) may have resulted in pain relief (though not fracture pain
relief)
Outcomes
Kallmes et al.
Did not seek to verify source of back pain (e.g., nopalpation/percussion to verify source of pain)
Crossover at one month suggests superiority of vertebroplasty:43% control versus 12% for vertebroplasty (p < 0.0001)
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1. North American Spine Society: Newly Released Vertebroplasty RCTs: A Tale of Two Trials. Accessed November 16, 2009 at
http://www.spine.org/Documents/NASSComment_on_Vertebroplasty.pdf.
http://www.spine.org/Documents/NASSComment_on_Vertebroplasty.pdfhttp://www.spine.org/Documents/NASSComment_on_Vertebroplasty.pdfhttp://www.spine.org/Documents/NASSComment_on_Vertebroplasty.pdf8/7/2019 Serhan_Vertebroplasty
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NASSs Recommendations1
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future PRCTs might benefit from a more strict mechanism bywhich patients withtruly acute pain relatable to an osteoporoticVCF are enrolled
it is time for cooler heads to prevailthe conclusions drawn by
the authors, however, may not be as decisive as they appear.More practical conclusions should be made based on athorough and systematic review of all the literature in order tobetter define the subgroup of patients for whichvertebroplasty might be most appropriate.
1. North American Spine Society: Newly Released Vertebroplasty RCTs: A Tale of Two Trials. Accessed November 16, 2009 at
http://www.spine.org/Documents/NASSComment_on_Vertebroplasty.pdf.
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Additional Study Limitations
Mid-trial adjustments
Inclusion criteria
Relaxation of inclusion criteria to include patients with 3.0/10 VASscores
Statistical power and sample size
Enrollment targets were adjusted at mid-trial
Kallmes et al
Reduced from 250 (pre-specified) to 130 patients
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Additional Study Limitations (cont)
Mid-trial adjustmentsOutcomes
Success criteria were adjusted at mid-trial
Kallmes et al. - Roland Morris Disability Questionnaire(RDQ) adjusted from 2.5 (pre-specified) to 3.0
VAS improvement adjusted from 1.0 to 1.5
There was a trend toward a higher rate of clinically meaningfulimprovement in pain in the vertebroplasty group, than in thecontrol group(64% vs. 48% P=0.06)
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Conclusions
Data from thousands of patients demonstrate pain reduction withvertebroplasty.
The multicenter, randomized controlled trial of kyphoplasty versusconservative care reveals statistically significant and clinically meaningfulimprovement in pain and quality of life.
The recent NEJM articles have multiple limitations that preclude definitiveconclusion about the value of vertebroplasty, including
Selection bias; Inadequate sample size and statistical power;
No confirmation of fracture age;
Mid-trial adjustment to sample size targets and improvementthresholds; and
Flaws in the measurement of pain; and Use of an active control that is not standard of care for patients with
VCF.
Ongoing and planned studies will enhance the evidence base fortreatment of VCFs
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