Serhan_Vertebroplasty

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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/


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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.pdf


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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.pdf


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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.
http://www.spine.org/Documents/NASSComment_on_Vertebroplasty.pdfhttp://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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