Key Clinical Articles

Article

Description

RCT

Wardlaw Lancet 2009 (16003424)

BKP vs. NSM, 1 year f/u

2-year
Outcomes

Garfin Spine 2006 (16000695)

BKP reduces pain, improves ADLs, QOL

Ledlie Spine 2006 (16000567)

BKP reduces pain, increases VB height

Concurrently
Controlled

Komp J Miner Stoffwechs 2004 (16000347)

BKP vs. NSM, acute fractures, 6 mo f/u

Grafe Osteo Int 2005 (16000583)

BKP vs. NSM, chronic fractures, 1 year f/u

Mechanics of Balloons Moving Bone (16000297-03)

Mechanical and biomechanical explanation of how

the balloons work to reduce VCFs

White Papers

Risk of Subsequent Vertebral Body Compression

Fractures After Balloon Kyphoplasty (16000509-03)

Biomechanical & clinical evidence about risks

assoc w/ sub fx & need for VB ht restoration

Vertebral Body
Height
Restoration

Voggenreiter Spine 2005 (16000616)

Benefits of the IBT for restoring VB height

Gaitanis Eur Spine J 2005 (16000761)

BKP and vertebral height restoration

Meta-analyses

Taylor Spine 2006 (16000752)

Review of BKP & VP safety and efficacy

Hadjipavlou JBJS Br 2005 (16000690)

Review of BKP & VP complications

Cancer-Related
VCFs
16000369-02

Dudeney J Clin Oncol 2002 (16000361)

BKP and multiple myeloma patients

Fourney J Neuro Spine 2003 (16000466)

BKP & VP in bone metastases

Literature Review
Kallmes NEJM 2009

Buchbinder NEJM 2009

Known as the INVEST study (Investigational

Vertebroplasty Safety & Efficacy Trial)

Supported by grants from

ClinicalTrials.gov (NCT00068822)

Supported by grant (R01-AR49373) from

Australian New Zealand Clinical Trials

Registry # ACTRN012605000079640

Multicenter, randomized controlled trial

Multicenter, randomized, double-blind,

placebo-controlled trial

Key authors

http://www.clinicaltrials.gov/ct/show/NCT00068822?order=2

National Institute of Arthritis & Musculoskeletal &

Skin Diseases
Vertebroplasty (VP) vs simulated sham procedure
11 Centers: 5 US, 5 UK, 1 Australia
131 patients: 68 VP, 63 sham
Kallmes (Mayo Clinic, Rochester, MN)
Turner (Univ. of Wash)

Conclusion: improvements in pain and painrelated disability in VP group were similar to

control at 1 month

National Health & Medical Research Council of Australia

Arthritis Australia
Cabrini Education and Research Institute
Cook Australia

Vertebroplasty (VP) vs simulated sham procedure

4 Australian Centers
78 patients: 38 VP, 40 sham
71 at 6 months (35 VP, 36 sham)

Conclusion: no beneficial effect of VP as

compared with sham procedure for painful OVCFs
at 1 week or at 1, 3, or 6 months

16000369-02

Kallmes, et al (NEJM 2009)

Kallmes, et al (NEJM 2009)

Vertebroplasty vs. Sham
Patient inclusion
VCF up to 12 months old, median 18 weeks
Primary endpoint at 4 weeks after Rx
Primary endpoint at 22 weeks after VCF (5 months)
MRI/NM evidence of VCF NOT REQUIRED
Back pain score of 3 or greater (scale of 0-10) required

Patient exclusion
Between groups (VP & Control): Similar improvements for RDQ and Pain
Within each group: Improvements for RDQ & Pain were NOT clinically significant
based on MCID
16000369-02

Retropulsed bone
Inpatients excluded from study

Atypical patient population!

16000369-02

Kallmes, et al (NEJM 2009)

Buchbinder, et al (NEJM 2009)

Vertebroplasty vs. Sham

Other limitations
1813 patients screened. 431 determined to be eligible to participate.
Of these 431, 300 patients refused to participate.
70% refused to participate
Study took over 4 years to complete.
There was a trend toward a higher rate of clinically meaningful
improvement in pain in the VP group vs Sham group
At 3 months 43% of the patients in the Sham group crossed over
to the VP group compared to 12% in the VP group who crossed
over to the Sham group

16000369-02

RMDQ

Pain

Changes within each group (VP and Placebo Sham):

Small improvements in Pain and RMDQ (baseline to 6 months)
Improvements NOT statistically or clinically significant
16000369-02

Buchbinder, et al (NEJM 2009)

Buchbinder, et al (NEJM 2009)

Vertebroplasty vs. Sham

Patient inclusion

Vertebroplasty vs. Sham

Other limitations

VCF up to 12 months old, median 9 weeks

Primary endpoint at 12 weeks after Rx
Primary endpoint at 21 weeks after VCF (5 months)

468 patients screened. 220 determined to be eligible to participate.

Of these 220, 141 patients refused to participate.
65% refused to participate
Randomization took over 4 years to complete.
2 of the 4 participating hospitals withdrew early after 5 patients had
been enrolled at each. 3rd hospital included 15 patients in 4 years.
68% of procedures were performed in 1 hospital by 1 radiologist.
Interventional Radiologists did not evaluate patients, they simply
did the VP or Sham procedure.

Patient exclusion
Retropulsed bone
>90% collapse
Inpatients excluded from study

Atypical patient population!

16000369-02

16000369-02

FREE Study

Kallmes, Buchbinder (NEJM 2009)

Similarities
Large majority of patients treated in both groups had VCFs greater
than 6 weeks old. Both studies had only 26 patients with VCFs
less than 6 weeks old, not enough for statistical analysis.
Control groups received sham procedure which was a
facet/periosteum injection which may have provided pain relief for
symptoms not due to VCF.
Both studies contradict a large body of literature which on average
report mean pain score reduction of 5.7 following vertebroplasty.

FREE STUDY: Fracture Reduction

Evaluation Study
Randomized controlled trial with 2year follow-up, comparing balloon
kyphoplasty (BKP) to non-surgical
management (NSM) for the treatment
of acute painful VCFs

Results of these studies are due to poor patient selection,

improper inclusion/exclusion criteria, and even the
interventional technique itself
16000369-02

16000369-02

FREE Study

FREE Study

1-year results (Wardlaw Lancet 2009)

Adequately powered for primary outcome

Faster pain relief
Quicker return of mobility
Better quality of life
No significant difference in frequency of
adverse events between groups

300 patients (largest RCT investigating

vertebral augmentation in the setting of VCF)
Goal: formulate evidence-based guidelines by
results at 1 month, 1 year, and 2 years
BKP had greater improvements @ 1 month
compared to NSM and improvements
sustained on average through 12 months for
the treatment of acute VCFs

16000369-02

The FREE Study is the only study with level 1

evidence confirming the effectiveness of vertebral
augmentation based on the Society of Interventional
Radiologys reporting standards for evidence-based
medicine. (Radavany JVIR 2009)

16000369-02