Accepted Manuscript

New, high quality evidence for vertebroplasty in the management of painful recent
compression fractures: review of the VAPOUR trial and why it should influence
practice

Dr Reade De Leacy, MBBS, BSc, FRANZCR

PII: S1878-8750(16)30869-5
DOI: 10.1016/j.wneu.2016.09.043
Reference: WNEU 4583

To appear in: World Neurosurgery

Please cite this article as: De Leacy R, New, high quality evidence for vertebroplasty in the management
of painful recent compression fractures: review of the VAPOUR trial and why it should influence practice,
World Neurosurgery (2016), doi: 10.1016/j.wneu.2016.09.043.

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 ACCEPTED MANUSCRIPT

New, high quality evidence for vertebroplasty in the management of painful

recent compression fractures: review of the VAPOUR trial and why it should

influence practice.

Dr Reade De Leacy MBBS, BSc, FRANZCR

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The efficacy and safety of vertebroplasty has been extensively debated in the

literature and in clinical practice since the publication of two much publicized

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masked randomized control trials in 2009 in the New England Journal of Medicine

(NEJM). (1,2) Between the advent of vertebroplasty in the mid 1980s, and prior to

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the Kallmes and Buchbinder publications in 2009, the popularity and growth of

percutaneous vertebroplasty was driven by meta-analyses of observational data

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sets and retrospective series. Much has been discussed about the strengths and

legitimate weaknesses of the Kallmes and Buchbinder trials. Despite the significant
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limitations of both trials, they have shaped medical practice since their publication,
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seeing a significant drop in the utilization of vertebroplasty within the United States

and in the case of Australia, resulting in cessation of public funding for the
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procedure. This serves to highlight the significant role that evidence based
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medicine plays in shaping federal health policy and in influencing the distribution of
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health care funding.

A Cochrane Database systematic review from 2015 (3) found, based on moderate

quality evidence, that vertebroplasty for treating osteoporotic fractures was not

supported in routine practice. Regardless, there remained concern from the

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interventional community that the Cochrane recommendation, while being based on

data from two trials with superior methodological quality, largely represented a

patient population that did not accurately reflect the treatment group encountered

in routine clinical practice. A well-reported disparity has been described in the

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outcomes between the two blinded NEJM RCTs that assessed vertebroplasty in

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fractures out to 12 months in duration and a larger, but open-label RCT (4) which

assessed the safety and efficacy of vertebroplasty in painful fractures of less than 6

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weeks age. The latter showed vertebroplasty to be more effective than conservative

care in reducing pain. The discrepancy between these three trials lead to position

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statements endorsing vertebroplasty for osteoporotic compression fractures by the

National Health Service of England and Wales (NHS) and many major international
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medical societies. (5,6) The disparity was well described in the National Institute

for Health and Care Excellence (which directly advises the NHS) providing
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endorsement of vertebroplasty for the treatment of patients who have severe,

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ongoing pain after recent, unhealed vertebral fracture despite optimal pain

management and in whom the pain has been confirmed to be at the level of fracture
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by physical examination and by imaging.

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There is evidence from open label RCTs supporting early intervention for painful

compression fractures that are unresponsive to conservative medical management.

(4,7) William Clark and colleagues recently published their results from the

VAPOUR trial in The Lancet. This methodologically strong trial was specifically

designed to assess the role of vertebroplasty in the painful acute/sub-acute fracture

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population. (8) The VAPOUR trial is a multicenter, randomized, masked, placebo

controlled trial of the safety and efficacy of vertebroplasty for patients with painful

vertebral compression fractures of less than 6 weeks duration. Patients with either

one or two osteoporotic compression fractures of less than 6 weeks duration and

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numeric rated scale (NRS) back pain of greater than or equal to 7 out of 10 were

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eligible for inclusion and randomization. A total of 120 patients were enrolled at

four hospital sites between November 2011 and December 2014. 61 were

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randomized to vertebroplasty and 59 to placebo/sham procedure (subcutaneous

local anesthetic infiltration). The primary outcome was a reduction of NRS score to

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less than 4 at 14 days post procedure. 44% of patients randomized to

vertebroplasty met the primary endpoint (24/61) compared to 21% in the placebo
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arm (12/59) (figure 1). A between-group difference of 23 percentage points was

seen (95% CI 6/39; p=0.011). The treatment advantage persisted throughout

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follow up to 6 months at all time points and a statistically significant reduction in

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Roland-Morris Disability Questionnaire scores between the two groups from 1 to 6

months post procedure. When anatomic subgroup analysis was performed,

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benefits were found to be concentrated in patients with fractures involving the

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thoracolumbar segments (T11 to L2) (see figure 2). The authors postulate that this
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significant difference is secondary to increased biomechanical stress and flexion

load at these levels. In this group 61% (20/33) of patients in the treatment arm

reached the primary endpoint compared to 13% (4/31) in the control group

(difference 48%, 95% CI 27 68). At 6 months 53% (27/51) of patients within the

control/sham group still had moderate or severe pain and 76% (39/51) were still
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using analgesic medication compared to 58% (29/50) in the treatment arm

(difference 18%, CI 1-36; p=0.048).

84 of the 102 patients (41 vertebroplasty and 43 control) who completed the 6-

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month follow up also had baseline and 6 month radiographs available for review.

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The baseline vertebral body height loss was similar in both groups. At 6 months the

authors reported a mean vertebral body height loss of 27% in the treatment group

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compared to 63% in the control group (a difference 36 percentage points, 95% CI

30 43). Three patients in the vertebroplasty group went on to develop single

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interval fractures at a separate level compared to two patients in the control group

who sustained 2 and 5 incident fractures respectively.

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57% of enrolled patients were hospital inpatients. Although a cost effectiveness

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analysis was not performed in VAPOUR, the average length of hospital stay was
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reduces by 5.5 days from 14 days in the control group to 8.5 days in the treatment

group. Such a significant difference would almost certainly result in overall health
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care savings despite the added procedural costs and merits further cost analysis
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studies in the future.

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Three patients in each group died during the study, all judged to be unrelated to the

procedure. The authors reported two serious adverse events related to the

procedure. One patient had a respiratory arrest after administration of sedation,

prior to commencing the procedure. The patient in question was resuscitated and
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underwent the intervention 2 days later without issue. Another patient suffered a

supracondylar humeral fracture in a paretic arm during transfer onto the

procedural table. They report two serious adverse events within the control group

related to the fracture. Both patients developed spinal cord compromise and

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compression secondary to vertebral collapse and compression several weeks

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following enrollment. The authors state that neither fracture had significant

retropulsion of fragments at the time of enrollment. One patient underwent

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neurosurgical decompression with resolution of neurological deficits while the

other, deemed not to be a surgical candidate, became paraplegic. A limitation to the

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trial was that the majority of enrolled patients (85%) came from a single center.

This may limit the extrapolation of their impressive results to smaller, low volume
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practices.
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William Clark et al. have designed and implemented this well-constructed, masked,
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randomized placebo-controlled trial. They have decisively shown vertebroplasty to

be a safe and effective procedure with the most marked benefit identified for
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fractures near the thoracolumbar junction (T11 L2). For inpatients, treatment
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may additionally lead to a significant reduction in overall length of hospital stay and
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therefore a significant reduction in healthcare costs. It is also important to note that

from their results, conservative management is not without risk of significant

adverse event and morbidity.

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The implications of VAPOUR are clear. Patients with severe pain from a recent

vertebral compression fracture, confirmed on physical exam and with magnetic

resonance imaging or single-photon emission computed tomography not responsive

to conservative management should be offered percutaneous vertebroplasty. This

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is in line with the combined standards of practice statement released by the Society

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of Interventional radiology (SIR), American Association of Neurological Surgeons

(AANS) and the Congress of Neurological Surgeons (CNS), American College of

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Radiology (ACR), American Society of Neuroradiology (ASNR), American Society of

Spine Radiology (ASSR), Canadian Interventional Radiology Association (CIRA, and

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the Society of Neurointerventional Surgery (SNIS). (5)
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References
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1. Kallmes DF, Comstock BA, Heagerty PJ, Turner JA, Wilson DJ, Diamond TH, et al.
A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J
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Med. Massachusetts Medical Society; 2009 Aug 6;361(6):56979.

2. Buchbinder R, Osborne RH, Ebeling PR, Wark JD, Mitchell P, Wriedt C, et al. A
randomized trial of vertebroplasty for painful osteoporotic vertebral fractures.
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N Engl J Med. Massachusetts Medical Society; 2009 Aug 6;361(6):55768.

3. Buchbinder R, Golmohammadi K, Johnston RV, Owen RJ, Homik J, Jones A, et al.

Percutaneous vertebroplasty for osteoporotic vertebral compression fracture.
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Buchbinder R, editor. Cochrane Database Syst Rev. Chichester, UK: John Wiley &
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Sons, Ltd; 2015;(4):CD006349.

4. Klazen CAH, Venmans A, de Vries J, van Rooij WJ, Jansen FH, Blonk MC, et al.
Percutaneous vertebroplasty is not a risk factor for new osteoporotic
compression fractures: results from VERTOS II. AJNR Am J Neuroradiol.
American Society of Neuroradiology; 2010 Sep;31(8):144750.

5. Barr JD, Jensen ME, Hirsch JA, McGraw JK, Barr RM, Brook AL, et al. Position
statement on percutaneous vertebral augmentation: a consensus statement
developed by the Society of Interventional Radiology (SIR), American
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Association of Neurological Surgeons (AANS) and the Congress of Neurological

Surgeons (CNS), American College of Radiology (ACR), American Society of
Neuroradiology (ASNR), American Society of Spine Radiology (ASSR), Canadian
Interventional Radiology Association (CIRA), and the Society of
NeuroInterventional Surgery (SNIS). Vol. 25, Journal of vascular and
interventional radiology : JVIR. 2014. pp. 17181.

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6. Chandra RV, Meyers PM, Hirsch JA, Abruzzo T, Eskey CJ, Hussain MS, et al.
Vertebral augmentation: report of the Standards and Guidelines Committee of
the Society of NeuroInterventional Surgery. J Neurointerv Surg. BMJ Publishing

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Group Ltd; 2013 Nov 6;6(1):neurintsurg201301101215.

7. Rousing R, Hansen KL, Andersen MO, Jespersen SM, Thomsen K, Lauritsen JM.

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Twelve-Months Follow-up in Forty-Nine Patients With Acute/Semiacute
Osteoporotic Vertebral Fractures Treated Conservatively or With Percutaneous
Vertebroplasty. Spine. 2010 Mar;35(5):47882.

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8. Clark W, Bird P, Gonski P, Diamond TH, Smerdely P, McNeil HP, et al. Safety and
efficacy of vertebroplasty for acute painful osteoporotic fractures (VAPOUR): a
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multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2016
Aug 17.
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Figures Taken from the article

Figure 1: Proportion of patients in each group with Numeric rated Scale (NRS)

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pain intensity of less than 4 out of 10.
Results are shown for 3 days, 14 days, 1 month, 3 months and 6 months after the
intervention. Vertical bars are 95% CIs. The primary outcome was the proportion

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of patients with an NRS pain score of less than 4 out of 10 at 12 weeks.

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Figure 2: Pre-specified subgroup outcomes

Risk difference (percentage points) of meeting the primary endpoint of a Numeric
Rated Scale pain score less than 4 out of 10, at 14 days after the procedure. Positive

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numbers favor vertebroplasty and negative numbers favor placebo.

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