데이빗 칼메스(David F. Kallmes) 박사의 골시멘트 추체성형술 효과

[메디]

추체성형술 효과에 의문

골다공증성 척추압박골절동통·기능개선에 차이없어

입력 : 2009.11.13 08:44


미국·미네소타주 로체스터-메이요 클리닉 방사선의학과 신경외과학 데이빗 칼메스(David F. Kallmes) 박사는 척추압박골절로 인한 동통완화와 동통 관련 기능부전의 개선은 추체성형술을 받은 환자나 시멘트를 주입하지 않은 모의 추체성형술을 받은 환자나 모두 같다고 New England Journal of Medicine에 발표했다.

추체성형술은 널리 이용되는 수기로서 의료용 시멘트를 척추에 넣어 골다공증성 골절환자의 통증완화와 기능개선에 목적을 두고 있다. 미국립보건원(NIH)이 지원한 이 시험은 이중맹검시험 디자인을 이용해 추체성형술의 효과를 조사한 것으로 관련 시험으로는 처음이다.

 대표연구자인 칼메스 박사는 “의학계는 오랫동안 추체성형술을 실시해 왔지만 치료 효과가 시멘트 주입에 있는지 환자의 기대와 기타 요인 때문인지를 증명한 연구결과는 없었다”고 지적했다. 박사는 또 “시멘트는 영구적인 의료용 임플란트로서 향후 척추골절이 재발할 위험이 있다”고도 설명했다.

미국, 영국, 호주의 8개 의료센터 연구자가 총 131명의 환자를 시험에 등록하고 추체성형술군(68명)과 대조군(63명)으로 나누었다. 치료시작 전의 동통과 기능의 특성에 대해서는 양쪽군에 차이가 없었다. 치료기간 중 양쪽군에서 비슷하게 기능 및 동통이 개선됐다. 추적조사는 지금도 계속되고 있으며 조만간 결과가 보고될 예정이다.박사는 “추체성형술에 전혀 효과가 없다는 것은 아니다. 효과는 분명히 있다. 그러나 시멘트 주입의 유무에 관계없이 양쪽군 모두 시술 후 1개월에 통증과 기능이 크게 개선됐다. 이는 국소마취와 진정제, 환자의 기대, 기타 요인 덕분일 가능성이 있다”고 설명하고 “환자는 치료 선택지를 결정하기 전에 의학적인 어드바이스를 의료관계자와 상담해야 한다”고 강조했다.박사에 따르면 메이요클리닉에서는 관련 연구 프로젝트가 일부 진행 중이며 그 중에는 풍선을 이용해 시멘트 주입 공간을 메우는 풍선 추체성형술(kyphoplasty)의 연구와 동통에 대한 국소마취 효과를 측정하는 비맹검시험 등이 있다.

 

골시멘트 수술 1개월 후의 결과는 골시멘트를 하든 안하든 비슷하다는 내용입니다. 최소 1개월 이상의 보존적치료를 해 보고 나서 골시멘트를 할 건지 안 할건지 선택하셔도 좋을 듯합니다. 물론 보존적치료에 있어서 보조기는 필수입니다. 
실제로 문의전화 오시는 분 중에 척추체성형술을 했는데도 불구하고 통증이 있다고 호소하시는 분들이 늘고 있습니다.
스피노메드는 기존의 보조기 보다 우수한 결과가 나오고 있습니다
비용적인 측면에서도 (건강보험 적용이 안될때) 골시멘트 수술은 200여만원 이상입니다.

(스피노메드는 1/4의 비용의 수준입니다)



척추체성형술을 받으면 통증도 빨리 없어질 것이고
빨리 집으로 돌아갈 수 있을 것이다.
빨리 다 나을 수 있을 것이다 라고 기대하거나
병원에서 하라는대로 하는 것이 정답일 것이다 라는 기대감 또는 조급함 때문인가요?
척추체성형술은 신중하게 고려해 보셔야 합니다!!!!!

우선 골다공증성 척추압박골절은 보존적치료가 우선적으로 시행되어야 합니다

우리나라 건강보험심사평가원 지침은 2주~3주 정도의 적극적인 보존적치료를

행하고서도 별다른 반응이 없을 때,

척추체성형술 또는 풍선척추체성형술을 시행하여도 좋다고 지침을 내리고 있으며

또 그렇게 해야만 건강보험 적용을 받을 수 있도록 하고 있습니다.

하지만 보존적 치료라는 것이 2~3주만에 효과를 거두기는 사실상 불가능합니다.

뼈의 골절은 기본적으로 4주 이상의 보존적치료,

즉, 발이나 손 등의 골절의 경우 4~6주간 깁스를 해야 뼈가 붙는다는 것은 일반인도 알 수 있는 내용입니다.

척추뼈 골절도 최소 4~6주 이상의 보존적치료가 시행되어야 효과를 볼 수 있지 않을까요?

더구나 골다공증이 있는 노인들의 경우는 최소 4~주이상의 좀 더 적극적인 보존적치료를 시행해야됩니다. 

하지만 병원에서는 2주 정도의 침상안정과 약물치료(통증약)와 보조기의 사용,  그 후 척추체성형술(골시멘트), 풍선척추 성형술(풍선을 이용한 골시멘트)을 하자고 하는 것은

결국 보존적치료는 형식적으로 하고 모두가 척추체성형술을 할 수 밖에 없는 구조입니다.

제도개선이 필요하다고 생각됩니다.

최근 보도에 따르면 우리나라 척추관련 수술은 미국도 많다고 하는데 미국에 비해 4배 이상, 유럽에 비해 9~12배 이상 많다고 합니다.

 

N Engl J Med. 2009 Aug 6;361(6):569-79. doi: 10.1056/NEJMoa0900563.

A randomized trial of vertebroplasty for osteoporotic spinal fractures.

Kallmes DF1, Comstock BA, Heagerty PJ, Turner JA, Wilson DJ, Diamond TH, Edwards R, Gray LA, Stout L, Owen S, Hollingworth W, Ghdoke B, Annesley-Williams DJ, Ralston SH, Jarvik JG.<p></p></p>

 

Author information

¹Department of Radiology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA. kallmes.david@mayo.edu

 

Erratum in

N Engl J Med. 2012 Mar 8;366(10):970.

Abstract 

BACKGROUND:

Vertebroplasty is commonly used to treat painful, osteoporotic vertebral compression fractures

 

METHODS:

In this multicenter trial, we randomly assigned 131 patients who had one to three painful osteoporotic vertebral compression fractures to undergo either vertebroplasty or a simulated procedure without cement (control group). The primary outcomes were scores on the modified Roland-Morris Disability Questionnaire (RDQ) (on a scale of 0 to 23, with higher scores indicating greater disability) and patients' ratings of average pain intensity during the preceding 24 hours at 1 month (on a scale of 0 to 10, with higher scores indicating more severe pain). Patients were allowed to cross over to the other study group after 1 month.

 

RESULTS:

All patients underwent the assigned intervention (68 vertebroplasties and 63 simulated procedures). The baseline characteristics were similar in the two groups. At 1 month, there was no significant difference between the vertebroplasty group and the control group in either the RDQ score (difference, 0.7; 95% confidence interval [CI], -1.3 to 2.8; P=0.49) or the pain rating (difference, 0.7; 95% CI, -0.3 to 1.7; P=0.19). Both groups had immediate improvement in disability and pain scores after the intervention. Although the two groups did not differ significantly on any secondary outcome measure at 1 month, there was a trend toward a higher rate of clinically meaningful improvement in pain (a 30% decrease from baseline) in the vertebroplasty group (64% vs. 48%, P=0.06). At 3 months, there was a higher crossover rate in the control group than in the vertebroplasty group (51% vs. 13%, P<0.001) [corrected]. There was one serious adverse event in each group.

 

CONCLUSIONS:

Improvements in pain and pain-related disability associated with osteoporotic compression fractures in patients treated with vertebroplasty were similar to the improvements in a control group. (ClinicalTrials.gov number, NCT00068822.)

2009 Massachusetts Medical Society

 

Comment in

[Randomized vertebroplasty trials in the management of painful osteoporotic vertebral compression fractures]. [J Radiol. 2009]

Vertebroplasty trials: the medium is the message. [J Vasc Interv Radiol. 2014]

Trials of vertebroplasty for vertebral fractures. [N Engl J Med. 2009]

Balancing science and informed choice in decisions about vertebroplasty. [N Engl J Med. 2009]

Vertebroplasty for osteoporotic fracture? Think twice. [J Fam Pract. 2009]

Evidence-based recommendations for spine surgery. [Spine (Phila Pa 1976). 2010]

Trials of vertebroplasty for vertebral fractures. [N Engl J Med. 2009]

Trials of vertebroplasty for vertebral fractures. [N Engl J Med. 2009]

Trials of vertebroplasty for vertebral fractures. [N Engl J Med. 2009]

ACP Journal Club. Vertebroplasty was not effective for painful osteoporotic vertebral fractures. [Ann Intern Med. 2009]

 

N Engl J Med. Author manuscript; available in PMC 2010 Aug 31.Published in final edited form as

N Engl J Med. 2009 Aug 6; 361(6): 569–579. 10.1056/NEJMoa0900563

 

 

A Randomized Controlled Trial of Vertebroplasty for Osteoporotic Spine Fractures

D.F. Kallmes,¹ B.A. Comstock,² P.J. Heagerty,² J.A. Turner, Ph.D.,² D.J. Wilson,⁴ T.H. Diamond,⁵ R. Edwards,⁶ L.A. Gray,¹ L. Stout,² S. Owen,⁴ W. Hollingworth,³ B. Ghdoke,² D.J. Annesley-Williams,⁷ S.H. Ralston,⁸ and J.G. Jarvik²

¹ Mayo Clinic, Rochester, MN/US

University of Washington, Seattle, WA/US³ Department of Social Medicine, Bristol/UK⁴ Nuffield Orthopaedic Centre NHS Trust, Oxford/UK

 St George Hospital, University of New South Wales, Sydney/AU<⁶ Gartnavel General Hospital, Glasgow/UK⁷ Nottingham University Hospital NHS Trust, Nottingham/UK<⁸ Western General Hospital, University of Edinburgh, Edinburgh/UK

Corresponding author: David F. Kallmes, MD, Mayo Clinic, Department of Neurointerventional Radiology, 200 First Street, SW, Rochester, MN 55905, Email: ude.oyam@divad.semllak, Telephone: 507-266-3350, Fax: 507-255-0706

Author information ► Copyright and License information ►

 

Copyright notice and Disclaimer

 

The publisher's final edited version of this article is available at N Engl J Med

See commentary "Rules vs. Statistics: Insights from a Highly Inflected Language" in Cogn Sci, volume 35 on page 638.

See commentary "Development of target-specific treatments in multiple myeloma" in Br J Haematol, volume 151 on page 3.

See commentary "Cognitive, Behavioral, and Functional Consequences of Inadequate Sleep in Children and Adolescents" in Pediatr Clin North Am, volume 58 on page 649.

See commentary "Essais randomisés de la vertébroplastie pour le traitement de la douleur des fractures vertébrales par insuffisance osseuse." in J Radiol, volume 90 on page 1785.

See commentary "Trials of vertebroplasty for vertebral fractures." in N Engl J Med, volume 361 on page 2098.

See commentary "Balancing science and informed choice in decisions about vertebroplasty." in N Engl J Med, volume 361 on page 619.

See commentary "Trials of vertebroplasty for vertebral fractures." in N Engl J Med, volume 361 on page 2097.

See commentary "Trials of vertebroplasty for vertebral fractures." in N Engl J Med, volume 361 on page 2098.

See commentary "Trials of vertebroplasty for vertebral fractures." in N Engl J Med, volume 361 on page 2098.This article has been corrected.

See the correction in volume 366 on page 970

See other articles in PMC that cite the published article.

 

 

Abstract

Background

Vertebroplasty is used commonly to treat painful, osteoporotic vertebral compression fractures.

 

Methods

In this multi-center trial, we randomly assigned patients with 1-3 painful, osteoporotic vertebral compression fractures to vertebroplasty or to a simulated vertebroplasty without cement. The primary outcomes were modified Roland-Morris Disability Questionnaire (RDQ) scores (range, 0–23) and patient ratings of average pain intensity in the preceding 24 hours (0–10 numerical rating scale) at one month. Patients were allowed to cross over after one month.

 

Results

All patients received their assigned interventions (68 vertebroplasty and 63 simulated vertebroplasty). The baseline characteristics were similar in the two groups. At one month, the vertebroplasty and control groups did not differ significantly on either the RDQ (treatment difference: 0.7; 95% CI: −1.3, 2.8; P = 0.49) or the pain rating (treatment difference: 0.7; 95% CI: −0.3, 1.7; P = 0.19). Both groups showed immediate improvement in disability and pain after the intervention. Although the groups did not differ significantly on any secondary outcome at one month, there was a trend toward a higher rate of clinically meaningful improvement in pain (30% decrease from baseline) in the vertebroplasty group (64% versus 48%, P = 0.06). At three months, there was a higher crossover rate in the control group (43% versus 12%, P<0.001)). There was one serious adverse event in each group.</p>

Conclusions

Improvement in osteoporotic compression fracture pain and pain-related disability was similar in patients treated with vertebroplasty and patients treated with simulated vertebroplasty without cement.</p>

 

Introduction

Spontaneous, painful vertebral fractures represent an important cause of morbidity and mortality among patients with osteoporosis. Percutaneous vertebroplasty, the injection of medical cement, or polymethylmethacrylate (PMMA), into the fractured vertebral body has gained widespread acceptance as an effective method of pain relief and has become routine therapy for osteoporotic vertebral fractures. Guidelines recommend vertebroplasty for fractures that have not responded to medical management;¹ typically, such fracture duration ranges from several weeks to several months, or longer, for fractures that have not healed.</p><p id="P6">Numerous case series and several small, non-blinded, non-randomized controlled studies have suggested effectiveness of vertebroplasty in relieving pain from osteoporotic fractures. ^2–12 The precise mechanism of action remains unknown. However, in the absence of blinded, randomized controlled trials (RCTs), the role of active treatment effects of PMMA versus nonspecific effects remains unknown.</p><p class="p p-last" id="P7">We conducted an RCT, the INvestigational Vertebroplasty Safety and Efficacy Trial (INVEST), to eval‎uate the efficacy of PMMA infusion in vertebroplasty for patients with painful, osteoporotic compression fractures, as compared with a simulated vertebroplasty without PMMA. We hypothesized that patients assigned to vertebroplasty, as compared with patients assigned to the control procedure, would report less pain and back pain-related disability at one month (the primary endpoints).</p>

 

Methods

Patients

We enrolled patients from five centers in the U.S., five centers in the United Kingdom, and one center in Australia. Sites were selected based on having an established vertebroplasty practice for osteoporotic fractures, enthusiasm of the local principal investigator, and the availability of a research coordinator. Study methods were described previously. ¹³ Because initial recruitment was slow, after enrolling the first 3 patients, we liberalized our inclusion criteria to: age 50 years or older; 1–3 painful, osteoporotic vertebral compression fractures between vertebral levels T4 and L5; inadequate pain relief with standard medical therapy; and current pain intensity rated at least 3 on a 0–10 scale. Fractures needed to be less than one year old, (as indicated by pain duration); we previously found that fracture duration, up to one year, was not associated with vertebroplasty response.¹⁴ Exclusion criteria were evidence or suspicion of neoplasm in the target vertebral body, substantial retropulsion of bony fragments, concomitant hip fracture, active infection, uncorrectable bleeding diatheses, surgery within the past 60 days, no access to a telephone, inability to communicate in English, and dementia. We required subjects with fractures of uncertain age to have marrow edema on magnetic resonance imaging or increased vertebral body uptake on bone scan. The protocol was approved by the Institutional Review Boards at all sites and all patients gave written informed consent.</p>

 

Measures

At baseline, patients completed the self-report version of the Charlson comorbidity index ¹⁵ and provided demographic and clinical information. Eval‎uation measures were administered prior to randomization and at various times up to one year. The focus of this report is on outcomes at one month, the primary endpoint. We also describe outcomes at three, 14, and 90 days. The pre-specified primary outcome measures were the modified Roland-Morris Disability Questionnaire (RDQ) and a numerical rating scale (NRS; 0 = ‘no pain’ to 10 = ‘pain as bad as could be’) score of average back pain intensity in the preceding 24 hours. The RDQ is widely used to assess physical disability associated with back pain, and has been demonstrated to be valid, reliable, and responsive to change, ^16–21 including in studies of vertebroplasty.²² The modified RDQ ²³ is scored on a 0–23 scale, with higher scores indicating greater physical disability. We present the (post-specified) proportion of patients who achieved a decrease of 30% on the RDQ and NRS measures of pain intensity, the minimal change on each scale considered to be clinically important. ^24–26Pre-specified secondary outcomes included the Pain Frequency and Bothersomeness Scale,²³ the Study of Osteoporotic Fractures -Activities of Daily Living (SOF-ADL),²⁸ the EQ-5D²⁹ (a generic health status measure reflecting mobility, self-care, activity limitations, pain, and psychological distress), opioid medication use, and the Physical Component Summary (PCS) and Mental Component Summary (MCS) subscales of the self-administered SF-36 (version 2).²⁷ The PCS assesses limitations in self-care, physical, social and role activities, bodily pain, and poor perceived health, while MCS provides indication of psychological distress and social and role disability due to emotional problems. Patients were asked prior to discharge on the day of the procedure and at each follow-up assessment to guess which procedure they had undergone and to rate their confidence in their guess on a scale from 0 = ‘no confidence’ to 10 = ‘complete confidence’.</p>

Study Treatment

All vertebroplasty practitioners in the trial were highly experienced, having performed a mean of approximately 250 procedures (range, 50–800 procedures). Patients were brought to the fluoroscopy suite, administered conscious sedation, and prepared in sterile fashion. Using fluoroscopic guidance, the skin and subcutaneous tissues overlying the pedicle of the target vertebra or vertebrae were infiltrated with 1% lidocaine and the periosteum of the pedicle/s was infiltrated with 0.25% bupivicaine. Patients were then randomized to the full vertebroplasty procedure or to the control intervention.</p><p id="P12">For the vertebroplasty procedure, 11- or 13-gauge needles were passed into the central aspect of the target vertebra or vertebrae. Barium-opacified PMMA was prepared on the bench and infused under constant lateral fluoroscopy into the vertebral body. Infusion was stopped when the PMMA reached to the posterior aspect of the vertebral body or entered an extraosseous space, such as the intervertebral disk or an epidural or paravertebral vein.³⁰ During the control intervention, verbal and physical cues, such as pressure on the patient’s back, were given and the methacrylate monomer was opened to simulate the odor associated with mixing of PMMA, but the needle was not placed and PMMA was not infused. Both groups of patients were maintained at bedrest for 1–2 hours prior to discharge.</p><p class="p p-last" id="P13">Patients were told at the time of consent that they would be allowed to cross over to the other procedure one month or later after the intervention if adequate pain relief was not achieved. Specific numerical thresholds of outcome measures were not utilized for allowance of crossover. Patients were seen in clinic at one month by a vertebroplasty practitioner to discuss whether to cross over.</p>

Randomization and Blinding

We used stratified, blocked randomization by clinical site to achieve roughly balanced groups. The block sizes varied between four and 12 patients and were concealed from the research assistants involved in recruitment. These assignments were generated by the data coordinating center (DCC) using a random number generator and then placed in numbered, opaque, sealed envelopes, using a series of envelopes for each study site. We attempted to blind all patients and study personnel performing follow-up assessments to treatment assignments for the duration of the study. Only the study statisticians, who did not have any contact with study participants, saw unblinded data.</p>

Sample Size

The study was conservatively powered initially to detect differences in both primary and secondary outcome measures (initial N = 250 subjects, two-sided alpha = 0.05, power > 80%, 2.5 point difference on Roland, 1.0 point difference on pain rating). After early difficulty in recruitment and planned interim analysis of the first 90 subjects, we revised our target sample size to 130 randomized subjects with approval from the study data and safety monitoring board (DSMB). The decision to modify the target enrollment was driven primarily by accrual rates and revised power calculations. With the reduced sample size, the study remains powered (>80%) to detect important differences in the primary outcome measures: a 3.0-point difference between groups on the RDQ (assumed SD = 6.7) and a 1.5-point difference on the pain rating (assumed SD = 2.7) at one month.²⁶</p>

 

Statistical Analysis

For our primary analyses, we used an “intention-to-treat” strategy with patients analyzed in their assigned group. Treatment effects and confidence intervals were calculated from analysis of covariance (ANCOVA) models adjusting for baseline values of the outcome measure, recruitment site, and a treatment indicator as the predictor of interest. As a post-hoc analysis, we also used logistic regression models, adjusting for site and baseline values of the outcome measures, to compare the proportion of patients in each group who achieved at least a 30% improvement in RDQ and pain scores, as recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials- II to assess the clinical importance of improvement.³¹ Further, we performed two post hoc subgroup analyses to determine whether continuous and categorical (1–13, 14–26, and 27–52 weeks) measures of baseline pain duration (as an index of fracture age) interacted with treatment in predicting one-month pain intensity in the ANCOVA models. Formal eval‎uation of effect modification is based on a partial F-test of whether the 2 interaction terms equal zero. Inference was similar for each subgroup analysis and we report the results of the categorical subgroup analysis.</p><p id="P17">An independent DSMB reviewed the blinded study results every six months to eval‎uate safety and efficacy. The DSMB monitored events of death, paralysis, hospitalizations, new onset fractures, new radiculopathy or myelopathy, and infection. The DSMB used O’Brien-Fleming ³² stopping rules of P < 0.001 and P < 0.019 for two pre-specified interim analyses to eval‎uate the accumulating evidence for treatment efficacy, though the interim study results did not achieve either threshold. All statistical analyses were performed using R statistical software (version 2.7) ³³ and primary pre-specified one-month outcomes were considered significant at P < 0.043. All reported P-values are two-sided and not adjusted for multiple testing.</p><p class="p p-last" id="P18">The study was conceived by Drs. Kallmes and Jarvik, with subsequent design input from Drs. Heagerty, Hollingworth, and Turner and Mr. Comstock. The data were gathered by coordinators at each study site and sent to the DCC for quality control and analysis. Dr. Heagerty and Mr. Comstock performed the data analyses. Drs. Heagerty and Jarvik and Mr. Comstock vouch for the data and analysis. Dr. Kallmes wrote the initial draft with substantial contributions from the co-authors.</p>

 

Results

Between June 2004 and August 2008, 131 patients were enrolled and randomized (Fig. 1). Sixty-eight patients were randomized to vertebroplasty and 63 to the control intervention; all received the allocated intervention. The baseline characteristics of the groups were similar (Table 1). One patient (1%) in the vertebroplasty group and two patients (3%) in the control group were lost to follow-up prior to one month. One patient (1%) in the vertebroplasty group and two patients (3%) in the control group crossed over prior to one month.</p><div class="fig iconblock ten_col whole_rhythm clearfix" id="F1" co-legend-rid="lgnd_F1">

Figure 1

Enrollment, Randomization, and Follow-up of the Study Participants.

Table 1

Baseline Characteristics of Study Participants.

The vertebroplasty and control groups did not differ significantly on either pre-specified primary outcomes of RDQ (treatment difference: 0.7; 95% CI, −1.3 to 2.8; P=0.49) or pain intensity (treatment difference: 0.7; 95% CI, −0.3 to 1.7; P=0.19) at one month (Table 2). Both groups showed substantial improvement in their back-related disability and pain immediately (three days) after the procedure, with comparable improvement between groups. The improvement in each group at three days was maintained at one month.</p><div class="table-wrap iconblock ten_col ">

Table 2

Treatment Comparisons on Primary Outcomes (Intent-to-Treat analyses).

The treatment groups did not differ significantly on any of the secondary outcomes, including measures of pain and quality of life, at one month (Fig. 2). Further, the groups did not differ in the post-specified proportion of patients achieving clinically meaningful improvement in back pain-related physical disability at one month (40% of vertebroplasty patients vs. 41% of control intervention patients, P=0.99). There was a trend (P=0.06) toward a higher rate of clinically meaningful improvement in pain in the vertebroplasty group (64%) versus the control group (48%).</p><div class="fig iconblock ten_col whole_rhythm clearfix" i">

Figure 2

Treatment Comparisons on Secondary Outcome Measures (Intent-to-Treat Analyses) at One Month.

By three months, 8 (12%) patients in the vertebroplasty group and 27 (43%) patients in the control group crossed over to the other group (P<0.001). The vertebroplasty patients who crossed over reported higher disability and pain at three and 14 days, as compared with the other patients (Fig. 3). Control intervention patients who crossed over showed some early improvement after the control procedure that disappeared by the one-month assessment. However, even after they received the alternative intervention, neither the control nor the vertebroplasty patients who crossed over improved by three months to the extent of non-crossover subjects.

Figure 3

Mean (95% confidence intervals) Roland-Morris Disability Questionnaire (RDQ) and pain numerical rating scores (average pain intensity, prior 24 hours) by treatment adherence over time. Treatment “crossover” was defined as having had the ...

At 14 days, 63% of patients in the control group correctly guessed they had the control intervention, and 51% of patients in the vertebroplasty group correctly guessed they had the vertebroplasty. Both groups expressed similarly moderate confidence in their treatment guess on average (vertebroplasty mean=4.0, control mean=4.1; P=0.78). In the control group, 18 of 33 (55%) patients who adhered to treatment correctly guessed at 14 days that they had received the control intervention compared to 20 of 27 (74%) who eventually crossed over (P=0.12). Notably, among the eight vertebroplasty patients who crossed over to the control intervention, six (75%) guessed incorrectly at one month that they had received the control intervention.</p><p class="p" id="P24">In a post hoc subgroup analysis, the effect of treatment (vertebroplasty vs. control procedure) on one-month pain did not differ significantly across the three baseline pain duration categories (partial F-test P=0.58, 2 degrees of freedom). The treatment effect for patients with less than 13 weeks of pain (treatment difference: 0.8; 95% CI, −0.8 to 2.4; P=0.31) was similar to the results of the overall analysis. The treatment effect for patients with 14 – 26 weeks of pain was 1.3 (95% CI, −0.8 to 3.4; P=0.23) and that for patients with 27 – 52 weeks of pain was 0.0 (95% CI, −1.7 to 1.6; P=0.96).</p>

Adverse events

One patient in the vertebroplasty group suffered injury to the thecal sac during the procedure, with resultant hospitalization. One patient in the control intervention group was hospitalized overnight after the procedure with tachycardia and rigors, of unclear etiology.</p>

 

Discussion

Patients with osteoporotic vertebral fractures who were randomly assigned to either a full vertebroplasty or a control intervention consisting of a simulated vertebroplasty without infusion of PMMA did not differ significantly one month after the procedure on measures of back pain intensity, functional disability, and quality of life. In this study the confidence interval for the effect on RDQ is (−1.3, 2.8) which excludes a treatment benefit of 3 points or greater and therefore provides evidence against clinically meaningful treatment effects on functional disability. Similarly the confidence interval for the pain rating treatment effect is (−0.3, 1.7) which excludes effects of 2 points or greater. Both treatment groups showed immediate improvement in pain and disability after the procedure, and this improvement was sustained at one month. These results suggest that factors separate from instillation of PMMA may account for the observed clinical improvement following vertebroplasty. Such factors may include the impact of local anesthesia as well as nonspecific effects such as expectations of pain relief (“placebo effect”), natural history, and regression toward the mean.</p><p id="P27">The impact of the placebo effect on outcomes in this trial remain unclear. Previous studies have documented pain reduction in placebo trials, on the order of 6–7mm on a 100mm scale^34–36. The treatment effect in our trial was substantially larger than these previous reports, although those reports included pharmacologic and psychological interventions in addition to physical interventions³⁴.</p><p id="P28">The vertebroplasty group showed a trend towards a higher proportion of patients with clinically meaningful improvement in pain at one month. Further, there was a higher crossover rate in the control group than in the vertebroplasty group after one month. The reasons for the higher crossover rate are unknown. It is possible that more patients in the control group than in the vertebroplasty group had unsatisfactory pain outcomes, but that we were unable to detect this with our measure of pain intensity. However, we used a common, validated measure demonstrated to show responsiveness to clinical improvement. It is possible that vertebroplasty was more effective than the control intervention for a subgroup of patients; further research is needed to explore this possibility. Finally, it is possible that despite efforts to prevent this, some patients became unblinded and among the unblinded patients, those who still had pain and learned they were in the control group elected to cross over to vertebroplasty.</p><p id="P29">This study has several limitations. First, because of reluctance of both physicians and patients to accept a control intervention arm for a longer time period, we allowed crossover at one month. This complicates interpretations of group differences in outcome after one month. However, there is evidence that nearly all the benefits of vertebral augmentation accrue within the first month. ³⁷ Additionally, given that the half-life of bupivicaine is only three hours, any benefit from bupivicaine would have disappeared by one month. Second, we did not compare groups on other medical treatments received that might have affected patient outcomes. Third, persistence of pain after vertebroplasty or fracture healing may indicate etiologies for the pain other than fracture, a possibility that our baseline imaging excludes to a certain extent, but not entirely. Fourth, consistent with our previous findings that fracture age was not associated with response to vertebroplasty¹⁴, in this study we did not find a differential treatment effect according to baseline duration of pain, yet it remains possible that vertebroplasty may be effective only for fractures of a certain age or healing stage. Lastly, we limited our study to vertebroplasty and did not eval‎uate the efficacy of Kyphoplasty, which is similar to vertebroplasty except that intraosseous balloons are inflated prior to cement infusion. ³⁸="

In conclusion, at least up to one month, clinical improvement in patients suffering from painful, osteoporotic vertebral fractures is similar between patients treated with vertebroplasty and those treated with a simulated vertebroplasty, without infusion of PMMA. These data suggest that further studies should be undertaken to determine whether long-term outcome is similar between groups, especially because our crossover study design limits the ability of this study to shed light on long-term efficacy of vertebroplasty.</p>

 

Acknowledgments

Arash Etheshami Rad, MD, Mayo Clinic; Tom Marshall, MD and Clare Darrah, Norwich, UK; Avery Evans, MD and Selene Boutin, UVA; Juan Tejada, MD and Vijay Bharati, Indiana University; Andy DeNardo, MD and Judy Jackson, Indianapolis Methodist Hospital; Jonas Goldstein, MD, Asheville, NC

This study was funded by NIH NIAMS R01AR49373

 

Footnotes

Financial Disclosure

Dr. Kallmes receives research support from Arthrocare, Inc., Cardinal Health, Inc., Cook, Inc, and Stryker, Inc. He was a consultant to Bone Support from November, 2007 to November, 2008.

ClinicalTrials.gov NCT00068822

 

References

1. McGraw JK, Cardella J, Barr JD, et al. Society of Interventional Radiology quality improvement guidelines for percutaneous vertebroplasty. J Vasc Interv Radiol. 2003;14(7):827–31. [PubMed]

2. Alvarez L, Alcaraz M, Perez-Higueras A, et al. Percutaneous vertebroplasty: functional improvement in patients with osteoporotic compression fractures. Spine. 2006;31(10):1113–8. [PubMed

3. Diamond TH, Bryant C, Browne L, Clark WA. Clinical outcomes after acute osteoporotic vertebral fractures: a 2-year non-randomised trial comparing percutaneous vertebroplasty with conservative therapy. Med J Aust. 2006;184(3):113–7. [PubMed

4. Diamond TH, Champion B, Clark WA. Management of acute osteoporotic vertebral fractures: a nonrandomized trial comparing percutaneous vertebroplasty with conservative therapy. Am J Med. 2003;114(4):257–65. [PubMed

5. Do HM, Kim BS, Marcellus ML, Curtis L, Marks MP. Prospective analysis of clinical outcomes after percutaneous vertebroplasty for painful osteoporotic vertebral body fractures. AJNR Am J Neuroradiol. 2005;26(7):1623–8. [PubMed

6. Kobayashi K, Shimoyama K, Nakamura K, Murata K. Percutaneous vertebroplasty immediately relieves pain of osteoporotic vertebral compression fractures and prevents prolonged immobilization of patients. Eur Radiol. 2005;15(2):360–7. [PubMed

7. Layton KF, Thielen KR, Koch CA, et al. Vertebroplasty, first 1000 levels of a single center: eval‎uation of the outcomes and complications. AJNR Am J Neuroradiol. 2007;28(4):683–9. [PubMed

8. McGraw JK, Lippert JA, Minkus KD, Rami PM, Davis TM, Budzik RF. Prospective eval‎uation of pain relief in 100 patients undergoing percutaneous vertebroplasty: results and follow-up. J Vasc Interv Radiol. 2002;13(9 Pt 1):883–6. [PubMed

9. Peh WC, Gilula LA, Peck DD. Percutaneous vertebroplasty for severe osteoporotic vertebral body compression fractures. Radiology. 2002;223(1):121–6. [PubMed

10. Voormolen MH, Lohle PN, Lampmann LE, et al. Prospective clinical follow-up after percutaneous vertebroplasty in patients with painful osteoporotic vertebral compression fractures. J Vasc Interv Radiol. 2006;17(8):1313–20. [PubMed

11. Voormolen MH, Mali WP, Lohle PN, et al. Percutaneous vertebroplasty compared with optimal pain medication treatment: short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures. The VERTOS study. AJNR Am J Neuroradiol. 2007;28(3):555–60. [PubMed

12. Zoarski GH, Snow P, Olan WJ, et al. Percutaneous vertebroplasty for osteoporotic compression fractures: quantitative prospective eval‎uation of long-term outcomes. J Vasc Interv Radiol. 2002;13(2 Pt 1):139–48. [PubMed

13. Gray LA, Jarvik JG, Heagerty PJ, et al. INvestigational Vertebroplasty Efficacy and Safety Trial (INVEST): a randomized controlled trial of percutaneous vertebroplasty. BMC Musculoskelet Disord. 2007;8:126. [PMC free article] [PubMed

14. Kaufmann TJ, Jensen ME, Schweickert PA, Marx WF, Kallmes DF. Age of fracture and clinical outcomes of percutaneous vertebroplasty. AJNR Am J Neuroradiol. 2001;22(10):1860–3. [PubMed

15. Katz JN, Chang LC, Sangha O, Fossel AH, Bates DW. Can comorbidity be measured by questionnaire rather than medical record review? Med Care. 1996;34(1):73–84. [PubMed

16. Roland M, Morris R. A study of the natural history of back pain. Part 1: Development of a reliable and sensitive measure of disability in low-back pain. Spine. 1983;8(2):141–4. [PubMed

17. Deyo RA. Comparative validity of the Sickness Impact Profile and shorter scales for functional assessment in low-back pain. Spine. 1986;11:951–4. [PubMed

18. Jensen MP, Strom SE, Turner JA, Romano JM. Validity of the Sickness Impact Profile Roland Scale as a measure of dysfunction in chronic pain patients. Pain. 1992;50:157–62. [PubMed

19. Underwood MR, Barnett AG, Vickers MR. Eval‎uation of two time-specific back pain outcome measures. Spine. 1999;24:1104–12. [PubMed

20. Beurskens AJHM, de Vet HCW, Koke AJA. Responsiveness of functional status in low back pain: a comparison of different instruments. Pain. 1996;65:71–6. [PubMed

21. Roland M, Fairbank J. The Roland-Morris Disability Questionnaire and the Oswestry Disability Questionnaire. Spine. 2000;25:3115–24. [PubMed

22. Trout AT, Kallmes DF, Gray LA, et al. Eval‎uation of vertebroplasty with a validated outcome measure: the Roland-Morris Disability Questionnaire. AJNR Am J Neuroradiol. 2005;26(10):2652–7. [PubMed

23. Patrick DL, Deyo RA, Atlas SJ, Singer DE, Chapin A, Keller RB. Assessing health-related quality of life in patients with sciatica. Spine. 1995;20(17):1899–909. [PubMed

24. Dworkin RH, Turk DC, Wyrwich KW, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain. 2008;9:105–21. [PubMed

25. Farrar JT, Young JP, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001;94:149–58. [PubMed

26. Ostelo RWJG, Deyo RA, Stratford P, et al. Interpreting change scores for pain and functional status in low back pain. Spine. 2008;33:90–4. [PubMed

27. Ware JE, Kosinski M, Dewey JE. How to score version two of the SF-36 health survey. Lincoln, RI: QualityMetric Incorporated; 2000.

28. Ettinger B, Black DM, Nevitt MC, et al. Contribution of vertebral deformities to chronic back pain and disability. The Study of Osteoporotic Fractures Research Group. J Bone Miner Res. 1992;7(4):449–56. [PubMed]

29. Brooks R. EuroQol: the current state of play. Health Policy. 1996;37:53–72. [PubMed

 

30. Jensen ME, Evans AJ, Mathis JM, Kallmes DF, Cloft HJ, Dion JE. Percutaneous polymethylmethacrylate vertebroplasty in the treatment of osteoporotic vertebral body compression fractures: technical aspects. AJNR Am J Neuroradiol. 1997;18(10):1897–904. [PubMed="ref-cit-blk half_rhythm" id="R31">

31. Dworkin RH, Turk DC, Farrar JT, et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005;113(1–2):9–19. [PubMed

32. O’Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics. 1979;35(3):549–56. [PubMed

33. Team RDC. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2008.

34. Hrobjartsson A, Gotzsche PC. Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. N Engl J Med. 2001;344(21):1594–602. [PubMed]

35. Hrobjartsson A, Gotzsche PC. Is the placebo powerless? Update of a systematic review with 52 new randomized trials comparing placebo with no treatment. J Intern Med. 2004;256(2):91–100. [PubMed]

36. Vase L, Riley JL, 3rd, Price DD. A comparison of placebo effects in clinical analgesic trials versus studies of placebo analgesia. Pain. 2002;99(3):443–52. [PubMed]

37. Wardlaw D, Cummings SR, Van Meirhaeghe J, et al. Efficacy and safety of balloon kyphoplasty compared with non-surgical care for vertebral compression fracture (FREE): a randomised controlled trial. Lancet. 2009 [PubMed]

38. Taylor RS, Fritzell P, Taylor RJ. Balloon kyphoplasty in the management of vertebral compression fractures: an updated systematic review and meta-analysis. Eur Spine J. 2007;16(8):1085–100. [PMC free article] [PubMed]

 

 

Randomized controlled trial of vertebroplasty versus kyphoplasty in the treatment of vertebral compression fractures.

Evans AJ¹, Kip KE², Brinjikji W³, Layton KF⁴, Jensen ML¹, Gaughen JR¹, Kallmes DF³.

Author information

• ¹University of Virginia, Charlottesville, Virginia, USA.
• ²University of South Florida, Tampa, Florida, USA.
• ³Mayo Clinic, Rochester, Minnesota, USA.
• ⁴Baylor University Medical Center, Dallas, Texas, USA.

Abstract

BACKGROUND:

<abstracttext label="BACKGROUND" nlmcategory="BACKGROUND">We present the results of a randomized controlled trial eval‎uating the efficacy of vertebroplasty versus kyphoplasty in treating vertebral body compression fractures.</abstracttext>

METHODS:

<abstracttext label="METHODS" nlmcategory="METHODS">Patients with vertebral body compression fractures were randomly assigned to treatment with kyphoplasty or vertebroplasty. Primary endpoints were pain (0-10 scale) and disability assessed using the Roland-Morris Disability Questionnaire (RMDQ). Outcomes were assessed at 3 days, 1 month, 6 months, and 1 year following the procedure.</abstracttext>

RESULTS:

<abstracttext label="RESULTS" nlmcategory="RESULTS">115 subjects were enrolled in the trial with 59 (51.3%) randomly assigned to kyphoplasty and 56 (48.7%) assigned to vertebroplasty. Mean (SD) pain scores at baseline, 3 days, 30 days, and 1 year for kyphoplasty versus vertebroplasty were 7.4 (1.9) vs 7.9 (2.0), 4.1 (2.8) vs 3.7 (3.0), 3.4 (2.5) vs 3.6 (2.9), and 3.0 (2.8) vs 2.3 (2.6), respectively (p>0.05 at all time points). Mean (SD) RMDQ scores at baseline, 3 days, 30 days, 180 days, and 1 year were 17.3 (6.6) vs 16.3 (7.4), 11.8 (7.9) vs 10.9 (8.2), 8.6 (7.2) vs 8.8 (8.5), 7.9 (7.4) vs 7.3 (7.7), 7.5 (7.2) vs 6.7 (8.0), respectively (p>0.05 at all time points). For baseline to 12-month assessment in average pain and RMDQ scores, the standardized effect size between kyphoplasty and vertebroplasty was small at -0.36 (95% CI -1.02 to 0.31) and -0.04 (95% CI -1.68 to 1.60), respectively.</abstracttext>

CONCLUSIONS:

<abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">Our study indicates that vertebroplasty and kyphoplasty appear to be equally effective in substantially reducing pain and disability in patients with vertebral body compression fractures.</abstracttext>

TRIAL REGISTRATION NUMBER:

NCT00279877.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

KEYWORDS:

Balloon; Spine

J Neurointerv Surg. 2015 May 11. pii: neurintsurg-2015-011714. doi: 10.1136/neurintsurg-2015-011714. [Epub ahead of print]

 

Outcomes of vertebroplasty compared with kyphoplasty: a systematic review and meta-analysis.

Gu CN¹, Brinjikji W¹, Evans AJ², Murad MH³, Kallmes DF⁴.

Author information

• ¹Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
• ²Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, Virginia, USA.
• ³Center for Science of Healthcare Delivery, Mayo Clinic, Rochester, Minnesota, USA.
• ⁴Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota, USA.

Abstract

BACKGROUND AND PURPOSE:

<abstracttext label="BACKGROUND AND PURPOSE" nlmcategory="OBJECTIVE">Many studies demonstrate that both kyphoplasty and vertebroplasty are superior to conservative therapy in the treatment of osteoporotic vertebral body compression fractures. We performed a systematic review and meta-analysis of studies comparing the outcomes of vertebroplasty and kyphoplasty, which included prospective non-randomized, retrospective comparative, and randomized studies.</abstracttext>

MATERIALS AND METHODS:

<abstracttext label="MATERIALS AND METHODS" nlmcategory="METHODS">We searched MEDLINE, EMBASE, and the Web of Science databases for studies of kyphoplasty versus vertebroplasty from 1 January 1990 to 30 November 2014 and compared the following outcomes: procedure characteristics, pain and disability improvement, complications and anatomic outcomes. A subgroup analysis was performed comparing pain outcomes based on the risk of bias.</abstracttext>

RESULTS:

<abstracttext label="RESULTS" nlmcategory="RESULTS">29 studies enrolling 2838 patients (1384 kyphoplasty and 1454 vertebroplasty) were included. 16 prospective non-randomized studies, 10 retrospective comparative studies, and 3 randomized controlled studies were included. No significant differences were found in mean pain scores between the two groups postoperatively (2.9±1.5 kyphoplasty vs 2.9±1.7 vertebroplasty, p=0.39) and at 12 months (2.7±1.8 kyphoplasty vs 3.2±1.8 vertebroplasty, p=0.64). No significant differences were found in disability postoperatively (34.7±7.1 kyphoplasty group vs 36.3±7.8 vertebroplasty group, p=0.74) or at 12 months (28.3±16 kyphoplasty group vs 29.6±13.9 vertebroplasty group, p=0.70). Kyphoplasty was associated with lower odds of new fractures (p=0.06), less extraosseous cement leakage (p<0.01), and greater reduction in kyphotic angle (p<0.01).</abstracttext>

CONCLUSIONS:

<abstracttext label="CONCLUSIONS" nlmcategory="CONCLUSIONS">No significant difference was found between vertebroplasty and kyphoplasty in short- and long-term pain and disability outcomes. Further studies are needed to better determine if any particular subgroups of patients would benefit more from vertebroplasty or kyphoplasty in the treatment of vertebral body compression fractures.</abstracttext>

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.