《外科护理学》课程阅读资料（英文）骨折 fracture.pdf

The new england journal o f medicine n engl j med 361;6 nejm.org august 6, 2009 569 original article A Randomized Trial of Vertebroplasty for Osteoporotic Spinal Fractures David F. Kallmes, M.D., Bryan A. Comstock, M.S., Patrick J. Heagerty, Ph.D., Judith A. Turner, Ph.D., David J. Wilson, F.R.C.R., Terry H. Diamond, F.R.A.C.P., Richard Edwards, F.R.C.R., Leigh A. Gray, M.S., Lydia Stout, B.S., Sara Owen, M.Sc., William Hollingworth, Ph.D., Basavaraj Ghdoke, M.D., Deborah J. Annesley-Williams, F.R.C.R., Stuart H. Ralston, F.R.C.P., and Jeffrey G. Jarvik, M.D., M.P.H. From the Mayo Clinic, Rochester, MN (D.F.K., L.A.G.); the University of Washington, Seattle (B.A.C., P.J.H., J.A.T., L.S., B.G., J.G.J.); Nuffield Orthopaedic Centre NHS Trust, Oxford (D.J.W., S.O.), Gartnavel General Hospital, Glasgow (R.E.), the University of Bristol, Bristol (W.H.), Nottingham University Hospital NHS Trust, Nottingham (D.J.A.-W.), and Western General Hospital, University of Edinburgh, Edinburgh (S.H.R.) — all in the United Kingdom; and St. George Hospital, University of New South Wales, Sydney (T.H.D.). Address reprint requests to Dr. Kallmes at the Department of Radiology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, or at kallmes.david@ mayo.edu. N Engl J Med 2009;361:569-79. Copyright © 2009 Massachusetts Medical Society. 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 (43% vs. 12%, P<0.001). 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.) The New England Journal of Medicine Downloaded from nejm.org on October 19, 2011. For personal use only. No other uses without permission. Copyright © 2009 Massachusetts Medical Society. All rights reserved

Thr NEW ENGLAND JOURNAL Of MEDICINE PONTANEOUS VERTEBRAL FRACTURES ARE to be less than 1 year old,as indicated by the dura ssociated with nain disahility and death in tion sly had found that a fra patients with osteoporosis.Percutaneous ver-ture duration of up to 1 vear was associated with tebroplasty,the injection of medical cement,or a good response to vertebroplasty.For fractures polymethylmethacrylate (PMMA),into the frac- of uncertain age,an additional requirement wa ured vertebra pain wide ce marrow edem tance as an f ef ar on bor suspi es guidelin the to were evide ral for fractures that have not responded to medical tial retropulsion of bony fragments.con treatment.Typically,the duration of such fractures hip fracture,active infection,uncorrectable bleed ranges from several weeks to several months or ing diatheses,surgery within the previous 60 days longer for fractures that have not hea ed lack of access to a telephone,inability to commu umerous case mall,un nicate in English,and dem blinded, efr mized The prot relieving pain from oste porotic precise mechanism of action remains unknown However,in the absence of blinded,randomized MEASURES At baseline,patients completed the self-report fec dity index s an n th n andomized cont rolled trial,called the and Effic res were rtorme nd at Th Trial ONVESD.we evaluated the efficacy of PMMA focus of this renort is the nrima infusion in vertebroplasty for patients with pain- 1 month.We also describe outcomes at 3.14.and ful osteoporotic compression fractures,as com 90 days.The prespecified primary outcome mea ithout PMMA vere scores on the modified Roland-Morris ents wh had und Disability Que naire (RDQ and patients'ra 9 h in an ngs o e pr mary ourcomes)than those in the res indicating ain)The RDC METHODS ated with back pain and has been shown to be valid,reliable,and responsive to change in severa TIENT: dingastudy olled patients s at f s in the United The on a s nter in Australia The sites We the basis of having an established vertebrop (pos tion ofn e of 30 prop practice for osteoporotic fractures an enthusiastic on the rdo and measures of pain intensity which local principal investigator,and an available re- was the minimal change on each scale that was ds have beer considered to be clinically important.2 a previo scores on the Pa secondary outcome re 2 th an OF 50 ivities of Daily Livine (SOF-ADD three pain ful osteoporotic vertebral compr scale 27 and the furonean ouality of life-5 Di fractures between vertebral levels T4 and L5,in- mensions(EQ-5D)scale2(a generic health-status adequate pain relief with standard medical ther measure.reflecting mobility.self care.activity lim apy,and a cur Laingforpeiniaensrecfe least3on a scale from 0to 10. Fractures need or oplo cations:and 570 N ENGLI MED 361:6 NEIM.ORG AUGUST 6.2000 Downloaded from nejm

The new england journal o f medicine 570 n engl j med 361;6 nejm.org august 6, 2009 S pontaneous vertebral fractures are associated with pain, disability, and death in 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 treatment.1 Typically, the duration of such fractures ranges from several weeks to several months or longer for fractures that have not healed. Numerous case series and several small, unblinded, nonrandomized, controlled studies have suggested the 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, the role of active treatment effects of PMMA versus nonspecific effects remains unknown. In this randomized, controlled trial, called the Investigational Vertebroplasty Safety and Efficacy Trial (INVEST), we evaluated the efficacy of PMMA infusion in vertebroplasty for patients with painful osteoporotic compression fractures, as compared with a simulated procedure without PMMA. We hypothesized that patients who had undergone vertebroplasty would report less pain and back pain–related disability at 1 month (the primary outcomes) than those in the control group. Methods Patients We enrolled patients at five centers in the United States, five centers in the United Kingdom, and one center in Australia. The sites were selected on the basis of having an established vertebroplasty practice for osteoporotic fractures, an enthusiastic local principal investigator, and an available research coordinator. The study methods have been described previously.13 Because initial recruitment was slow, after the first three patients were enrolled, we liberalized the inclusion criteria to an age of 50 years or older, a diagnosis of one to three painful osteoporotic vertebral compression fractures between vertebral levels T4 and L5, inadequate pain relief with standard medical therapy, and a current rating for pain intensity of at least 3 on a scale from 0 to 10. Fractures needed to be less than 1 year old, as indicated by the duration of pain. We previously had found that a fracture duration of up to 1 year was associated with a good response to vertebroplasty.14 For fractures of uncertain age, an additional requirement was marrow edema on magnetic resonance imaging or increased vertebral-body uptake on bone scanning. 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 previous 60 days, lack of access to a telephone, inability to communicate in English, and dementia. The protocol was approved by the institutional review board at each study center. All patients provided written informed consent. Measures At baseline, patients completed the self-report version of the Charlson comorbidity index15 and provided demographic and clinical information. Evaluation measures were performed before randomization and at various times up to 1 year. The focus of this report is the primary outcomes at 1 month. We also describe outcomes at 3, 14, and 90 days. The prespecified primary outcome measures were scores on the modified Roland–Morris Disability Questionnaire (RDQ) and patients’ ratings of average back-pain intensity during the preceding 24 hours (on a scale of 0 to 10, with higher scores indicating more severe pain). The RDQ is widely used to assess physical disability associated with back pain and has been shown to be valid, reliable, and responsive to change in several studies,16-21 including a study of vertebroplasty.22 The modified RDQ23 is scored on a scale of 0 to 23, with higher scores indicating greater physical disability. We present the (post-specified) proportion of patients who had a decrease of 30% or more on the RDQ and measures of pain intensity, which was the minimal change on each scale that was considered to be clinically important.24-26 Prespecified secondary outcomes included scores on the Pain Frequency Index and the Pain Bothersomeness Index,23 the Study of Osteoporotic Fractures–Activities of Daily Living (SOF–ADL) scale,27 and the European Quality of Life–5 Dimensions (EQ–5D) scale28 (a generic health-status measure, reflecting mobility, self-care, activity limitations, pain, and psychological distress); the use of opioid medications; and scores on the Physical The New England Journal of Medicine Downloaded from nejm.org on October 19, 2011. For personal use only. No other uses without permission. Copyright © 2009 Massachusetts Medical Society. All rights reserved

Vertebroplasty for Osteoporotic Spinal Fractures n engl j med 361;6 nejm.org august 6, 2009 571 Component Summary (PCS) and Mental Component Summary (MCS) subscales of the self-administered Medical Outcomes Study 36-Item ShortForm General Health Survey (SF-36), version 2.29 The PCS assesses limitations in self-care and physical, social, and role activities; bodily pain; and perceived health. The MCS provides an indication of psychological distress and social and role disability because of emotional problems. Patients were asked before 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). Study Treatment All vertebroplasty practitioners in the trial were highly experienced, having performed a mean of approximately 250 procedures (range, 50 to 800). Patients were brought to the fluoroscopy suite, where conscious sedation was induced and sterile preparation for surgery was performed. Using fluoroscopic guidance, the practitioner infiltrated the skin and subcutaneous tissues overlying the pedicle of the target vertebra or vertebrae with 1% lidocaine and infiltrated the periosteum of the pedicles with 0.25% bupivacaine. Patients were then randomly assigned to undergo either the full vertebroplasty procedure or the control intervention. 33p9 131 Underwent randomization 1813 Patients were assessed for eligibility 1682 Were excluded 368 Had a tumor 201 Had no compression fracture 111 Had pain level <3/10 104 Had no osteoporosis 102 Had coagulopathy 92 Had dementia 404 Had other exclusion criteria 300 Declined to participate 68 Were assigned to undergo vertebroplasty 68 Underwent vertebroplasty 63 Were assigned to undergo control intervention 63 Underwent control intervention 1 Missed an interview 1 Missed an interview 1 Withdrew 67 Completed 1-mo assessment 1 Underwent crossover intervention at <1 mo 61 Completed 1-mo assessment 2 Underwent crossover intervention at <1 mo 4 Missed an interview 2 Missed an interview 64 Completed 3-mo assessment 8 Underwent crossover intervention at <3 mo 61 Completed 3-mo assessment 27 Underwent crossover intervention at <3 mo AUTHOR: FIGURE: JOB: ISSUE: 4-C H/T RETAKE SIZE ICM CASE EMail Line H/T Combo Revised AUTHOR, PLEASE NOTE: Figure has been redrawn and type has been reset. Please check carefully. REG F Enon 1st 2nd 3rd Kallmes 1 of 3 08-06-09 ARTIST: ts 36106 Figure 1. Enrollment and Outcomes. The single patient in the vertebroplasty group who missed the 1-month assessment completed the 3-month assessment. The two patients in the control group who missed the 1-month assessment also missed the 3-month assessment. The New England Journal of Medicine Downloaded from nejm.org on October 19, 2011. For personal use only. No other uses without permission. Copyright © 2009 Massachusetts Medical Society. All rights reserved

VERTEBROPLASTY FOR OSTEOPOROTIC SPINAL FRACTURES Table1.(Continued.) characteristic Vertetr roup Cor SF-36 scorel 25.3+7.8 25373 44.8+118 415+141 3.040.3 3.140.8 erso meness Index sc 3.10 -5D scorefi 0.54±0.23 SOF-ADL score 10.0±3.6 103±2.8 y15 Scores vities of Daily Living (SOF-ADL)scale range with PMMA reached to the posterior aspect of the ver- groups.The block sizes ranged from 4 to 12 pa- tebral body or ente extraosse s space,such tients and ass e concealed from the as th bralwertet or an e ural or para rc tants mv signments we by h th patient's back were given.and the methacrylate and were then t placed in number d monomer was opened to simulate the odor asso opaque sealed envelopes with a series ofervelope ciated with mixing of PMMA,but the needle was for each study center.The protocol specified that not placed and MMA was not infused.After the study-group assignments should b conceale om all tients and study personn o pe supine pos or th ere told at the time ofc onsent that ny contact with the they would be allowed to cross over to the other blinded data. procedure 1 month or later after the intervention if adequate pain relief was not achieved.Specific STATISTICAL ANALYSIS numerical th sholds of outcome measures were The study initially had a power of more than80 not us ents we to d s in ry and c for the month of0.05. es over to pmeieiernaietherpts on the rdoand a 10- ce an the nain No commercial entity paid for any mate rating after early difficulty in recruitment and a used in the study.Research funds paid for all costs planned interim analysis of the first 90 patients, related to the contro w e reduced the target sample size to 130 pa ent vertebroplasty proced re were Dll with approval nt data ng bo ify t RANDOMIZAT We used stratified blocked randomizatio ord. ing to study center to achieve roughly balanced reduced sample size,the study had a power of more N ENGLJ MED 361:6 NEJM.ORG AUGUST 6,2009 53 The New Engl d Journal of Medicin other us thout permission

Vertebroplasty for Osteoporotic Spinal Fractures n engl j med 361;6 nejm.org august 6, 2009 573 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. After the procedure, both groups of patients were monitored in the supine position for 1 to 2 hours before discharge. Patients were told at the time of consent that they would be allowed to cross over to the other procedure 1 month or later after the intervention if adequate pain relief was not achieved. Specific numerical thresholds of outcome measures were not used for allowance of crossover. Patients were seen in the clinic for the 1-month follow-up visit by a vertebroplasty practitioner to discuss whether to cross over to receive the alternative therapy. No commercial entity paid for any materials used in the study. Research funds paid for all costs related to the control interventions. Costs of the vertebroplasty procedure were billed to insurance. Randomization and Blinding We used stratified, blocked randomization according to study center to achieve roughly balanced groups. The block sizes ranged from 4 to 12 patients, and assignments were concealed from the research assistants involved in recruitment. These assignments were generated by the data coordinating center with the use of a random-number generator and were then placed in numbered, opaque, sealed envelopes, with a series of envelopes for each study center. The protocol specified that study-group assignments should be concealed from all patients and study personnel who performed follow-up assessments for the duration of the study. Only the study statisticians, who did not have any contact with the patients, saw unblinded data. Statistical Analysis The study initially had a power of more than 80% to detect differences in both primary and secondary outcomes in 250 patients, with a two-sided alpha of 0.05, on the basis of a 2.5-point difference on the RDQ and a 1.0-point difference on the pain rating. After early difficulty in recruitment and a planned interim analysis of the first 90 patients, we reduced the target sample size to 130 patients, with approval from the independent data and safety monitoring board. The decision to modify the target enrollment was driven primarily by accrual rates and revised power calculations. With the reduced sample size, the study had a power of more Table 1. (Continued.) Characteristic Vertebroplasty Group (N=68) Control Group (N=63) SF-36 score‖ Physical component 25.3±7.8 25.3±7.3 Mental component 44.8±11.8 41.5±14.1 Pain Frequency Index score** 3.0±0.8 3.1±0.8 Pain Bothersomeness Index score** 2.9±0.7 3.1±0.8 EQ–5D score†† 0.57±0.18 0.54±0.23 SOF–ADL score‡‡ 10.0±3.6 10.3±2.8 * Plus–minus values are means ±SD. † Race was self-reported. ‡ Scores on the comorbidity index range from 0 to 28, with higher scores indicating greater severity.15 § Scores on the Roland–Morris Disability Questionnaire (RDQ) range from 0 to 23, with higher scores indicating more severe disability. ¶ The pain-intensity rating ranges from 0 (no pain) to 10 (worst pain). ‖ Scores on the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36), version 2, range from 0 to 100, with lower scores indicating a worse outcome. ** Scores on the Pain Frequency Index and Pain Bothersomeness Index range from 0 to 4, with higher scores indicating more severe pain. †† Scores on the European Quality of Life–5 Dimensions (EQ–5D) scale range from −0.1 to 1.0, with higher scores indicating a better quality of life. ‡‡ Scores on the Study of Osteoporotic Fractures–Activities of Daily Living (SOF–ADL) scale range from 0 to 18, with higher scores indicating more back-related disability. The New England Journal of Medicine Downloaded from nejm.org on October 19, 2011. For personal use only. No other uses without permission. Copyright © 2009 Massachusetts Medical Society. All rights reserved