BACKGROUND: Percutaneous vertebroplasty remains widely used to treat osteoporotic vertebral fractures although our 2015 Cochrane review did not support its role in routine practice.
OBJECTIVES: To update the available evidence of the benefits and harms of vertebroplasty for treatment of osteoporotic vertebral fractures.
SEARCH METHODS: We updated the search of CENTRAL, MEDLINE and Embase and trial registries to 15 November 2017.
SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials (RCTs) of adults with painful osteoporotic vertebral fractures, comparing vertebroplasty with placebo (sham), usual care, or another intervention. As it is least prone to bias, vertebroplasty compared with placebo was the primary comparison. Major outcomes were mean overall pain, disability, disease-specific and overall health-related quality of life, patient-reported treatment success, new symptomatic vertebral fractures and number of other serious adverse events.
DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane.
MAIN RESULTS: Twenty-one trials were included: five compared vertebroplasty with placebo (541 randomised participants), eight with usual care (1136 randomised participants), seven with kyphoplasty (968 randomised participants) and one compared vertebroplasty with facet joint glucocorticoid injection (217 randomised participants). Trial size varied from 46 to 404 participants, most participants were female, mean age ranged between 62.6 and 81 years, and mean symptom duration varied from a week to more than six months.Four placebo-controlled trials were at low risk of bias and one was possibly susceptible to performance and detection bias. Other trials were at risk of bias for several criteria, most notably due to lack of participant and personnel blinding.Compared with placebo, high- to moderate-quality evidence from five trials indicates that vertebroplasty provides no clinically important benefits with respect to pain, disability, disease-specific or overall quality of life or treatment success at one month. Evidence for quality of life and treatment success was downgraded due to possible imprecision. Evidence was not downgraded for potential publication bias as only one placebo-controlled trial remains unreported. Mean pain (on a scale zero to 10, higher scores indicate more pain) was five points with placebo and 0.7 points better (0.3 better to 1.2 better) with vertebroplasty, an absolute pain reduction of 7% (3% better to 12% better, minimal clinical important difference is 15%) and relative reduction of 10% (4% better to 17% better) (five trials, 535 participants). Mean disability measured by the Roland-Morris Disability Questionnaire (scale range zero to 23, higher scores indicate worse disability) was 14.2 points in the placebo group and 1.5 points better (0.4 better to 2.6 better) in the vertebroplasty group, absolute improvement 7% (2% to 11% better), relative improvement 9% better (2% to 15% better) (four trials, 472 participants).Disease-specific quality of life measured by the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) (scale zero to 100, higher scores indicating worse quality of life) was 62 points in the placebo group and 2.3 points better (1.4 points worse to 6.7 points better), an absolute imrovement of 2% (1% worse to 6% better); relative improvement 4% better (2% worse to 10% better) (three trials, 351 participants). Overall quality of life (European Quality of Life (EQ5D), zero = death to 1 = perfect health, higher scores indicate greater quality of life) was 0.38 points in the placebo group and 0.05 points better (0.01 better to 0.09 better) in the vertebroplasty group, absolute improvement: 5% (1% to 9% better), relative improvement: 18% (4% to 32% better) (three trials, 285 participants). In one trial (78 participants), 9/40 (or 225 per 1000) people perceived that treatment was successful in the placebo group compared with 12/38 (or 315 per 1000; 95% CI 150 to 664) in the vertebroplasty group, RR 1.40 (95% CI 0.67 to 2.95), absolute difference: 9% more reported success (11% fewer to 29% more); relative change: 40% more reported success (33% fewer to 195% more).Low-quality evidence (downgraded due to imprecision and potential for bias from the usual-care controlled trials) indicates uncertainty around the risk estimates of harms with vertebroplasty. The incidence of new symptomatic vertebral fractures (from six trials) was 48/418 (95 per 1000; range 34 to 264)) in the vertebroplasty group compared with 31/422 (73 per 1000) in the control group; RR 1.29 (95% CI 0.46 to 3.62)). The incidence of other serious adverse events (five trials) was 16/408 (34 per 1000, range 18 to 62) in the vertebroplasty group compared with 23/413 (56 per 1000) in the control group; RR 0.61 (95% CI 0.33 to 1.10). Notably, serious adverse events reported with vertebroplasty included osteomyelitis, cord compression, thecal sac injury and respiratory failure.Our subgroup analyses indicate that the effects did not differ according to duration of pain (acute versus subacute). Including data from the eight trials that compared vertebroplasty with usual care in a sensitivity analyses altered the primary results, with all combined analyses displaying considerable heterogeneity.
AUTHORS' CONCLUSIONS: We found high- to moderate-quality evidence that vertebroplasty has little clinical benefit in terms of pain for treating acute or subacute osteoporotic vertebral fractures in routine practice when compared with a sham procedure. Results were consistent across the studies irrespective of the average duration of pain.Sensitivity analyses confirmed that open trials comparing vertebroplasty with usual care are likely to have overestimated any benefit of vertebroplasty. Correcting for these biases would likely drive any benefits observed with vertebroplasty towards the null, in keeping with findings from the placebo-controlled trials.Numerous serious adverse events have been observed following vertebroplasty. However due to the small number of events, we cannot be certain about whether or not vertebroplasty results in a clinically important increased risk of new symptomatic vertebral fractures and/or other serious adverse events. Patients should be informed about both the high- to moderate-quality evidence that shows no important benefit of vertebroplasty and its potential for harm.
BACKGROUND: Surgical and non-surgical interventions are the two categories for treatment of vertebral compression fractures (VCFs). However, there is clinical uncertainty over optimal management. This study aimed to examine the safety and effectiveness of surgical management for treatment of VCFs with osteopenia compared with non-surgical treatment.
METHODS: We conducted a systematic search through electronic databases from inception to June 2014, with no limits on study data or language. Randomized controlled trials (RCTs) evaluating surgical versus non-surgical interventions for treatment of patients with VCFs due to osteopenia were considered. Primary outcomes were pain and adverse effects. A random-effects model was used to calculate the pooled mean difference (MD) or risk ratios with 95% confidence interval (CI).
RESULTS: Sixteen reports (11 studies) met the inclusion criteria, and provided data for the meta-analysis with a total of 1,401 participants. Compared with conservative treatment, surgical treatment was more effective in reducing pain (short-term: MD -2.05, 95% CI -3.55 to -0.56, P=0.007; mid-term: MD -1.70, 95% CI -2.78 to -0.62, P=0.002; long-term: MD -1.24, 95% CI -2.20 to -0.29, P=0.01) and disability on the Roland-Morris Disability score (short-term: MD -4.97, 95% CI -8.71 to -1.23, P=0.009), as well as improving quality of life on the Short-Form 36 Physical Component Summary score (short-term: MD 5.53, 95% CI 1.45 to 9.61, P=0.008) and the Quality of Life Questionnaire of the European Foundation for Osteoporosis score (short-term: MD -5.01, 95% CI -8.11 to -1.91, P=0.002). Indirect comparisons between vertebroplasty and kyphoplasty found no evidence that the treatment effect differed across the two interventions for any outcomes assessed. Compared with the sham procedure, surgical treatment showed no evidence of improvement in pain relief and physical function. Based on these two comparisons, no significant difference between groups was noted in the pooled results for adverse events.
CONCLUSION: Compared to conservative treatment, surgical treatment was more effective in decreasing pain in the short,mid and long terms. However, no significant mid- and long-term differences in physical function and quality of life was observed. Little good evidence is available for surgical treatment compared with that for sham procedure. PV and BK are currently used to treat VCFs with osteopenia, with little difference in treatment effects. Evidence of better quality and from a larger sample size is required before a recommendation can be made.
SYSTEMATIC REVIEW REGISTRATION: http://www.crd.york.ac.uk/PROSPERO PROSPERO registration number: CRD42013005142.
OBJECTIVES: To analyse the impact of placebo effects on outcome in trials of selected minimally invasive procedures and to assess reported adverse events in both trial arms.
DESIGN: A systematic review and meta-analysis.
DATA SOURCES AND STUDY SELECTION: We searched MEDLINE and Cochrane library to identify systematic reviews of musculoskeletal, neurological and cardiac conditions published between January 2009 and January 2014 comparing selected minimally invasive with placebo (sham) procedures. We searched MEDLINE for additional randomised controlled trials published between January 2000 and January 2014.
DATA SYNTHESIS: Effect sizes (ES) in the active and placebo arms in the trials' primary and pooled secondary end points were calculated. Linear regression was used to analyse the association between end points in the active and sham groups. Reported adverse events in both trial arms were registered.
RESULTS: We included 21 trials involving 2519 adult participants. For primary end points, there was a large clinical effect (ES≥0.8) after active treatment in 12 trials and after sham procedures in 11 trials. For secondary end points, 7 and 5 trials showed a large clinical effect. Three trials showed a moderate difference in ES between active treatment and sham on primary end points (ES ≥0.5) but no trials reported a large difference. No trials showed large or moderate differences in ES on pooled secondary end points. Regression analysis of end points in active treatment and sham arms estimated an R(2) of 0.78 for primary and 0.84 for secondary end points. Adverse events after sham were in most cases minor and of short duration.
CONCLUSIONS: The generally small differences in ES between active treatment and sham suggest that non-specific mechanisms, including placebo, are major predictors of the observed effects. Adverse events related to sham procedures were mainly minor and short-lived. Ethical arguments frequently raised against sham-controlled trials were generally not substantiated.
BACKGROUND: Percutaneous vertebroplasty (PVP) is a minimally invasive surgical procedure in which bone cement is injected into a fractured vertebra. Percutaneous balloon kyphoplasty (BKP) is a variation of this approach, in which an inflatable balloon tamp is placed in the collapsed vertebra prior to cement injection. OBJECTIVES: To systematically evaluate and appraise the clinical effectiveness and cost-effectiveness of PVP and percutaneous BKP in reducing pain and disability in people with osteoporotic vertebral compression fractures (VCFs) in England and Wales. DATA SOURCES: A systematic review was carried out. Ten databases including MEDLINE and CINAHL were searched from inception to November 2011, and supplemented by hand-searching relevant articles and contact with an expert. Studies met the inclusion criteria if they were randomised controlled trials (RCTs) including people with painful osteoporotic VCFs with a group receiving PVP or BKP. In addition, lead authors of identified RCTs were contacted for unpublished data. REVIEW METHODS: Primary outcomes were health-related quality of life; back-specific functional status/mobility; pain/analgesic use; vertebral body height and angular deformity; incidence of new vertebral fractures and progression of treated fracture. A manufacturer provided academic-in-confidence observational data indicating that vertebral augmentation may be associated with a beneficial mortality effect, and that, potentially, BKP was more efficacious than PVP. These data were formally critiqued. A mathematical model was constructed to explore the cost-effectiveness of BKP, PVP and operative placebo with local anaesthesia (OPLA) compared with optimal pain management (OPM). Six scenario analyses were conducted that assessed combinations of assumptions on mortality (differential beneficial effects for BKP and PVP; equal beneficial effects for BKP and PVP; and no effect assumed) and derivation of utility data (either mapped from visual analogue scale pain score data produced by a network meta-analysis or using direct European Quality of Life-5 Dimensions data from the trials). Extensive sensitivity analyses were conducted on each of the six scenarios. This report contains reference to confidential information provided as part of the National Institute for Health and Care Excellence appraisal process. This information has been removed from the report and the results, discussions and conclusions of the report do not include the confidential information. These sections are clearly marked in the report. RESULTS: A total of nine RCTs were identified and included in the review of clinical effectiveness. This body of literature was of variable quality, with the two double-blind, OPLA-controlled trials being at the least risk of bias. The most significant methodological issue among the remaining trials was lack of blinding for both study participants and outcome assessors. Broadly speaking, the literature suggests that both PVP and BKP provide substantially greater benefits than OPM in open-label trials. However, in double-blinded trials PVP was shown to have no more benefit than local anaesthetic; no trials of BKP compared with local anaesthesia have been conducted. A formal analysis of observational mortality data undertaken within this report concluded that it was not possible to say with certainty if there is a difference in mortality between patients undergoing BKP and PVP compared with OPM. Results from the cost-effectiveness analyses were varied, with all of BKP, PVP and OPLA appearing the most cost-effective treatment dependent on the assumptions made regarding mortality effects, utility, hospitalisation costs and OPLA costs. LIMITATIONS: Data on key parameters were uncertain and/or potentially confounded, making definitive conclusions difficult to make. CONCLUSION: For people with painful osteoporotic VCFs refractory to analgesic treatment, PVP and BKP perform significantly better in unblinded trials than OPM in terms of improving quality of life and reducing pain and disability. However, there is as yet no convincing evidence that either procedure performs better than OPLA. The uncertainty in the evidence base means that no definitive conclusion on the cost-effectiveness of PVP or BKP can be provided. Further research should focus on establishing whether or not BKP and PVP have a mortality advantage compared with OPLA and on whether or not these provide any utility gain compared with OPLA. STUDY REGISTRATION: This study was registered as PROSPERO number CRD42011001822. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
Cement augmentation is a controversial treatment for painful vertebral compression fractures (VCF). Our research questions for the meta-analysis were: Is there a clinical and statistical difference in pain relief, functional improvement, and quality of life between conservative care and cement augmentation for VCF and, if so, are they maintained at longer time points? We conducted a search of MEDLINE from January 1980 to July 2011 using PubMed, Cochrane Database of Systematic Reviews and Controlled Trials, CINAHL, and EMBASE. Searches were performed from medical subject headings. Terms "vertebroplasty" and "compression fracture" were used. The outcome variables of pain, functional measures, health-related quality of life (HRQOL), and new fracture risk were analyzed. A random effects model was chosen. Continuous variables were calculated using the standardized mean difference comparing improvement from baseline of the experimental group with the control group. New vertebral fracture risk was calculated using log odds ratio. Six studies met the criteria. The pain visual analog scale (VAS) mean difference was 0.73 (confidence interval [CI] 0.35, 1.10) for early (<12 weeks) and 0.58 (CI 0.19, 0.97) for late time points (6 to 12 months), favoring vertebroplasty (p < 0.001). The functional outcomes at early and late time points were statistically significant with 1.08 (CI 0.33, 1.82) and 1.16 (CI 0.14, 2.18), respectively. The HRQOL showed superior results of vertebroplasty compared with conservative care at early and late time points of 0.39 (CI 0.16, 0.62) and 0.33 (CI 0.16, 0.51), respectively. Secondary fractures were not statistically different between the groups, 0.065 (CI -0.57, 0.70). This meta-analysis showed greater pain relief, functional recovery, and health-related quality of life with cement augmentation compared with controls. Cement augmentation results were significant in the early (<12 weeks) and the late time points (6 to 12 months). This meta-analysis provides strong evidence in favor of cement augmentation in the treatment of symptomatic VCF fractures.
BACKGROUND: Osteoporotic vertebral compression fractures (OVCFs) are the most common osteoporotic fractures. Pain is the main symptom. Percutaneous vertebroplasty (PVP) is a therapeutic procedure performed to reduce pain in vertebral compression fractures. Numerous case series and several small, non-blinded, non-randomized controlled studies have suggested that vertebroplasty is an effective means of relieving pain from osteoporotic fractures. However, a recent pooled analysis from 2 multicenter randomized controlled trials concluded that the improvement in pain afforded by PVP was similar to placebo.
OBJECTIVE: To compare the amount of pain reduction measured using the visual analog scale when OVCF is treated with vertebroplasty or conservatively, and assess the clinical utility of PVP.
DESIGN: A meta-analysis and systematic review of randomized controlled trials was performed comparing pain reduction following vertebroplasty and conservative treatment.
LIMITATIONS: There were few data sources from which to extract abstracted data or published studies. There were only 5 randomized controlled trials that met our criteria. The conservative treatments used as comparators in these trials were different.
METHODS: A search of MEDLINE from January 1980 to July 2012 using PubMed, the Cochrane Database of Systematic Reviews and Controlled Trials, CINAHL, and EMBASE. Relevant reports were examined by 2 independent reviewers and the references from these reports were searched for additional trials, using the criteria established in the QUOROM statement.
RESULTS: Pooled results from 5 randomized controlled trials are shown. There was no difference in pain relief in the PVP group at 2 weeks and one month when compared with the conservatively managed group. Pain relief in the PVP group was greater than that of the conservative group at 3 months, 6 months, and 12 months. However, after subgroup analysis, pain scores were similar between the PVP group and the sham injection group from 2 weeks to 6 months. Compared with non-operative therapy, PVP reduced pain at all times studied.
CONCLUSION: PVP has some value for relieving pain; however, the possibility of a placebo effect should be considered. PVP has gained acceptance as a complementary treatment when conservative management has failed before its benefits have been fully understood. More large scale, double blinded, controlled trials are necessary in order to quantify the pain relief afforded by PVP more precisely.
BACKGROUND: Osteoporotic vertebral compressed fractures (VCFs) are the most common osteoporotic fractures. Although percutaneous vertebroplasty (PVP) reportedly relieves pain and improves function, a recent pooled analysis from two multicenter randomized controlled trials concluded the improvement in pain and disability treated with PVP was similar to those with sham surgery.
QUESTIONS/PURPOSE: Using meta-analysis we therefore asked whether compared with either nonoperative therapy or a sham injection for patients with VCF, PVP would (1) better relieve pain, (2) provide greater improvement in pain-related disability, and (3) increase the recurrence of vertebral fractures.
METHODS: We searched PubMed, EMBASE, Medline, and the Cochrane library using the keywords "vertebroplasty AND osteoporosis OR fracture". We included nine of the 469 articles identified. Using a random effects model, we calculated the weighted mean differences to evaluate the pain reduction at different times as the primary outcome. Pain-related disability was assessed by a quality of life (QOL) measure. Improvement of QOL and recurrence of vertebral fractures were the secondary outcomes. We used subgroup analysis to reinvestigate pain relief and function improvement of PVP based on two different controls: nonoperative therapy and sham injection. The total number of patients was 886.
RESULTS: Pain scoring was similar between the PVP group and the sham injection group at 1 to 29 days and 90 days. However, compared with nonoperative therapy, PVP reduced pain at all times studied. QOL in the PVP group was improved or tended to be improved compared with QOL for both control groups. The risk of new fractures was similar between the PVP groups and both control groups.
CONCLUSIONS: Different control groups may have accounted for the different conclusions in the literature regarding the ability of PVP to relieve pain and restore function recovery. Compared with nonoperative treatment PVP relieved pain better and improved QOL. PVP did not increase the risk of new fractures.
LEVEL OF EVIDENCE: Level II, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
After more than two decades the treatment effect of cement augmentation of osteoporotic vertebral compression fractures (VCF) has now been questioned by two blinded randomised placebo-controlled trials. Thus many practitioners are uncertain on the recommendation for cement augmentation techniques in elderly patients with osteoporotic VCF. This systematic review analyses randomised controlled trials on vertebroplasty and kyphoplasty to provide an overview on the current evidence. From an electronic database research 8 studies could be identified meeting our inclusion criteria of osteoporotic VCF in elderly (age>60 years), treatment with vertebroplasty or kyphoplasty, controlled with placebo or standard medical therapy, quality of life, function, or pain as primary parameter, and randomisation. Only two studies were properly blinded using a sham-operation as control. The other studies were using a non-surgical treatment control group. Further possible bias may be caused by manufacturer involvement in financing of three published RCT. There is level Ib evidence that vertebroplasty is no better than placebo, which is conflicting with the available level IIb evidence that there is a positive short-term effect of cement augmentation compared to standard medical therapy with regard to QoL, function and pain. Kyphoplasty is not superior to vertebroplasty with regard to pain, but with regard to VCF reduction (evidence level IIb). Kyphoplasty is probably not cost-effective (evidence level IIb), and vertebroplasty has not more than short-term cost-effectiveness (evidence level IV). Vertebroplasty and kyphoplasty cannot be recommended as standard treatment for osteoporotic VCF. Ongoing sham-controlled trials may provide further evidence in this regard.
Journal»European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society
PURPOSE: To determine if differences in safety or efficacy exist between balloon kyphoplasty (BKP), vertebroplasty (VP) and non-surgical management (NSM) for the treatment of osteoporotic vertebral compression fractures (VCFs).
METHODS: As of February 1, 2011, a PubMed search (key words: kyphoplasty, vertebroplasty) resulted in 1,587 articles out of which 27 met basic selection criteria (prospective multiple-arm studies with cohorts of ≥ 20 patients). This systematic review adheres to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines.
RESULTS: Pain reduction in both BKP (-5.07/10 points, P < 0.01) and VP (-4.55/10, P < 0.01) was superior to that for NSM (-2.17/10), while no difference was found between BKP/VP (P = 0.35). Subsequent fractures occurred more frequently in the NSM group (22 %) compared with VP (11 %, P = 0.04) and BKP (11 %, P = 0.01). BKP resulted in greater kyphosis reduction than VP (4.8º vs. 1.7°, P < 0.01). Quality of life (QOL) improvement showed superiority of BKP over VP (P = 0.04), along with a trend for disability improvement (P = 0.08). Cement extravasation was less frequent in the BKP (P = 0.01). Surgical intervention within the first 7 weeks yielded greater pain reduction than VCFs treated later.
CONCLUSIONS: BKP/VP provided greater pain relief and fewer subsequent fractures than NSM in osteoporotic VCFs. BKP is marginally favored over VP in disability improvement, and significantly favored in QOL improvement. BKP had a lower risk of cement extravasation and resulted in greater kyphosis correction. Despite this analysis being restricted to Level I and II studies, significant heterogeneity suggests that the current literature is delivering inconsistent messages and further trials are needed to delineate confounding variables.
UNLABELLED: OBJECTIVE OF ANALYSIS: The objective of this analysis is to examine the safety and effectiveness of percutaneous vertebroplasty for treatment of osteoporotic vertebral compression fractures (VCFs) compared with conservative treatment.
CLINICAL NEED AND TARGET POPULATION: Osteoporosis and associated fractures are important health issues in ageing populations. Vertebral compression fracture secondary to osteoporosis is a cause of morbidity in older adults. VCFs can affect both genders, but are more common among elderly females and can occur as a result of a fall or a minor trauma. The fracture may occur spontaneously during a simple activity such as picking up an object or rising up from a chair. Pain originating from the fracture site frequently increases with weight bearing. It is most severe during the first few weeks and decreases with rest and inactivity. Traditional treatment of painful VCFs includes bed rest, analgesic use, back bracing and muscle relaxants. The comorbidities associated with VCFs include deep venous thrombosis, acceleration of osteopenea, loss of height, respiratory problems and emotional problems due to chronic pain. Percutaneous vertebroplasty is a minimally invasive surgical procedure that has gained popularity as a new treatment option in the care for these patients. The technique of vertebroplasty was initially developed in France to treat osteolytic metastasis, myeloma, and hemangioma. The indications were further expanded to painful osteoporotic VCFs and subsequently to treatment of asymptomatic VCFs. The mechanism of pain relief, which occurs within minutes to hours after vertebroplasty, is still not known. Pain pathways in the surrounding tissue appear to be altered in response to mechanical, chemical, vascular, and thermal stimuli after the injection of the cement. It has been suggested that mechanisms other than mechanical stabilization of the fracture, such as thermal injury to the nerve endings, results in immediate pain relief.
PERCUTANEOUS VERTEBROPLASTY: Percutaneous vertebroplasty is performed with the patient in prone position and under local or general anesthesia. The procedure involves fluoroscopic imaging to guide the injection of bone cement into the fractured vertebral body to support the fractured bone. After injection of the cement, the patient is placed in supine position for about 1 hour while the cement hardens. Cement leakage is the most frequent complication of vertebroplasty. The leakages may remain asymptomatic or cause symptoms of nerve irritation through compression of nerve roots. There are several reports of pulmonary cement embolism (PCE) following vertebroplasty. In some cases, the PCE may remain asymptomatic. Symptomatic PCE can be recognized by their clinical signs and symptoms such as chest pain, dyspnea, tachypnea, cyanosis, coughing, hemoptysis, dizziness, and sweating.
RESEARCH METHODS: None
LITERATURE SEARCH: A literature search was performed on Feb 9, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2005 to February 9, 2010. Studies were initially reviewed by titles and abstracts. For those studies meeting the eligibility criteria, full-text articles were obtained and reviewed. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with an unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established. Data extraction was carried out by the author.
INCLUSION CRITERIA: None
STUDY DESIGN: Randomized controlled trials (RCTs) comparing vertebroplasty with a control group or other interventions
STUDY POPULATION: Adult patients with osteoporotic vertebral fracturesSTUDY SAMPLE SIZE: Studies included 20 or more patientsEnglish language full-reportsPublished between Jan 1 2005 and Feb 9, 2010(eligible studies identified through the Auto Alert function of the search were also included)
EXCLUSION CRITERIA: Non-randomized studiesStudies on conditions other than VCF (e.g. patients with multiple myeloma or metastatic tumors)Studies focused on surgical techniquesStudies lacking outcome measures RESULTS OF EVIDENCE-BASED ANALYSIS: A systematic search yielded 168 citations. The titles and the abstracts of the citations were reviewed and full text of the identified citations was retrieved for further consideration. Upon review of the full publications and applying the inclusion and exclusion criteria, 5 RCTs were identified. Of these, two compared vertebroplasty with sham procedure, two compared vertebroplasty with conservative treatment, and one compared vertebroplasty with balloon kyphoplasty.
RANDOMIZED CONTROLLED TRIALS: Recently, the results of two blinded randomized placebo-controlled trials of percutaneous vertebroplasty were reported. These trials, providing the highest quality of evidence available to date, do not support the use of vertebroplasty in patients with painful osteoporotic vertebral compression fractures. Based on the results of these trials, vertebroplasty offer no additional benefit over usual care and is not risk free. In these trials the treatment allocation was blinded to the patients and outcome assessors. The control group received a sham procedure simulating vertebroplasty to minimize the effect of expectations and to reduce the potential for bias in self-reporting of outcomes. Both trials applied stringent exclusion criteria so that the results are generalizable to the patient populations that are candidates for vertebroplasty. In both trials vertebroplasty procedures were performed by highly skilled interventionists. Multiple valid outcome measures including pain, physical, mental, and social function were employed to test the between group differences in outcomes. Prior to these two trials, there were two open randomized trials in which vertebroplasty was compared with conservative medical treatment. In the first randomized trial, patients were allowed to cross over to the other arm and had to be stopped after two weeks due to the high numbers of patients crossing over. The other study did not allow cross over and recently published the results of 12 months follow-up. The following is the summary of the results of these 4 trials: Two blinded RCTs on vertebroplasty provide the highest level of evidence available to date. Results of these two trials are supported by findings of an open randomized trial with 12 months follow-up. Blinded RCTs showed: No significant differences in pain scores of patients who received vertebroplasty and patients who received a sham procedure as measured at 3 days, 2 weeks and 1 month in one study and at 1 week, 1 month, 3 months, and 6 months in the other.The observed differences in pain scores between the two groups were neither statistically significant nor clinically important at any time points.The above findings were consistent with the findings of an open RCT in which patients were followed for 12 months. This study showed that improvement in pain was similar between the two groups at 3 months and were sustained to 12 months.In the blinded RCTs, physical, mental, and social functioning were measured at the above time points using 4-5 of the following 7 instruments: RDQ, EQ-5D, SF-36 PCS, SF-36 MCS, AQoL, QUALEFFO, SOF-ADLThere were no significant differences in any of these measures between patients who received vertebroplasty and patients who received a sham procedure at any of the above time points (with a few exceptions in favour of control intervention).These findings were also consistent with the findings of an open RCT which demonstrated no significant between group differences in scores of ED-5Q, SF-36 PCS, SF 36 MCS, DPQ, Barthel, and MMSE which measure physical, mental, and social functioning (with a few exceptions in favour of control intervention).One small (n=34) open RCT with a two week follow-up detected a significantly higher improvement in pain scores at 1 day after the intervention in vertebroplasty group compared with conservative treatment group. However, at 2 weeks follow-up, this difference was smaller and was not statistically significant.Conservative treatment was associated with fewer clinically important complicationsRisk of new VCFs following vertebroplasty was higher than those in conservative treatment but it requires further investigation.
Percutaneous vertebroplasty remains widely used to treat osteoporotic vertebral fractures although our 2015 Cochrane review did not support its role in routine practice.
OBJECTIVES:
To update the available evidence of the benefits and harms of vertebroplasty for treatment of osteoporotic vertebral fractures.
SEARCH METHODS:
We updated the search of CENTRAL, MEDLINE and Embase and trial registries to 15 November 2017.
SELECTION CRITERIA:
We included randomised and quasi-randomised controlled trials (RCTs) of adults with painful osteoporotic vertebral fractures, comparing vertebroplasty with placebo (sham), usual care, or another intervention. As it is least prone to bias, vertebroplasty compared with placebo was the primary comparison. Major outcomes were mean overall pain, disability, disease-specific and overall health-related quality of life, patient-reported treatment success, new symptomatic vertebral fractures and number of other serious adverse events.
DATA COLLECTION AND ANALYSIS:
We used standard methodologic procedures expected by Cochrane.
MAIN RESULTS:
Twenty-one trials were included: five compared vertebroplasty with placebo (541 randomised participants), eight with usual care (1136 randomised participants), seven with kyphoplasty (968 randomised participants) and one compared vertebroplasty with facet joint glucocorticoid injection (217 randomised participants). Trial size varied from 46 to 404 participants, most participants were female, mean age ranged between 62.6 and 81 years, and mean symptom duration varied from a week to more than six months.Four placebo-controlled trials were at low risk of bias and one was possibly susceptible to performance and detection bias. Other trials were at risk of bias for several criteria, most notably due to lack of participant and personnel blinding.Compared with placebo, high- to moderate-quality evidence from five trials indicates that vertebroplasty provides no clinically important benefits with respect to pain, disability, disease-specific or overall quality of life or treatment success at one month. Evidence for quality of life and treatment success was downgraded due to possible imprecision. Evidence was not downgraded for potential publication bias as only one placebo-controlled trial remains unreported. Mean pain (on a scale zero to 10, higher scores indicate more pain) was five points with placebo and 0.7 points better (0.3 better to 1.2 better) with vertebroplasty, an absolute pain reduction of 7% (3% better to 12% better, minimal clinical important difference is 15%) and relative reduction of 10% (4% better to 17% better) (five trials, 535 participants). Mean disability measured by the Roland-Morris Disability Questionnaire (scale range zero to 23, higher scores indicate worse disability) was 14.2 points in the placebo group and 1.5 points better (0.4 better to 2.6 better) in the vertebroplasty group, absolute improvement 7% (2% to 11% better), relative improvement 9% better (2% to 15% better) (four trials, 472 participants).Disease-specific quality of life measured by the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) (scale zero to 100, higher scores indicating worse quality of life) was 62 points in the placebo group and 2.3 points better (1.4 points worse to 6.7 points better), an absolute imrovement of 2% (1% worse to 6% better); relative improvement 4% better (2% worse to 10% better) (three trials, 351 participants). Overall quality of life (European Quality of Life (EQ5D), zero = death to 1 = perfect health, higher scores indicate greater quality of life) was 0.38 points in the placebo group and 0.05 points better (0.01 better to 0.09 better) in the vertebroplasty group, absolute improvement: 5% (1% to 9% better), relative improvement: 18% (4% to 32% better) (three trials, 285 participants). In one trial (78 participants), 9/40 (or 225 per 1000) people perceived that treatment was successful in the placebo group compared with 12/38 (or 315 per 1000; 95% CI 150 to 664) in the vertebroplasty group, RR 1.40 (95% CI 0.67 to 2.95), absolute difference: 9% more reported success (11% fewer to 29% more); relative change: 40% more reported success (33% fewer to 195% more).Low-quality evidence (downgraded due to imprecision and potential for bias from the usual-care controlled trials) indicates uncertainty around the risk estimates of harms with vertebroplasty. The incidence of new symptomatic vertebral fractures (from six trials) was 48/418 (95 per 1000; range 34 to 264)) in the vertebroplasty group compared with 31/422 (73 per 1000) in the control group; RR 1.29 (95% CI 0.46 to 3.62)). The incidence of other serious adverse events (five trials) was 16/408 (34 per 1000, range 18 to 62) in the vertebroplasty group compared with 23/413 (56 per 1000) in the control group; RR 0.61 (95% CI 0.33 to 1.10). Notably, serious adverse events reported with vertebroplasty included osteomyelitis, cord compression, thecal sac injury and respiratory failure.Our subgroup analyses indicate that the effects did not differ according to duration of pain (acute versus subacute). Including data from the eight trials that compared vertebroplasty with usual care in a sensitivity analyses altered the primary results, with all combined analyses displaying considerable heterogeneity.
AUTHORS' CONCLUSIONS:
We found high- to moderate-quality evidence that vertebroplasty has little clinical benefit in terms of pain for treating acute or subacute osteoporotic vertebral fractures in routine practice when compared with a sham procedure. Results were consistent across the studies irrespective of the average duration of pain.Sensitivity analyses confirmed that open trials comparing vertebroplasty with usual care are likely to have overestimated any benefit of vertebroplasty. Correcting for these biases would likely drive any benefits observed with vertebroplasty towards the null, in keeping with findings from the placebo-controlled trials.Numerous serious adverse events have been observed following vertebroplasty. However due to the small number of events, we cannot be certain about whether or not vertebroplasty results in a clinically important increased risk of new symptomatic vertebral fractures and/or other serious adverse events. Patients should be informed about both the high- to moderate-quality evidence that shows no important benefit of vertebroplasty and its potential for harm.
