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A meta-analysis of balloon kyphoplasty compared to percutaneous vertebroplasty for treating osteoporotic vertebral compression fractures
Journal of Clinical Neuroscience 20 (2013) 795–803
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Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
A meta-analysis of balloon kyphoplasty compared to percutaneous vertebroplasty for treating osteoporotic vertebral compression fractures Dan Xing a,b, , Jian-Xiong Ma a, , Xin-Long Ma a,c,⇑, Jie Wang a, Wei-Guo Xu c, Yang Chen c, Dong-Hui Song b a
Department of Orthopaedics, Tianjin Medical University General Hospital, 154 Anshan Street, Heping District, Tianjin 300052, China Department of Orthopaedics, Tianjin Gongan Hospital, Heping District, Tianjin, China c Department of Orthopaedics Institute, Tianjin Hospital, Hexi District, Tianjin, China b
a r t i c l e
i n f o
Article history: Received 29 March 2012 Accepted 27 May 2012
Keywords: Kyphoplasty Meta-analysis Osteoporosis Vertebral compression fracture Vertebroplasty
a b s t r a c t A meta-analysis was conducted to assess the safety and efficacy of balloon kyphoplasty (KP) compared to percutaneous vertebroplasty (VP) in the treatment of osteoporotic vertebral compression fractures (OVCF). Ten studies, encompassing 783 patients, met the inclusion criteria. Overall, the results of the meta-analysis indicated that there were significant differences between the two groups in the long-term kyphosis angle (mean difference [MD] = –2.64, 95% confidence interval [CI] = –4.66 to –0.61; p = 0.01), the anterior height of the vertebral body (MD = 3.67, 95% CI = 1.40 to 5.94; p = 0.002), and the cement leakage rates (risk ratio [RR] = 0.70, 95% CI = 0.52 to 0.95; p = 0.02). However, there were no significant differences in the short-term visual analog scale (VAS) scores (MD = –0.57, 95% CI –1.33 to 0.20; p = 0.15), the longterm VAS scores (MD = –0.99, 95% CI = –2.29 to 0.31; p = 0.14), the short-term Oswestry Disability Index (ODI) scores (MD = –6.54, 95% CI = –14.57 to 1.48; p = 0.11), the long-term ODI scores (MD = –2.01, 95% CI = –11.75 to 7.73; p = 0.69), the operation time (MD = 4.47, 95% CI = –0.22 to 9.17; p = 0.06), the short-term kyphosis angle (MD = –2.25, 95% CI = –5.14 to 0.65; p = 0.13), or the adjacent-level fracture rates (RR = 1.52, 95% CI = 0.76 to 3.03; p = 0.24). This meta-analysis demonstrates that KP and VP are both safe and effective surgical procedures for treating OVCF. Compared with VP, KP can significantly relieve a long-term kyphosis angle, improve the height of the vertebral body, and reduce the incidence of bone cement leakage. However, because of the limitations of this meta-analysis, a large randomized controlled trial is required to confirm our findings. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction Osteoporotic vertebral compression fractures (OVCF) are a significant health problem worldwide. These fractures result from a decrease in the anterior vertebral height and cause spinal deformity, reduced pulmonary function, restriction of the abdominal and thoracic contents, impaired mobility, and clinical depression. Conservative management cannot reverse the kyphotic deformity that causes the biomechanical changes in the spinal segment. Biomechanical changes may be one factor leading to an increased incidence of adjacent vertebral fractures. Vertebroplasty (VP) was introduced in 1984, and first described for the treatment of a hemangioma at the C2 vertebra. Since then, VP has been used for the treatment of vertebral compression fractures caused by myeloma, trauma, and osteoporosis. The new surgical technique, kyphoplasty (KP), was conceived and developed by ⇑ Corresponding author. Tel./fax: +86 22 60362062.
E-mail address: [email protected] (X.-L. Ma). These authors contributed equally to this work.
0967-5868/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jocn.2012.05.038
Dr Mark A. Reiley (Berkeley, CA, USA). Both of these surgical techniques not only increase bone strength but also alleviate the pain caused by OVCF. However, KP also seeks to restore the height of the vertebral body. Recently, two randomized controlled trials (RCT) indicated that each of these procedures achieves immediate pain relief unlike conservative treatments.1,2 Last year, Boonen et al.3 published the results of an RCT with a 24-month followup and reported that compared with non-surgical therapy, KP rapidly reduces pain and improves function, mobility, and quality of life, without increasing the risk of additional vertebral fractures. In a review article, Boonen et al.4 reported that VP and KP are generally safe procedures that provide faster pain relief and mobility recovery and, in some cases, vertebral height restoration than conservative management in the short-term. A previous meta-analysis recommended VP over KP for treating OVCF when considering the higher cost of the KP procedure.5 However, which of these two surgical procedures leads to better short-term and long-term outcomes remains controversial. Although few RCT have been conducted, several prospective comparative studies have been published. The purpose of this
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2. Materials and methods
fractures and bone cement leakage. In addition, we defined the short-term time point as no more than 1 week and the long-term time point as more than 6 months. If there were no reported data at those time points, when pooling data we used data from the time point closest to those times..
2.1. Search strategy
2.7. Assessment of methodological quality
To assemble all of the relevant literature, PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)compliant searches of MEDLINE, Embase, ScienceDirect, Ovid, and the Cochrane Central Register of Controlled Trials (CENTRAL) were performed on all peer-reviewed studies published until the end of May 2012 for RCT and prospective comparative studies comparing KP and VP in patients with OVCF. The following search terms were adopted for the database research: kyphoplasty, vertebral compression fracture, osteoporosis, and vertebroplasty. Secondary searches of unpublished literature were conducted by searching the World Health Organization’s International Clinical Trials Registry Platform, the UK National Research Register Archive, and Current Controlled Trials from their inception to March 1, 2012.
The risk of bias in the included studies was independently assessed by two authors (D.X. and X.-L.M.), in accordance with the Cochrane Handbook for Systematic Reviews of Interventions, version 5.0.6 A third author (J.W.) was the adjudicator when no consensus was achieved. We applied the ‘‘assessing the risk of bias’’ table, which includes the following key domains: adequate sequence generation, allocation of concealment, blinding, incomplete outcome data, freedom from selective reporting, and freedom from other biases.
meta-analysis is to evaluate the entire evidence base from RCT and prospective comparative studies to compare the efficacy and safety of KP and VP for patients with OVCF.
2.2. Inclusion criteria Studies were considered eligible for inclusion if they met the following criteria: study design, RCT or prospective comparative studies; population, patients with vertebral compression fractures of osteoporotic etiology; intervention, KP; and comparator, VP. In addition, the studies had to report at least one of the following outcomes: operation time, subjective pain perception, quality of life evaluation, adjacent vertebral fracture incidence, bone cement leakage, vertebral body height, and kyphosis angle post-operation. 2.3. Exclusion criteria Patients were excluded from the meta-analysis if they had a neoplastic etiology (i.e., metastasis or myeloma), an infection, neural compression, a traumatic fracture, a neurological deficit, or spinal stenosis. Other exclusion criteria were severe degenerative diseases of the spine, previous surgery at the involved vertebral body, and KP or VP with other invasive or semi-invasive intervention therapies.
2.8. Data synthesis and analysis We performed all meta-analyses with Review Manager software (RevMan Version 5.1; The Nordic Cochrane Center, The Cochrane Collaboration, Copenhagen, Denmark). For continuous outcomes, means and standard deviations were pooled to a mean difference (MD) and a 95% confidence interval (CI). For dichotomous outcomes, the risk ratio (RR) and the 95% CI were assessed. A probability of p < 0.05 was regarded as statistically significant. The assessment for statistical heterogeneity was calculated using the chi-square and I-square tests. The source of heterogeneity was investigated by a subgroup analysis and a sensitivity analysis. In this meta-analysis, the subgroup analysis was performed according to the short-term and long-term time points during the follow-up. The sensitivity analysis was performed by rejecting the study with the higher statistical heterogeneity. 3. Results 3.1. Search results
Two reviewers (D.X. and J.-X.M.) independently screened the title and abstract related to the eligibility criteria. Then, full-text intensive reading was performed when those studies might meet the inclusion criteria, and the literature was reviewed to determine the final inclusions. We resolved disagreements by discussion to reach a consensus.
A total of 231 titles and abstracts were reviewed, of which 10 studies7–16 eventually satisfied the eligibility criteria. One multicenter, prospective RCT that compared the short- and long-term safety and effectiveness of KP and VP in the treatment of OVCF has been completed but has not yet been published (ClinicalTrials.gov identifier, NCT00323609). Such trials that had recently been completed or were in recruitment but had no published data were excluded from the present study. Therefore, this study included one RCT11 and nine prospective comparative studies7–10,12–16 (Fig. 1). The funnel plot of the incidence of bone cement leakage demonstrated limited evidence of a small study exclusion and publication bias, given the asymmetric diagram with a few studies plotted on the left side of the funnel (Fig. 2).
2.5. Data extraction
3.2. Quality assessment
Two authors (D.X. and J.-X.M.) independently extracted the following data: study characteristics, types of interventions, numbers of vertebral bodies, surgical procedures, and outcome parameters. The extracted data were rechecked by X.-L.M.
Of the 10 included studies, only one study, the RCT,11 had a low risk of bias, and the other nine studies, the prospective comparative studies,7–10,12–16 had a high risk of bias. Only one trial11 reported an adequate generation of the allocation sequence, and two trials10,11 reported allocation concealment. Three studies10,11,16 reported a single-blinding to outcome assessors, and none reported double-blinding; seven others did not mention the blinding method. The methodological quality of the included studies is illustrated in Fig. 3. Judgments about each risk-of-bias item are presented as percentages across all of the included studies in Fig. 4.
2.4. Study selection
2.6. Outcomes The clinical outcomes included the visual analog scale (VAS), the Oswestry Disability Index (ODI), and the operation time. Radiographic outcomes included the kyphosis angle and the anterior vertebral body height. Complication outcomes were adjacent
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Fig. 1. Summary of the study selection and exclusion process.
One of the 10 studies7 included patients with a collapse P15% of the vertebral height and a VAS P5 but excluded those with a collapse P50% of the vertebral height and a local kyphotic deformity P30°. Movrin et al.9 recruited patients with a collapse 690% of the vertebral height. Two of the included studies10,12 only recruited patients with fresh OVCF of the A1 and A3 fracture types.17 Only Schofer et al.12 defined fresh fractures; they included fractures up to 28 days after the causative event. Only one study, the RCT,11 recruited patients with a thoraco-lumbar junction (T12–L1) OVCF. Santiago et al.16 recruited patients with none of the known causes of osteoporosis (such as corticosteroid therapy, inflammatory spondylo-arthropathy and diabetes mellitus). Patients in four of the included studies7,11–13 had only one vertebral fracture. The demographic characteristics of the included studies are summarized in Table 1. Fig. 2. Funnel plot to assess publication bias for the most frequently reported outcome: cement leakage rates. RR = risk ratio, SE = standard error. The asymmetrical funnel plot means publication bias could have existed in this meta-analysis of balloon kyphoplasty compared to percutaneous vertebroplasty for treating osteoporotic vertebral compression fractures.
3.3. Demographic characteristics One RCT and nine prospective comparative studies, consisting of 219 males and 564 females, were eligible for inclusion, with the individual sample size ranging from 45 to 154 patients. Three hundred and seventeen patients underwent KP, and 466 underwent VP. All of the included studies had defined eligibility criteria.
3.4. Outcomes analysis 3.4.1. Clinical outcomes The pain measured by the VAS was classified into short-term and long-term follow-up. We pooled the outcome values according to the subgroup analysis. Seven studies7–12,14 reported the VAS scores at short-term follow-up; there was no significant difference between KP and VP for heterogeneity (MD = –0.57, 95% CI = –1.33 to 0.20; p = 0.15). Long-term VAS scores were available for nine studies;8–16 the pooled results demonstrated no significant difference between KP and VP (MD = –0.99, 95% CI = –2.29 to 0.31; p = 0.14) (Fig. 5). In the five studies8,10,14–16 that provided ODI data, the subgroup analysis was performed according to short-term or long-term
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the meta-analysis, the subgroup and sensitivity analyses could not be performed. 3.4.2. Radiographic outcomes Six studies7,9–12 reported the kyphosis angle after operation. A subgroup analysis was performed, according to short-term and long-term follow-up. Three studies9,10,12 provided data on the short-term kyphosis angle after surgery. Our pooled results showed no significant differences between KP and VP (MD = –2.25, 95% CI = –5.14 to 0.65; p = 0.13). Four trials7,10–12 reported the longterm postoperative kyphosis angle. Patients who underwent KP had a better kyphosis angle than patients who underwent VP (MD = –2.64, 95% CI = –4.66 to –0.61; p = 0.01) (Fig. 8). The sensitivity analysis identified the trial reported by Rollinghoff et al.10 as contributing to the heterogeneity of the outcome. In the four studies10,11,13,16 that reported the postoperative anterior height of the vertebral body, there was a significant difference between the KP and VP groups (MD = 3.67, 95% CI = 1.40 to 5.94; p = 0.002) (Fig. 9). Therefore, patients who underwent KP had a better anterior height of the vertebral body than those who underwent VP. 3.4.3. Complication outcomes Nine studies7–10,12–16 reported complications related to cement leakage. The pooled analysis showed a significantly lower rate of bone cement leakage in the KP group (RR = 0.70, 95% CI = 0.52 to 0.95; p = 0.02) (Fig. 10). In the seven studies8–12,14,15 that provided information about adjacent vertebral compression fractures, there was no significant difference between the KP and VP groups (RR = 1.52, 95% CI = 0.76 to 3.03; p = 0.24) (Fig. 11).
4. Discussion
Fig. 3. Methodological quality of included studies showing the the risk-of-bias of each study in this meta-analysis of balloon kyphoplasty compared to percutaneous vertebroplasty for treating osteoporotic vertebral compression fractures.
follow-up. Two studies8,10 reported the short-term ODI scores. There was no significant difference between the KP and VP groups (MD = –6.54, 95% CI = –14.57 to 1.48; p = 0.11). For the five trials8,10,14–16 that provided long-term ODI data, there was also no significant difference between KP and VP (MD = –2.01, 95% CI –11.75 to 7.73; p = 0.69) (Fig. 6). Statistical evidence of heterogeneity was indicated, and the sensitivity analysis showed that the heterogeneity of outcomes could be attributed to the study reported by Kumar et al.8 The dates of the operation were available for two trials.11,13 The pooled results showed no significant difference between the KP and VP groups (MD = 4.47, 95% CI = –0.22 to 9.17; p = 0.06) (Fig. 7). Owing to the inclusion of only two studies in this part of
An ideal treatment for OVCF should result in a lasting improvement in the symptoms and a durable correction of the kyphotic deformity. Currently, KP and VP are alternative treatments after the failure of medical therapy or if patients have intolerable pain. Although some studies18–20 have demonstrated that good clinical results and better quality of life can be achieved by KP or VP, it is unclear which of these two interventions provides the better outcome. The methodological quality assessment identified several limitations to the current evidence base. Ultimately, only one RCT and nine prospective comparative studies met the pre-defined eligibility criteria. All of the prospective comparative studies reported insufficient information on their randomization methods. Apart from two studies,10,11 all of the included studies, had poor concealment of allocation, allowing selection and allocation biases. Although the blinding of participants and surgeons was not performed in all studies, three studies10,11,16 described the assessor blinding method. The lack of blinding permitted further detection and performance biases, as well as the potential for type II statistical errors regarding the outcomes. In addition, clinical heterogeneity was induced, to a certain degree, by differing surgical technologies, the number of vertebral levels treated, fractures of different spinal vertebral bodies, and differing severities of the OVCF, as well as by the different indications of the surgeries in the included studies. The heterogeneity may have been caused by the greater risk of all types of biases because of the poor design of the non-randomized controlled trials. Accordingly, although the results of this meta-analysis should be deemed appropriate, these methodological quality defects should be considered when interpreting the findings.
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Fig. 4. Risk of bias. Each risk-of-bias item is demonstrated as percentages across all of the included studies in this meta-analysis of balloon kyphoplasty compared to percutaneous vertebroplasty for treating osteoporotic vertebral compression fractures. Table 1 Characteristics of studies included in the meta-analysis of balloon kyphoplasty compared to percutaneous vertebroplasty for treating osteoporotic vertebral compression fractures. Patient Age (years) numbers
Volume of No. of vertebral cement injected (cm3) bodies
Study
Country
Study design
VP
KP VP
20116 20107
Israel Canada
Prospective comparative study 31 14 Prospective comparative study 24 28
70.74 ± 13.4 75.57 ± 7.3 9/22 73 (52–89) 78 (57–94) 7/17
5/9 9/19
31 39
20108 201010 201015 20099 200911
Slovenia Taiwan Spain USA Germany
Prospective comparative study Randomized controlled trial Prospective comparative study Prospective comparative study Prospective comparative study
67.8 ± 5.4 72.3 ± 7.6 65.9 ± 1.9 68.9 ± 10.4 72.5 ± 5.7
10/36 11/39 9/21 17/73 8/22
5/22 51 12/38 50 5/25 42 53 6/24 30
Prospective comparative study 36 118 67.6 (53–95) 56/98 2009 Italy 200812 China Prospective comparative study 42 56 64 (31–74) 62 (28–73) 17/25 200513 Australia Prospective comparative study 28 23 70 (65–74) 7/21
47 21/35 42 5/18 35
KP VP
14
46 50 30 90 30
27 50 30 30
KP
Gender (M/F) VP
72.9 ± 5.6 74.3 ± 6.4 73 ± 1.5 73.8 ± 6.4
KP
14 56
KP
Follow-up (mo)
Lost to follow-up
VP
NR NR 12 1.8 (0.75–5.0) 3.2 (1.0–7.0) 42.3 42.2 32 5.5 ± 1.1 5.8 ± 1.7 12 50 5.56 ± 0.62 4.91 ± 0.65 6 69 NR NR 12 51 NR NR 12 30 4.9 ± 1.2 3.9 ± 1.5 13.5 13.7 152 3.2 2.5 33 56 NR NR 12 29 NR NR 24
NR for KP 6 for VP NR NR NR 10 for KP 11 for VP 10 NR NR
F = female, KP = kyphoplasty, M = male, mo = months, NR = not reported, SD = standard deviation, VP = vertebroplasty. Mean age was described as mean ± SD or mean (range). Volume of cement injected was described as mean ± SD or mean (range).
Fig. 5. Forest plot and tabulated data illustrating the mean difference (MD) in the visual analog scale (VAS) scores between the kyphoplasty (KP) and vertebroplasty (VP) procedures, showing that the two interventions arenot significantly different.
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Fig. 6. Forest plot and tabulated data illustrating the mean difference (MD) in Oswestry Disability Index (ODI) scores between the kyphoplasty (KP) and vertebroplasty (VP) procedures, showing that the two interventions are not significantly different.
Fig. 7. Forest plot and tabulated data illustrating the mean difference (MD) in operation time between the kyphoplasty (KP) and vertebroplasty (VP) procedures, showing that the two interventions are not significantly different.
Fig. 8. Forest plot and tabulated data illustrating the mean difference (MD) in postoperative kyphosis angle between the kyphoplasty (KP) and vertebroplasty (VP) procedures, showing that patients who underwent KP had a better kyphosis angle than patients who underwent VP in kyphosis angle postoperatively in the long term. However, the two interventions showed no significant difference in kyphosis angle postoperatively in the short term..
Regarding the short-term and long-term outcomes of the pooled VAS scores, no significant difference was found between the two procedures. The exact mechanism of pain reduction remains unclear. Belkoff et al.21,22 provided evidence of pain reduction attributable to the immobility and inhibition of micro movements of the fractured fragment. In addition, the cytotoxic effect of polymethylmethacrylate (PMMA) causes damage to terminal nerve endings and reduces pain.23 However, Togawa et al.24 reported that PMMA did not exert a definitive thermic
effect on pain reduction. Schofer et al.12 reported that significant pain reduction was achieved in each group suffering from fresh thoraco-lumbar compression fractures, whereas they found no difference in pain reduction between the two groups. For quality of life, KP seems to be more effective for short- and long-term functional improvement, but there was no significant difference in the ODI scores between the KP and VP groups, either for short- or long-term follow-up outcomes. Previous studies showed that quality of life is significantly improved by KP and
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Fig. 9. Forest plot and tabulated data illustrating the mean difference (MD) in postoperative anterior vertebral body height between the kyphoplasty (KP) and vertebroplasty (VP) procedures, showing that KP has a higher anterior vertebral body height and is therefore superior in this respect.
Fig. 10. Forest plot and tabulated data illustrating the risk ratio for cement leakage between the kyphoplasty (KP) and vertebroplasty (VP) procedures, showing that KP has a lower incidence of cement leakage and is therefore superior in this respect.
Fig. 11. Forest plot and tabulated data illustrating the risk ratio for adjacent-level fracture between the kyphoplasty (KP) and vertebroplasty (VP) procedures showing that there is no significant difference between the two interventions in this respect.
VP compared with preoperative status. The ODI scores may also be affected by the ongoing process of osteoporosis. In addition, the selection of patients may depend on different indications for KP or VP in non-randomized studies. Through KP, restoration and repositioning of the fractured vertebral body is achieved. Numerous publications show a significant postoperative increase in the anterior vertebral body height as a result of KP or VP compared with preoperative height. In our meta-analysis, we demonstrated a significant increase in the vertebral height in the KP group compared with the VP group. The restoration of the vertebral body height by VP was partially attributable to the patient’s position in the bed. By contrast, the restoration by KP can be traced back to the ability to restore the shape of the vertebral body via a balloon and to the patient’s position. However, Rollinghoff et al.10 and Schofer et al.12 demonstrated that there was no relationship between improvements in vertebral body height and clinical outcomes in the KP or VP group.
In our meta-analysis, the short-term postoperative kyphosis angle in the KP group was not significantly different from that in the VP group. However, the kyphosis angle at long-term follow-up was significantly superior for the KP group than for the VP group. Several factors might affect the measured kyphosis angles, however. First, the measurement of the short-term kyphosis angle may be affected by the patients’ pain and anxiety postoperatively. Second, the difference in the results may be attributable to the subsidence of the endplates of the index vertebrae. Third, the patients’ position in bed may affect the accuracy of the measurement. Overall, kyphosis angle measurements may be dependent on the different durations of follow-up. The reduction in angle depends more on the natural healing of the fracture than treatment.25 In addition, bias may make the outcomes unstable. Schofer et al.12 reported a reduction in the kyphosis angle by an average of 3–6° after KP, compared with a reduction of 1° after VP, and they suggested that the balloon-induced restoration had an additive effect.
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Regarding the incidence of adjacent-level fractures, there was no significant difference between KP and VP. Whether bone cement augmentation causes an increased incidence of new adjacent vertebral body fractures is a topic of ongoing discussion.26 Additionally, in patients with OVCF, it is difficult to discriminate between adjacent-level fractures following the operation and new OVCF. Hulme et al.,26 in a systematic review, showed that the incidence of adjacent-level fractures did not increase compared with that in an osteoporotic population that had already suffered a vertebral body fracture. Because of the small sample size, we cannot draw conclusions about complications. Moreover, because of insufficient blinding of assessment, the results might easily have been affected by subjective assessment. Apart from general complications, there are specific complications due to cement leakage. Severe complications occur in up to 8% of KP and VP cases.23 However, the most frequent complications, cement leakages, do not usually result in clinical symptoms. In this meta-analysis, the incidence of cement leakage after KP was lower than after VP. However, no cases of spinal stenosis or pulmonary embolism caused by cement leakage were reported in any of the included studies. To our knowledge, the low viscosity of cement and the high injection pressure during VP leads to more frequent leakage of cement through the fracture and the blood vessels than does KP. The filling of a cavity created by a balloon in the vertebral body with high-viscosity cement injected at low pressure is the methodological difference for KP, which leads to a lower rate of cement leakage. Lovi et al.15 reported that performing VP with stiffer cement decreases the risk of cement leakage. Our results are consistent with a previous systematic review that reported a cement leakage incidence of 9% after KP and 41% after VP.26 In addition to the causes of leakage, different ways of measuring cement leakage rates influence the results. Heini et al.23 showed that low rates of cement leakage have often been recorded by X-ray radiography, whereas high rates are found with computed tomography. Several other meta-analyses have been published on this topic. Taylor et al.27 reported that KP was more effective than conservative treatment for OVCF. Han et al.5 reviewed eight studies and reported that KP and VP had comparable outcomes for long-term VAS and ODI scores and had a similar risk for subsequent fractures and cement leakage. Our meta-analysis introduced two additional prospective comparative studies and found that a lower rate of cement leakage occurred in the KP group than in the VP group. One possible reason for the conflicting results in the two previously published meta-analyses is that these analyses included two non-randomized trials9,13 that introduced a higher risk of bias. When these two studies were removed from the pooled analysis, the results for cement leakage were not changed. The present meta-analysis reported the pooled value for radiological results, such as kyphosis correction or height restoration, which were not included in the previous meta-analyses. The limitations of this meta-analysis primarily include the following. The statistical power could be improved by including more studies. Owing to the finite number of studies included, a subgroup analysis was performed only on two defined overall follow-up times (short- or long-term), and this limitation may exert instability on the outcomes of the accurate time points. Poorly designed non-RCT are more likely to suffer from various kinds of bias.
5. Conclusion From this meta-analysis, the following conclusions can be drawn. First, in the treatment of OVCF, KP has a similar operation time and results with similar short-term postoperative kyphosis angles, pain relief and function scores to VP. Second, KP is superior
to VP for the restoration of the vertebral height of fractures and for improving the long-term kyphosis angle. Finally, KP has a significantly lower risk of cement leakage but a similar rate of adjacent-level fractures. Therefore, although KP and VP are both safe and effective procedures, KP is superior to VP for relieving the long-term kyphosis angle, improving the height of the vertebral body, and reducing the incidence of cement leakage. To confirm this assessment, high-quality RCT must be conducted. It will also be important to establish a guideline that preferentially indicates the use of KP or VP to obtain optimal clinical outcomes.
6. Conflicts of interest/disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication.
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D. Xing et al. / Journal of Clinical Neuroscience 20 (2013) 795–803 21. Belkoff SM, Mathis JM, Jasper LE, et al. The biomechanics of vertebroplasty. The effect of cement volume on mechanical behavior. Spine (Phila Pa 1976) 2001;26:1537–41. 22. Belkoff SM, Mathis JM, Jasper LE, et al. An ex vivo biomechanical evaluation of a hydroxyapatite cement for use with vertebroplasty. Spine (Phila Pa 1976) 2001;26:1542–6. 23. Heini PF, Walchli B, Berlemann U. Percutaneous transpedicular vertebroplasty with PMMA: operative technique and early results. A prospective study for the treatment of osteoporotic compression fractures. Eur Spine J 2000;9:445–50. 24. Togawa D, Bauer TW, Lieberman IH, et al. Histologic evaluation of human vertebral bodies after vertebral augmentation with polymethyl methacrylate. Spine (Phila Pa 1976) 2003;28:1521–7.
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25. Berlemann U, Franz T, Orler R, et al. Kyphoplasty for treatment of osteoporotic vertebral fractures: a prospective non-randomized study. Eur Spine J 2004;13:496–501. 26. Hulme PA, Krebs J, Ferguson SJ, et al. Vertebroplasty and kyphoplasty: a systematic review of 69 clinical studies. Spine (Phila Pa 1976) 2006;31:1983–2001. 27. Taylor RS, Fritzell P, Taylor RJ. Balloon kyphoplasty in the management of vertebral compression fractures: an updated systematic review and metaanalysis. Eur Spine J 2007;16:1085–100.
Contents lists available at SciVerse ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
A meta-analysis of balloon kyphoplasty compared to percutaneous vertebroplasty for treating osteoporotic vertebral compression fractures Dan Xing a,b, , Jian-Xiong Ma a, , Xin-Long Ma a,c,⇑, Jie Wang a, Wei-Guo Xu c, Yang Chen c, Dong-Hui Song b a
Department of Orthopaedics, Tianjin Medical University General Hospital, 154 Anshan Street, Heping District, Tianjin 300052, China Department of Orthopaedics, Tianjin Gongan Hospital, Heping District, Tianjin, China c Department of Orthopaedics Institute, Tianjin Hospital, Hexi District, Tianjin, China b
a r t i c l e
i n f o
Article history: Received 29 March 2012 Accepted 27 May 2012
Keywords: Kyphoplasty Meta-analysis Osteoporosis Vertebral compression fracture Vertebroplasty
a b s t r a c t A meta-analysis was conducted to assess the safety and efficacy of balloon kyphoplasty (KP) compared to percutaneous vertebroplasty (VP) in the treatment of osteoporotic vertebral compression fractures (OVCF). Ten studies, encompassing 783 patients, met the inclusion criteria. Overall, the results of the meta-analysis indicated that there were significant differences between the two groups in the long-term kyphosis angle (mean difference [MD] = –2.64, 95% confidence interval [CI] = –4.66 to –0.61; p = 0.01), the anterior height of the vertebral body (MD = 3.67, 95% CI = 1.40 to 5.94; p = 0.002), and the cement leakage rates (risk ratio [RR] = 0.70, 95% CI = 0.52 to 0.95; p = 0.02). However, there were no significant differences in the short-term visual analog scale (VAS) scores (MD = –0.57, 95% CI –1.33 to 0.20; p = 0.15), the longterm VAS scores (MD = –0.99, 95% CI = –2.29 to 0.31; p = 0.14), the short-term Oswestry Disability Index (ODI) scores (MD = –6.54, 95% CI = –14.57 to 1.48; p = 0.11), the long-term ODI scores (MD = –2.01, 95% CI = –11.75 to 7.73; p = 0.69), the operation time (MD = 4.47, 95% CI = –0.22 to 9.17; p = 0.06), the short-term kyphosis angle (MD = –2.25, 95% CI = –5.14 to 0.65; p = 0.13), or the adjacent-level fracture rates (RR = 1.52, 95% CI = 0.76 to 3.03; p = 0.24). This meta-analysis demonstrates that KP and VP are both safe and effective surgical procedures for treating OVCF. Compared with VP, KP can significantly relieve a long-term kyphosis angle, improve the height of the vertebral body, and reduce the incidence of bone cement leakage. However, because of the limitations of this meta-analysis, a large randomized controlled trial is required to confirm our findings. Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction Osteoporotic vertebral compression fractures (OVCF) are a significant health problem worldwide. These fractures result from a decrease in the anterior vertebral height and cause spinal deformity, reduced pulmonary function, restriction of the abdominal and thoracic contents, impaired mobility, and clinical depression. Conservative management cannot reverse the kyphotic deformity that causes the biomechanical changes in the spinal segment. Biomechanical changes may be one factor leading to an increased incidence of adjacent vertebral fractures. Vertebroplasty (VP) was introduced in 1984, and first described for the treatment of a hemangioma at the C2 vertebra. Since then, VP has been used for the treatment of vertebral compression fractures caused by myeloma, trauma, and osteoporosis. The new surgical technique, kyphoplasty (KP), was conceived and developed by ⇑ Corresponding author. Tel./fax: +86 22 60362062.
E-mail address: [email protected] (X.-L. Ma). These authors contributed equally to this work.
0967-5868/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jocn.2012.05.038
Dr Mark A. Reiley (Berkeley, CA, USA). Both of these surgical techniques not only increase bone strength but also alleviate the pain caused by OVCF. However, KP also seeks to restore the height of the vertebral body. Recently, two randomized controlled trials (RCT) indicated that each of these procedures achieves immediate pain relief unlike conservative treatments.1,2 Last year, Boonen et al.3 published the results of an RCT with a 24-month followup and reported that compared with non-surgical therapy, KP rapidly reduces pain and improves function, mobility, and quality of life, without increasing the risk of additional vertebral fractures. In a review article, Boonen et al.4 reported that VP and KP are generally safe procedures that provide faster pain relief and mobility recovery and, in some cases, vertebral height restoration than conservative management in the short-term. A previous meta-analysis recommended VP over KP for treating OVCF when considering the higher cost of the KP procedure.5 However, which of these two surgical procedures leads to better short-term and long-term outcomes remains controversial. Although few RCT have been conducted, several prospective comparative studies have been published. The purpose of this
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2. Materials and methods
fractures and bone cement leakage. In addition, we defined the short-term time point as no more than 1 week and the long-term time point as more than 6 months. If there were no reported data at those time points, when pooling data we used data from the time point closest to those times..
2.1. Search strategy
2.7. Assessment of methodological quality
To assemble all of the relevant literature, PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)compliant searches of MEDLINE, Embase, ScienceDirect, Ovid, and the Cochrane Central Register of Controlled Trials (CENTRAL) were performed on all peer-reviewed studies published until the end of May 2012 for RCT and prospective comparative studies comparing KP and VP in patients with OVCF. The following search terms were adopted for the database research: kyphoplasty, vertebral compression fracture, osteoporosis, and vertebroplasty. Secondary searches of unpublished literature were conducted by searching the World Health Organization’s International Clinical Trials Registry Platform, the UK National Research Register Archive, and Current Controlled Trials from their inception to March 1, 2012.
The risk of bias in the included studies was independently assessed by two authors (D.X. and X.-L.M.), in accordance with the Cochrane Handbook for Systematic Reviews of Interventions, version 5.0.6 A third author (J.W.) was the adjudicator when no consensus was achieved. We applied the ‘‘assessing the risk of bias’’ table, which includes the following key domains: adequate sequence generation, allocation of concealment, blinding, incomplete outcome data, freedom from selective reporting, and freedom from other biases.
meta-analysis is to evaluate the entire evidence base from RCT and prospective comparative studies to compare the efficacy and safety of KP and VP for patients with OVCF.
2.2. Inclusion criteria Studies were considered eligible for inclusion if they met the following criteria: study design, RCT or prospective comparative studies; population, patients with vertebral compression fractures of osteoporotic etiology; intervention, KP; and comparator, VP. In addition, the studies had to report at least one of the following outcomes: operation time, subjective pain perception, quality of life evaluation, adjacent vertebral fracture incidence, bone cement leakage, vertebral body height, and kyphosis angle post-operation. 2.3. Exclusion criteria Patients were excluded from the meta-analysis if they had a neoplastic etiology (i.e., metastasis or myeloma), an infection, neural compression, a traumatic fracture, a neurological deficit, or spinal stenosis. Other exclusion criteria were severe degenerative diseases of the spine, previous surgery at the involved vertebral body, and KP or VP with other invasive or semi-invasive intervention therapies.
2.8. Data synthesis and analysis We performed all meta-analyses with Review Manager software (RevMan Version 5.1; The Nordic Cochrane Center, The Cochrane Collaboration, Copenhagen, Denmark). For continuous outcomes, means and standard deviations were pooled to a mean difference (MD) and a 95% confidence interval (CI). For dichotomous outcomes, the risk ratio (RR) and the 95% CI were assessed. A probability of p < 0.05 was regarded as statistically significant. The assessment for statistical heterogeneity was calculated using the chi-square and I-square tests. The source of heterogeneity was investigated by a subgroup analysis and a sensitivity analysis. In this meta-analysis, the subgroup analysis was performed according to the short-term and long-term time points during the follow-up. The sensitivity analysis was performed by rejecting the study with the higher statistical heterogeneity. 3. Results 3.1. Search results
Two reviewers (D.X. and J.-X.M.) independently screened the title and abstract related to the eligibility criteria. Then, full-text intensive reading was performed when those studies might meet the inclusion criteria, and the literature was reviewed to determine the final inclusions. We resolved disagreements by discussion to reach a consensus.
A total of 231 titles and abstracts were reviewed, of which 10 studies7–16 eventually satisfied the eligibility criteria. One multicenter, prospective RCT that compared the short- and long-term safety and effectiveness of KP and VP in the treatment of OVCF has been completed but has not yet been published (ClinicalTrials.gov identifier, NCT00323609). Such trials that had recently been completed or were in recruitment but had no published data were excluded from the present study. Therefore, this study included one RCT11 and nine prospective comparative studies7–10,12–16 (Fig. 1). The funnel plot of the incidence of bone cement leakage demonstrated limited evidence of a small study exclusion and publication bias, given the asymmetric diagram with a few studies plotted on the left side of the funnel (Fig. 2).
2.5. Data extraction
3.2. Quality assessment
Two authors (D.X. and J.-X.M.) independently extracted the following data: study characteristics, types of interventions, numbers of vertebral bodies, surgical procedures, and outcome parameters. The extracted data were rechecked by X.-L.M.
Of the 10 included studies, only one study, the RCT,11 had a low risk of bias, and the other nine studies, the prospective comparative studies,7–10,12–16 had a high risk of bias. Only one trial11 reported an adequate generation of the allocation sequence, and two trials10,11 reported allocation concealment. Three studies10,11,16 reported a single-blinding to outcome assessors, and none reported double-blinding; seven others did not mention the blinding method. The methodological quality of the included studies is illustrated in Fig. 3. Judgments about each risk-of-bias item are presented as percentages across all of the included studies in Fig. 4.
2.4. Study selection
2.6. Outcomes The clinical outcomes included the visual analog scale (VAS), the Oswestry Disability Index (ODI), and the operation time. Radiographic outcomes included the kyphosis angle and the anterior vertebral body height. Complication outcomes were adjacent
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Fig. 1. Summary of the study selection and exclusion process.
One of the 10 studies7 included patients with a collapse P15% of the vertebral height and a VAS P5 but excluded those with a collapse P50% of the vertebral height and a local kyphotic deformity P30°. Movrin et al.9 recruited patients with a collapse 690% of the vertebral height. Two of the included studies10,12 only recruited patients with fresh OVCF of the A1 and A3 fracture types.17 Only Schofer et al.12 defined fresh fractures; they included fractures up to 28 days after the causative event. Only one study, the RCT,11 recruited patients with a thoraco-lumbar junction (T12–L1) OVCF. Santiago et al.16 recruited patients with none of the known causes of osteoporosis (such as corticosteroid therapy, inflammatory spondylo-arthropathy and diabetes mellitus). Patients in four of the included studies7,11–13 had only one vertebral fracture. The demographic characteristics of the included studies are summarized in Table 1. Fig. 2. Funnel plot to assess publication bias for the most frequently reported outcome: cement leakage rates. RR = risk ratio, SE = standard error. The asymmetrical funnel plot means publication bias could have existed in this meta-analysis of balloon kyphoplasty compared to percutaneous vertebroplasty for treating osteoporotic vertebral compression fractures.
3.3. Demographic characteristics One RCT and nine prospective comparative studies, consisting of 219 males and 564 females, were eligible for inclusion, with the individual sample size ranging from 45 to 154 patients. Three hundred and seventeen patients underwent KP, and 466 underwent VP. All of the included studies had defined eligibility criteria.
3.4. Outcomes analysis 3.4.1. Clinical outcomes The pain measured by the VAS was classified into short-term and long-term follow-up. We pooled the outcome values according to the subgroup analysis. Seven studies7–12,14 reported the VAS scores at short-term follow-up; there was no significant difference between KP and VP for heterogeneity (MD = –0.57, 95% CI = –1.33 to 0.20; p = 0.15). Long-term VAS scores were available for nine studies;8–16 the pooled results demonstrated no significant difference between KP and VP (MD = –0.99, 95% CI = –2.29 to 0.31; p = 0.14) (Fig. 5). In the five studies8,10,14–16 that provided ODI data, the subgroup analysis was performed according to short-term or long-term
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the meta-analysis, the subgroup and sensitivity analyses could not be performed. 3.4.2. Radiographic outcomes Six studies7,9–12 reported the kyphosis angle after operation. A subgroup analysis was performed, according to short-term and long-term follow-up. Three studies9,10,12 provided data on the short-term kyphosis angle after surgery. Our pooled results showed no significant differences between KP and VP (MD = –2.25, 95% CI = –5.14 to 0.65; p = 0.13). Four trials7,10–12 reported the longterm postoperative kyphosis angle. Patients who underwent KP had a better kyphosis angle than patients who underwent VP (MD = –2.64, 95% CI = –4.66 to –0.61; p = 0.01) (Fig. 8). The sensitivity analysis identified the trial reported by Rollinghoff et al.10 as contributing to the heterogeneity of the outcome. In the four studies10,11,13,16 that reported the postoperative anterior height of the vertebral body, there was a significant difference between the KP and VP groups (MD = 3.67, 95% CI = 1.40 to 5.94; p = 0.002) (Fig. 9). Therefore, patients who underwent KP had a better anterior height of the vertebral body than those who underwent VP. 3.4.3. Complication outcomes Nine studies7–10,12–16 reported complications related to cement leakage. The pooled analysis showed a significantly lower rate of bone cement leakage in the KP group (RR = 0.70, 95% CI = 0.52 to 0.95; p = 0.02) (Fig. 10). In the seven studies8–12,14,15 that provided information about adjacent vertebral compression fractures, there was no significant difference between the KP and VP groups (RR = 1.52, 95% CI = 0.76 to 3.03; p = 0.24) (Fig. 11).
4. Discussion
Fig. 3. Methodological quality of included studies showing the the risk-of-bias of each study in this meta-analysis of balloon kyphoplasty compared to percutaneous vertebroplasty for treating osteoporotic vertebral compression fractures.
follow-up. Two studies8,10 reported the short-term ODI scores. There was no significant difference between the KP and VP groups (MD = –6.54, 95% CI = –14.57 to 1.48; p = 0.11). For the five trials8,10,14–16 that provided long-term ODI data, there was also no significant difference between KP and VP (MD = –2.01, 95% CI –11.75 to 7.73; p = 0.69) (Fig. 6). Statistical evidence of heterogeneity was indicated, and the sensitivity analysis showed that the heterogeneity of outcomes could be attributed to the study reported by Kumar et al.8 The dates of the operation were available for two trials.11,13 The pooled results showed no significant difference between the KP and VP groups (MD = 4.47, 95% CI = –0.22 to 9.17; p = 0.06) (Fig. 7). Owing to the inclusion of only two studies in this part of
An ideal treatment for OVCF should result in a lasting improvement in the symptoms and a durable correction of the kyphotic deformity. Currently, KP and VP are alternative treatments after the failure of medical therapy or if patients have intolerable pain. Although some studies18–20 have demonstrated that good clinical results and better quality of life can be achieved by KP or VP, it is unclear which of these two interventions provides the better outcome. The methodological quality assessment identified several limitations to the current evidence base. Ultimately, only one RCT and nine prospective comparative studies met the pre-defined eligibility criteria. All of the prospective comparative studies reported insufficient information on their randomization methods. Apart from two studies,10,11 all of the included studies, had poor concealment of allocation, allowing selection and allocation biases. Although the blinding of participants and surgeons was not performed in all studies, three studies10,11,16 described the assessor blinding method. The lack of blinding permitted further detection and performance biases, as well as the potential for type II statistical errors regarding the outcomes. In addition, clinical heterogeneity was induced, to a certain degree, by differing surgical technologies, the number of vertebral levels treated, fractures of different spinal vertebral bodies, and differing severities of the OVCF, as well as by the different indications of the surgeries in the included studies. The heterogeneity may have been caused by the greater risk of all types of biases because of the poor design of the non-randomized controlled trials. Accordingly, although the results of this meta-analysis should be deemed appropriate, these methodological quality defects should be considered when interpreting the findings.
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Fig. 4. Risk of bias. Each risk-of-bias item is demonstrated as percentages across all of the included studies in this meta-analysis of balloon kyphoplasty compared to percutaneous vertebroplasty for treating osteoporotic vertebral compression fractures. Table 1 Characteristics of studies included in the meta-analysis of balloon kyphoplasty compared to percutaneous vertebroplasty for treating osteoporotic vertebral compression fractures. Patient Age (years) numbers
Volume of No. of vertebral cement injected (cm3) bodies
Study
Country
Study design
VP
KP VP
20116 20107
Israel Canada
Prospective comparative study 31 14 Prospective comparative study 24 28
70.74 ± 13.4 75.57 ± 7.3 9/22 73 (52–89) 78 (57–94) 7/17
5/9 9/19
31 39
20108 201010 201015 20099 200911
Slovenia Taiwan Spain USA Germany
Prospective comparative study Randomized controlled trial Prospective comparative study Prospective comparative study Prospective comparative study
67.8 ± 5.4 72.3 ± 7.6 65.9 ± 1.9 68.9 ± 10.4 72.5 ± 5.7
10/36 11/39 9/21 17/73 8/22
5/22 51 12/38 50 5/25 42 53 6/24 30
Prospective comparative study 36 118 67.6 (53–95) 56/98 2009 Italy 200812 China Prospective comparative study 42 56 64 (31–74) 62 (28–73) 17/25 200513 Australia Prospective comparative study 28 23 70 (65–74) 7/21
47 21/35 42 5/18 35
KP VP
14
46 50 30 90 30
27 50 30 30
KP
Gender (M/F) VP
72.9 ± 5.6 74.3 ± 6.4 73 ± 1.5 73.8 ± 6.4
KP
14 56
KP
Follow-up (mo)
Lost to follow-up
VP
NR NR 12 1.8 (0.75–5.0) 3.2 (1.0–7.0) 42.3 42.2 32 5.5 ± 1.1 5.8 ± 1.7 12 50 5.56 ± 0.62 4.91 ± 0.65 6 69 NR NR 12 51 NR NR 12 30 4.9 ± 1.2 3.9 ± 1.5 13.5 13.7 152 3.2 2.5 33 56 NR NR 12 29 NR NR 24
NR for KP 6 for VP NR NR NR 10 for KP 11 for VP 10 NR NR
F = female, KP = kyphoplasty, M = male, mo = months, NR = not reported, SD = standard deviation, VP = vertebroplasty. Mean age was described as mean ± SD or mean (range). Volume of cement injected was described as mean ± SD or mean (range).
Fig. 5. Forest plot and tabulated data illustrating the mean difference (MD) in the visual analog scale (VAS) scores between the kyphoplasty (KP) and vertebroplasty (VP) procedures, showing that the two interventions arenot significantly different.
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Fig. 6. Forest plot and tabulated data illustrating the mean difference (MD) in Oswestry Disability Index (ODI) scores between the kyphoplasty (KP) and vertebroplasty (VP) procedures, showing that the two interventions are not significantly different.
Fig. 7. Forest plot and tabulated data illustrating the mean difference (MD) in operation time between the kyphoplasty (KP) and vertebroplasty (VP) procedures, showing that the two interventions are not significantly different.
Fig. 8. Forest plot and tabulated data illustrating the mean difference (MD) in postoperative kyphosis angle between the kyphoplasty (KP) and vertebroplasty (VP) procedures, showing that patients who underwent KP had a better kyphosis angle than patients who underwent VP in kyphosis angle postoperatively in the long term. However, the two interventions showed no significant difference in kyphosis angle postoperatively in the short term..
Regarding the short-term and long-term outcomes of the pooled VAS scores, no significant difference was found between the two procedures. The exact mechanism of pain reduction remains unclear. Belkoff et al.21,22 provided evidence of pain reduction attributable to the immobility and inhibition of micro movements of the fractured fragment. In addition, the cytotoxic effect of polymethylmethacrylate (PMMA) causes damage to terminal nerve endings and reduces pain.23 However, Togawa et al.24 reported that PMMA did not exert a definitive thermic
effect on pain reduction. Schofer et al.12 reported that significant pain reduction was achieved in each group suffering from fresh thoraco-lumbar compression fractures, whereas they found no difference in pain reduction between the two groups. For quality of life, KP seems to be more effective for short- and long-term functional improvement, but there was no significant difference in the ODI scores between the KP and VP groups, either for short- or long-term follow-up outcomes. Previous studies showed that quality of life is significantly improved by KP and
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Fig. 9. Forest plot and tabulated data illustrating the mean difference (MD) in postoperative anterior vertebral body height between the kyphoplasty (KP) and vertebroplasty (VP) procedures, showing that KP has a higher anterior vertebral body height and is therefore superior in this respect.
Fig. 10. Forest plot and tabulated data illustrating the risk ratio for cement leakage between the kyphoplasty (KP) and vertebroplasty (VP) procedures, showing that KP has a lower incidence of cement leakage and is therefore superior in this respect.
Fig. 11. Forest plot and tabulated data illustrating the risk ratio for adjacent-level fracture between the kyphoplasty (KP) and vertebroplasty (VP) procedures showing that there is no significant difference between the two interventions in this respect.
VP compared with preoperative status. The ODI scores may also be affected by the ongoing process of osteoporosis. In addition, the selection of patients may depend on different indications for KP or VP in non-randomized studies. Through KP, restoration and repositioning of the fractured vertebral body is achieved. Numerous publications show a significant postoperative increase in the anterior vertebral body height as a result of KP or VP compared with preoperative height. In our meta-analysis, we demonstrated a significant increase in the vertebral height in the KP group compared with the VP group. The restoration of the vertebral body height by VP was partially attributable to the patient’s position in the bed. By contrast, the restoration by KP can be traced back to the ability to restore the shape of the vertebral body via a balloon and to the patient’s position. However, Rollinghoff et al.10 and Schofer et al.12 demonstrated that there was no relationship between improvements in vertebral body height and clinical outcomes in the KP or VP group.
In our meta-analysis, the short-term postoperative kyphosis angle in the KP group was not significantly different from that in the VP group. However, the kyphosis angle at long-term follow-up was significantly superior for the KP group than for the VP group. Several factors might affect the measured kyphosis angles, however. First, the measurement of the short-term kyphosis angle may be affected by the patients’ pain and anxiety postoperatively. Second, the difference in the results may be attributable to the subsidence of the endplates of the index vertebrae. Third, the patients’ position in bed may affect the accuracy of the measurement. Overall, kyphosis angle measurements may be dependent on the different durations of follow-up. The reduction in angle depends more on the natural healing of the fracture than treatment.25 In addition, bias may make the outcomes unstable. Schofer et al.12 reported a reduction in the kyphosis angle by an average of 3–6° after KP, compared with a reduction of 1° after VP, and they suggested that the balloon-induced restoration had an additive effect.
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Regarding the incidence of adjacent-level fractures, there was no significant difference between KP and VP. Whether bone cement augmentation causes an increased incidence of new adjacent vertebral body fractures is a topic of ongoing discussion.26 Additionally, in patients with OVCF, it is difficult to discriminate between adjacent-level fractures following the operation and new OVCF. Hulme et al.,26 in a systematic review, showed that the incidence of adjacent-level fractures did not increase compared with that in an osteoporotic population that had already suffered a vertebral body fracture. Because of the small sample size, we cannot draw conclusions about complications. Moreover, because of insufficient blinding of assessment, the results might easily have been affected by subjective assessment. Apart from general complications, there are specific complications due to cement leakage. Severe complications occur in up to 8% of KP and VP cases.23 However, the most frequent complications, cement leakages, do not usually result in clinical symptoms. In this meta-analysis, the incidence of cement leakage after KP was lower than after VP. However, no cases of spinal stenosis or pulmonary embolism caused by cement leakage were reported in any of the included studies. To our knowledge, the low viscosity of cement and the high injection pressure during VP leads to more frequent leakage of cement through the fracture and the blood vessels than does KP. The filling of a cavity created by a balloon in the vertebral body with high-viscosity cement injected at low pressure is the methodological difference for KP, which leads to a lower rate of cement leakage. Lovi et al.15 reported that performing VP with stiffer cement decreases the risk of cement leakage. Our results are consistent with a previous systematic review that reported a cement leakage incidence of 9% after KP and 41% after VP.26 In addition to the causes of leakage, different ways of measuring cement leakage rates influence the results. Heini et al.23 showed that low rates of cement leakage have often been recorded by X-ray radiography, whereas high rates are found with computed tomography. Several other meta-analyses have been published on this topic. Taylor et al.27 reported that KP was more effective than conservative treatment for OVCF. Han et al.5 reviewed eight studies and reported that KP and VP had comparable outcomes for long-term VAS and ODI scores and had a similar risk for subsequent fractures and cement leakage. Our meta-analysis introduced two additional prospective comparative studies and found that a lower rate of cement leakage occurred in the KP group than in the VP group. One possible reason for the conflicting results in the two previously published meta-analyses is that these analyses included two non-randomized trials9,13 that introduced a higher risk of bias. When these two studies were removed from the pooled analysis, the results for cement leakage were not changed. The present meta-analysis reported the pooled value for radiological results, such as kyphosis correction or height restoration, which were not included in the previous meta-analyses. The limitations of this meta-analysis primarily include the following. The statistical power could be improved by including more studies. Owing to the finite number of studies included, a subgroup analysis was performed only on two defined overall follow-up times (short- or long-term), and this limitation may exert instability on the outcomes of the accurate time points. Poorly designed non-RCT are more likely to suffer from various kinds of bias.
5. Conclusion From this meta-analysis, the following conclusions can be drawn. First, in the treatment of OVCF, KP has a similar operation time and results with similar short-term postoperative kyphosis angles, pain relief and function scores to VP. Second, KP is superior
to VP for the restoration of the vertebral height of fractures and for improving the long-term kyphosis angle. Finally, KP has a significantly lower risk of cement leakage but a similar rate of adjacent-level fractures. Therefore, although KP and VP are both safe and effective procedures, KP is superior to VP for relieving the long-term kyphosis angle, improving the height of the vertebral body, and reducing the incidence of cement leakage. To confirm this assessment, high-quality RCT must be conducted. It will also be important to establish a guideline that preferentially indicates the use of KP or VP to obtain optimal clinical outcomes.
6. Conflicts of interest/disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication.
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