International Journal of Surgery 12 (2014) 1249e1253
Contents lists available at ScienceDirect
International Journal of Surgery journal homepage: www.journal-surgery.net
Original research
The clinical efficacy of vertebroplasty on osteoporotic vertebral compression fracture: A meta-analysis Jing Tian a, Liangbi Xiang b, Dapeng Zhou b, Qingyu Fan a, Baoan Ma a, * a b
Department of Orthopedics, Tangdu Hospital of the Fourth Military Medical University, Xi'an 710038, Shannxi 710038, China Department of Orthopedics, General Hospital of Shenyang Military Area Command, Shenyang 110840, China
h i g h l i g h t s Efficacy of vertebroplasty on osteoporotic vertebral compression fracture (VCF) was accessed. Vertebroplasty had significant efficacy on pain relief in osteoporotic VCF. Vertebroplasty had similar adjacent vertebral fracture incidence with traditional treatment.
a r t i c l e i n f o
a b s t r a c t
Article history: Received 3 January 2014 Received in revised form 12 September 2014 Accepted 25 October 2014 Available online 28 October 2014
We investigated the clinical efficacy of vertebroplasty (VP) for the treatment of osteoporotic vertebral compression fracture (OVCF). We searched the online databases such as MEDLINE, EMBASE, EBSCO, Springer, Ovid and Cochrane library citations up to May 2012 and 5 eligible studies were included in this study. The meta-analysis was conducted using software RevMan 5.0. For the continuous data, the weighted mean difference (WMD) and its 95% confidence interval (CI) were calculated and the odds ratio (OR) and the corresponding 95% CI were calculated for the dichotomous data. The results demonstrated that the Visual Analogue Scale (VAS) score of patients treated with VP was significantly lower than that treated with traditional treatment at each time point (one week: WMD ¼ 2.55, 95% CI, 3.08 to 2.02, P < 0.0001; 12 weeks: WMD ¼ 0.90, 95% CI, 1.22 to 0.57, P < 0.0001; 24 weeks: WMD ¼ 1.75, 95% CI, 2.30 to 1.19, P < 0.0001; 48 weeks: WMD ¼ 1.75, 95% CI, 2.30 to 1.19, P < 0.001). For The incidence of adjacent vertebral fracture, the overall estimate (OR ¼ 2.06, 95% CI: 0.26 to 16.29, P ¼ 0.50) indicated that there was no statistically significant difference between VP and traditional treatment. In conclusion, the OVCF patients treated by VP had statistically significant improvements in pain relief compared with the traditional treatment and there was the similar incidence of adjacent vertebral fracture between the patients treated by VP and traditional treatment. © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
Keywords: Vertebroplasty Osteoporosis Vertebral compression fracture System assessment
1. Introduction Osteoporosis (porous bones) as a systemic skeletal disease, is characterized by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase of bone fragility and susceptibility to fractures [1]. Vertebral compression fracture (VCF) is the most common complication of osteoporosis [2]. The risk of VCF was increased with age [3]. Osteoporotic VCF (OVCF) is a leading cause of disability and morbidity in the elderly [4]. As the most common fractures in the elders with osteoporosis, it was
* Corresponding author. Department of Orthopedics, Tangdu Hospital of the Fourth Military Medical University, No.1 Xin'si Road, Xi'an 710038, Shannxi Province, China. E-mail address: [email protected] (B. Ma). http://dx.doi.org/10.1016/j.ijsu.2014.10.027 1743-9191/© 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
occurred in 20% of people older than 70 years and in 16% of postmenopausal women [5]. It was reported that there were more than 700,000 osteoporotic VCFs per year in the United States and approximately 85% of these fractures were due to primary osteoporosis [6]. Traditional treatments for the patients with OVCF include bed rest, oral or parenteral analgesics, muscle relaxants, external back bracing, and physical therapy [7]. Because the narcotic agents and a variety of expensive spinal orthoses are commonly used in the traditional treatment [8], the effectiveness of them may be limited due to the high cost and the long-time treatment. Thus, finding a treatment with high efficacy and low cost is a major task in clinical study for OVCF. Vertebroplasty (VP) is a minimally invasive technique in vertebral body lesion therapy. It was reported that VP could effectively
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treat pain and immobility which caused by VCF [9e12]. Although the efficacy and safety of VP is affirmed constantly [13e15], the disputes on the efficacy and complications of VP are still existed in recent studies. The study of Ploeg et al. reported that there were insufficient evidence to reliably assess efficacy of VP [16], while Blasco J et al. reported that VP achieved faster pain relief but was associated with a higher incidence in vertebral fractures. Therefore, we conducted a meta-analysis to statistically analyze the data from the recent studies in order to provide more reliable basis for the clinical efficacy of VP in treating OVCF. 2. Materials and methods 2.1. Search criteria and strategies We retrieved the databases such as MEDLINE, EMBASE, EBSCO, Springer, Ovid and Cochrane library up to May 2012. The keywords included “vertebroplasty”, “osteoporosis” and “vertebral compression fracture”. The studies should meet the following inclusion criteria: (1) researches were clinical randomized controlled trials (RCTs) related to VP in the treatment of OVCF; (2) studies were published abroad; (3) the patients in experimental group should be treated with VP and the patients in the control group were treated by the traditional treatment including bed rest, oral antiosteoporotic drugs and painkillers, wearing the spinal orthosis, reset, or functional exercise; (4) the Visual Analogue Scale (VAS) score for pain or/and complications were investigated. The studies were excluded if (1) the patients in the studies suffered cardiopulmonary dysfunction and other serious diseases, (2) there was no specific data except the curves of the indicators, (3) the patients were not confirmed by diagnosis and (4) the studies were nonRCTs. 2.2. Quality assessment and data extraction Two investigators independently assessed the study quality and extracted the data. Disagreements were resolved by discussion. The study quality was evaluated based on the random allocation method, blind method and evaluation of withdrawal. The extracted data included general information (first author, year and region) and study characteristics (design, follow-up time, sample size, age and gender of subjects and the data of outcomes). 2.3. Statistical analysis The meta-analysis was conducted using the Cochrane software RevMan 5.0. For continuous data, the weighted mean difference (WMD) and its 95% confidence interval (CI) were calculated. For dichotomous data, the odds ratio (OR) and the corresponding 95% CI were calculated. The Z-test was used for assessing the significance of the pooled OR and WMD, with P < 0.05 considered statistically significant. Heterogeneity among the included studies was evaluated by chi-square test and I2 statistic. If no significantly heterogeneity (P > 0.05 or I2 < 50%) was found, the effect size was pooled based on the fixed-effects model. Otherwise, randomeffects model was used.
one non-RCT and four literature which did not report the treatment of OVCF with VP were excluded. As a result, 5 literature were identified (Fig. 1). 3.2. Characteristics of included studies According to the inclusion and exclusion criteria, a total of five eligible studies [17e21] were included in this meta-analysis. The published year was ranged from 2007 to 2012. All the included subjects were elders aged over 50 years old. The duration of followup in these studies was ranged from 2 weeks to 36 months. All the included studies were RCTs. Among them, the study of Farrokhi et al. [18] was a single-blind RCT and the study of Rousing et al. [20] was a double-blind RCT. The other three studies did not define the blind method (Table 1). 3.3. Statistical analysis 3.3.1. Comparison of VAS score Two included studies [18,19] investigated the VAS score at one week after treatment. Fixed effects model was used because no significant heterogeneity was found (P ¼ 0.06, I2 ¼ 71%). The pooled estimate (WMD ¼ 2.55, 95% CI: 3.08 to 2.02, P < 0.00001) showed that there was statistically significant difference between the experimental and control group. The result indicated that the VAS score of the patients in VP group were significantly lower than that in control group at one week after treatment (Fig. 2A). The VAS score at 12 weeks after treatment was shown in two included studies [19,20]. There was no significant heterogeneity among the studies (P ¼ 0.18, I2 ¼ 44%), so fixed effects model was used. The pooled WMD (0.90, 95% CI: 1.22 to 0.57, P < 0.00001) showed that the statistically significant difference was existed between the two groups. It suggested that the VAS score of patients in VP group was significantly lower than that in control group at 12 weeks after treatment (Fig. 2B). Two included studies [18,19] involved in VAS score at 24 weeks after treatment. Fixed effects model was used for no significant heterogeneity between the studies (P ¼ 0.59, I2 ¼ 0%). The overall WMD was 1.75 (95% CI: 2.30 to 1.19, P < 0.00001), which showed the statistically significant difference between the two groups. It indicated that the VAS score of the patients in VP group was significantly lower compared with that in control group at 24 weeks after treatment (Fig. 2C). A total of three studies [18e20] showed the VAS score at 48 weeks after treatment. Fixed effects model was used for no significant heterogeneity among the studies (P ¼ 0.06, I2 ¼ 65%). The pooled estimate (WMD ¼ 1.12, 95% CI: 1.43 to 0.81, P < 0.00001) showed a statistically significant difference between
3. Results 3.1. Literature search After the initial search in the databases, a total of 1073 potentially relevant literature were identified. Then 12 articles were remained by omitting the duplicated and obviously irrelevant literature. Based on exclusion and inclusion criteria, two reviewers,
Fig. 1. The flow diagram of literature screening.
J. Tian et al. / International Journal of Surgery 12 (2014) 1249e1253
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Table 1 The characteristics of the included studies. First author
year
Region
Sample size Experiment/control
Age Experiment/control
Female (%) Experiment/control
Design
Duration of follow-up
Indicators
Blasco
2012
Europe
64/61
73/82
RCT
12 months
Farrokhi
2011
Asia
40/42
71.33 ± 9.95/ 75.27 ± 8.53 72 (59e90)/ 74 (55e87)
30/30
Single-blind RCT
36 months
Klazen
2010
Europe
75.2 ± 9$8/ 75.4 ± 8$4
69/69
RCT
12 months
Rousing
2009
Europe
97/93a 92/86b 89/81c 86/77d 23/23e 22/22f 23/22g
Adjacent vertebral fracture incidence VAS score at 1, 24 and 48 weeks after treatment, adjacent vertebral fracture incidence VAS score at 1, 12, 24 and 48 weeks after treatment
80 (65e96)/ 80 (71e93)
NA
Double-blind RCT
3 months
Voormolen
2007
Europe
18/16
72 (59e84)/ 74 (55e88)
14/14
RCT
Two weeks
VAS score at 12 and 48 weeks after treatment, adjacent vertebral fracture incidence Adjacent vertebral fracture incidence
NA: not provided; VAS: visual analogue scale; RCT: randomized controlled trial. a Sample size of Klazen et al. in the indicator of VAS score at 1 week after treatment. b Sample size of Klazen et al. in the indicator of VAS score at 12 week after treatment. c Sample size of Klazen et al. in the indicator of VAS score at 24 week after treatment. d Sample size of Klazen et al. in the indicator of VAS score at 48 week after treatment. e Sample size of Rousing et al. in the indicator of VAS score at 12 week after treatment. f Sample size of Rousing et al. in the indicator of VAS score at 48 week after treatment. g Sample size of Rousing et al. in the indicator of adjacent vertebral fracture incidence.
Fig. 2. Forest plots of VAS score after treatment. A: VAS score at one week after treatment; B: VAS score at 12 weeks after treatment; C: VAS score at 24 weeks after treatment; D: VAS score at 24 weeks after treatment.
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Fig. 3. Forest plots of the adjacent vertebral fracture incidence.
the experimental and control group. It suggested that the VAS score of the patients in VP group was significantly lower than that in control group at 48 weeks after treatment (Fig. 2D). 3.3.2. Comparison of complications Four included studies [17,18,20,21] reported the incidence of adjacent vertebral fracture after treatment. Significant heterogeneity (P ¼ 0.03; I2 ¼ 67%) was found among the studies, so random effects model was used. The overall estimate (OR ¼ 2.06, 95% CI: 0.26 to 16.29, P ¼ 0.50) indicated that there was no statistically significant difference between the two groups for the adjacent vertebral fracture incidence (Fig. 3). In addition, Farrokhi MR et al. observed that epidural cement leakage caused severe right lower-extremity pain and weakness in one patient [18]. Meanwhile, no other serious complications or adverse events were reported in all the included studies.
sample size was small. The result of this study may be questioned and more studies with large sample size were required to verify these result. Second, the publication bias was not assessed because of small number of included studies for each indicator. Third, random method of some trials was undefined. The results of this study may be affected by the different study designs of the included studies. Moreover, the sources of heterogeneity need to be explored in the further studies. 5. Conclusion Based on the result in this study, we concluded that the OVCF patients treated by VP had statistically significant improvements in pain relief and similar incidence of adjacent vertebral fracture compared with the traditional treatment. Ethical approval
4. Discussion Low back pain is the main symptom of OVCF, and long-term pain will seriously influence the life quality of the OVCF patients [22]. The causes of pain in OVCF patients are complicated, which may related to nerve endings irritated by slight movement of vertebral fracture [23e25]. In this study, the results showed that the VAS score of patients in VP group was significantly lower than that in traditional treatment group at each time point. It suggested the OVCF patients treated by VP had statistically significant improvements in pain relief. It was consistent with the result of other published studies [11,26,27]. The mechanism of VP in treating OVCF patients may be associated with the characteristics of VP and the causes of pain in OVCF patients. We speculated that, firstly, the curing material (usually polymethyl methacrylate) can fix the micro fractures, strengthen the vertebral body and relieve nerve irritation, then large amounts of heat is released with the concretion and agglomeration of polymethyl methacrylate and the temperature is increased [28,29]. The increase of temperature ascension, extrusion of the solid and chemical toxicity of the polymethyl methacrylate may lead to the necrosis of nerve endings, so as to relieve pain [30,31]. In addition, the present study showed no difference was found in the incidence of adjacent vertebral fracture between VP and traditional treatment group. Meanwhile, severe right lowerextremity pain and weakness caused by the leakage of cement was observed by Farrokhi MR et al. [18]. It has been reported that leakage of cement outside the vertebral body was markedly common in VP [16]. Although no other serious complications or adverse events were reported in all the included studies in this metaanalysis, some potentially rare complications such as pulmonary embolism caused by the leakage of cement can be devastating [32]. Therefore, more studies must be done to investigate the low incidence but high devastating complications. Some limitations of this meta-analysis should be mentioned. First, for each indicator, the number of the included studies and
None. Financial support None. Author contribution Study conception and design: Baoan Ma, Qingyu Fan. Acquisition of data: Jing Tian. Analysis and interpretation of data: Liangbi Xiang. Drafting the manuscript: Dapeng Zhou, Jing Tian, Critical revision of manuscript: Baoan Ma. Conflict of interest None. Acknowledgment This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. References [1] O. Johnell, J. Kanis, Epidemiology of osteoporotic fractures, Osteoporos. Int. 16 (2005) S3eS7. [2] F.M. Phillips, E. Ho, M. Campbell-Hupp, T. Mcnally, F.T. Wetzel, P. Gupta, Early radiographic and clinical results of balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures, Spine 28 (2003) 2260e2265. [3] J.L. Old, M. Calvert, Vertebral compression fractures in the elderly, Am. Fam. Physician (2004) 69. [4] F.M. Phillips, Minimally invasive treatments of osteoporotic vertebral compression fractures, Spine 28 (2003) S45eS53. [5] L. Cohen, Fractures of the osteoporotic spine, Orthop. Clin. North Am. 21 (1990) 143e150. [6] B.L. Riggs, L. Melton Iii, The worldwide problem of osteoporosis: insights afforded by epidemiology, Bone 17 (1995) S505eS511.
J. Tian et al. / International Journal of Surgery 12 (2014) 1249e1253 [7] I. Lieberman, S. Dudeney, M.-K. Reinhardt, G. Bell, Initial outcome and efficacy of “kyphoplasty” in the treatment of painful osteoporotic vertebral compression fractures, Spine 26 (2001) 1631e1637. [8] K.S. Ryu, C.K. Park, M.C. Kim, J.K. Kang, Dose-dependent epidural leakage of polymethylmethacrylate after percutaneous vertebroplasty in patients with osteoporotic vertebral compression fractures, J. Neurosurg. Spine 96 (2002) 56e61. [9] M.E. Jensen, A.J. Evans, J.M. Mathis, D.F. Kallmes, H.J. Cloft, J.E. Dion, Percutaneous polymethylmethacrylate vertebroplasty in the treatment of osteoporotic vertebral body compression fractures: technical aspects, AJNR Am. J. Neuroradiol. 18 (1997) 1897e1904. [10] A. Hadjipavlou, M. Tzermiadianos, P. Katonis, M. Szpalski, Percutaneous vertebroplasty and balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures and osteolytic tumours, J. Bone Jt. Surg. Br. 87 (2005) 1595e1604. [11] R. Buchbinder, R.H. Osborne, P.R. Ebeling, et al., A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures, N. Engl. J. Med. 361 (2009) 557e568. [12] R.S. Taylor, R.J. Taylor, P. Fritzell, Balloon kyphoplasty and vertebroplasty for vertebral compression fractures: a comparative systematic review of efficacy and safety, Spine 31 (2006) 2747e2755. [13] K. Kobayashi, K. Shimoyama, K. Nakamura, K. Murata, Percutaneous vertebroplasty immediately relieves pain of osteoporotic vertebral compression fractures and prevents prolonged immobilization of patients, Eur. Radiol. 15 (2005) 360e367. [14] D.F. Kallmes, B.A. Comstock, P.J. Heagerty, et al., A randomized trial of vertebroplasty for osteoporotic spinal fractures, N. Engl. J. Med. 361 (2009) 569e579. [15] J.C. Eck, D. Nachtigall, S.C. Humphreys, S.D. Hodges, Comparison of vertebroplasty and balloon kyphoplasty for treatment of vertebral compression fractures: a meta-analysis of the literature, Spine J. 8 (2008) 488e497. [16] W.T. Ploeg, A.G. Veldhuizen, M.S. Sietsma, Percutaneous vertebroplasty as a treatment for osteoporotic vertebral compression fractures: a systematic review, Eur. Spine J. 15 (2006) 1749e1758. [17] J. Blasco, A. Martinez-Ferrer, J. Macho, et al., Effect of vertebroplasty on pain relief, quality of life, and the incidence of new vertebral fractures: a 12-month randomized follow-up, controlled trial, J. Bone Min. Res. 27 (2012) 1159e1166. [18] M.R. Farrokhi, E. Alibai, Z. Maghami, Randomized controlled trial of percutaneous vertebroplasty versus optimal medical management for the relief of pain and disability in acute osteoporotic vertebral compression fractures: clinical article, J. Neurosurg. Spine 14 (2011) 561e569.
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[19] C.A. Klazen, P.N. Lohle, J. De Vries, et al., Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomised trial, Lancet 376 (2010) 1085e1092. [20] R. Rousing, M.O. Andersen, S.M. Jespersen, K. Thomsen, J. Lauritsen, Percutaneous vertebroplasty compared to conservative treatment in patients with painful acute or subacute osteoporotic vertebral fractures: three-months follow-up in a clinical randomized study, Spine 34 (2009) 1349e1354. [21] M. Voormolen, W. Mali, P. Lohle, et al., Percutaneous vertebroplasty compared with optimal pain medication treatment: short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures. The VERTOS study, AJNR Am. J. Neuroradiol. 28 (2007) 555e560. [22] S.R. Garfin, R.A. Buckley, J. Ledlie, Balloon kyphoplasty for symptomatic vertebral body compression fractures results in rapid, significant, and sustained improvements in back pain, function, and quality of life for elderly patients, Spine 31 (2006) 2213e2220. [23] J.D. Barr, M.S. Barr, T.J. Lemley, R.M. Mccann, Percutaneous vertebroplasty for pain relief and spinal stabilization, Spine 25 (2000) 923e928. [24] P.J. Siddall, M.J. Cousins, Spinal pain mechanisms, Spine 22 (1997) 98e104. [25] H. Yoshizawa, J.P. O'brien, W. Thomas Smith, M. Trumper, The neuropathology of intervertebral discs removed for low-back pain, J. Pathol. 132 (1980) 95e104. [26] N. Watts, S. Harris, H. Genant, Treatment of painful osteoporotic vertebral fractures with percutaneous vertebroplasty or kyphoplasty, Osteoporos. Int. 12 (2001) 429e437. [27] R. Buchbinder, R.H. Osborne, P.R. Ebeling, et al., Efficacy and safety of vertebroplasty for treatment of painful osteoporotic vertebral fractures: a randomised controlled trial [ACTRN012605000079640], BMC Musculoskelet. Disord. 9 (2008) 156. [28] J.J. Verlaan, F.C. Oner, A.J. Verbout, W.J. Dhert, Temperature elevation after vertebroplasty with polymethyl-methacrylate in the goat spine, J. Biomed. Mater. Res. A 67 (2003) 581e585. [29] K.-Y. Chen, H.-I. Ma, Y.-H. Chiang, Percutaneous transpedicular vertebroplasty with polymethyl methacrylate for pathological fracture of the spine, J. Clin. Neurosci. 16 (2009) 1300e1304. [30] H. Deramond, N. Wright, S. Belkoff, Temperature elevation caused by bone cement polymerization during vertebroplasty, Bone 25 (1999) 17Se21S. [31] K. Hochmuth, D. Proschek, W. Schwarz, M. Mack, A. Kurth, T. Vogl, Percutaneous vertebroplasty in the therapy of osteoporotic vertebral compression fractures: a critical review, Eur. Radiol. 16 (2006) 998e1004. [32] P. Nesnídal, J. Stulík, P. Sebesta, Pulmonary polymethylmetacrylate embolism: a rare complication of percutaneous vertebroplasty, Acta Chir. Orthop. Traumatol. Cech 77 (2010) 337e340.
Contents lists available at ScienceDirect
International Journal of Surgery journal homepage: www.journal-surgery.net
Original research
The clinical efficacy of vertebroplasty on osteoporotic vertebral compression fracture: A meta-analysis Jing Tian a, Liangbi Xiang b, Dapeng Zhou b, Qingyu Fan a, Baoan Ma a, * a b
Department of Orthopedics, Tangdu Hospital of the Fourth Military Medical University, Xi'an 710038, Shannxi 710038, China Department of Orthopedics, General Hospital of Shenyang Military Area Command, Shenyang 110840, China
h i g h l i g h t s Efficacy of vertebroplasty on osteoporotic vertebral compression fracture (VCF) was accessed. Vertebroplasty had significant efficacy on pain relief in osteoporotic VCF. Vertebroplasty had similar adjacent vertebral fracture incidence with traditional treatment.
a r t i c l e i n f o
a b s t r a c t
Article history: Received 3 January 2014 Received in revised form 12 September 2014 Accepted 25 October 2014 Available online 28 October 2014
We investigated the clinical efficacy of vertebroplasty (VP) for the treatment of osteoporotic vertebral compression fracture (OVCF). We searched the online databases such as MEDLINE, EMBASE, EBSCO, Springer, Ovid and Cochrane library citations up to May 2012 and 5 eligible studies were included in this study. The meta-analysis was conducted using software RevMan 5.0. For the continuous data, the weighted mean difference (WMD) and its 95% confidence interval (CI) were calculated and the odds ratio (OR) and the corresponding 95% CI were calculated for the dichotomous data. The results demonstrated that the Visual Analogue Scale (VAS) score of patients treated with VP was significantly lower than that treated with traditional treatment at each time point (one week: WMD ¼ 2.55, 95% CI, 3.08 to 2.02, P < 0.0001; 12 weeks: WMD ¼ 0.90, 95% CI, 1.22 to 0.57, P < 0.0001; 24 weeks: WMD ¼ 1.75, 95% CI, 2.30 to 1.19, P < 0.0001; 48 weeks: WMD ¼ 1.75, 95% CI, 2.30 to 1.19, P < 0.001). For The incidence of adjacent vertebral fracture, the overall estimate (OR ¼ 2.06, 95% CI: 0.26 to 16.29, P ¼ 0.50) indicated that there was no statistically significant difference between VP and traditional treatment. In conclusion, the OVCF patients treated by VP had statistically significant improvements in pain relief compared with the traditional treatment and there was the similar incidence of adjacent vertebral fracture between the patients treated by VP and traditional treatment. © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
Keywords: Vertebroplasty Osteoporosis Vertebral compression fracture System assessment
1. Introduction Osteoporosis (porous bones) as a systemic skeletal disease, is characterized by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase of bone fragility and susceptibility to fractures [1]. Vertebral compression fracture (VCF) is the most common complication of osteoporosis [2]. The risk of VCF was increased with age [3]. Osteoporotic VCF (OVCF) is a leading cause of disability and morbidity in the elderly [4]. As the most common fractures in the elders with osteoporosis, it was
* Corresponding author. Department of Orthopedics, Tangdu Hospital of the Fourth Military Medical University, No.1 Xin'si Road, Xi'an 710038, Shannxi Province, China. E-mail address: [email protected] (B. Ma). http://dx.doi.org/10.1016/j.ijsu.2014.10.027 1743-9191/© 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
occurred in 20% of people older than 70 years and in 16% of postmenopausal women [5]. It was reported that there were more than 700,000 osteoporotic VCFs per year in the United States and approximately 85% of these fractures were due to primary osteoporosis [6]. Traditional treatments for the patients with OVCF include bed rest, oral or parenteral analgesics, muscle relaxants, external back bracing, and physical therapy [7]. Because the narcotic agents and a variety of expensive spinal orthoses are commonly used in the traditional treatment [8], the effectiveness of them may be limited due to the high cost and the long-time treatment. Thus, finding a treatment with high efficacy and low cost is a major task in clinical study for OVCF. Vertebroplasty (VP) is a minimally invasive technique in vertebral body lesion therapy. It was reported that VP could effectively
1250
J. Tian et al. / International Journal of Surgery 12 (2014) 1249e1253
treat pain and immobility which caused by VCF [9e12]. Although the efficacy and safety of VP is affirmed constantly [13e15], the disputes on the efficacy and complications of VP are still existed in recent studies. The study of Ploeg et al. reported that there were insufficient evidence to reliably assess efficacy of VP [16], while Blasco J et al. reported that VP achieved faster pain relief but was associated with a higher incidence in vertebral fractures. Therefore, we conducted a meta-analysis to statistically analyze the data from the recent studies in order to provide more reliable basis for the clinical efficacy of VP in treating OVCF. 2. Materials and methods 2.1. Search criteria and strategies We retrieved the databases such as MEDLINE, EMBASE, EBSCO, Springer, Ovid and Cochrane library up to May 2012. The keywords included “vertebroplasty”, “osteoporosis” and “vertebral compression fracture”. The studies should meet the following inclusion criteria: (1) researches were clinical randomized controlled trials (RCTs) related to VP in the treatment of OVCF; (2) studies were published abroad; (3) the patients in experimental group should be treated with VP and the patients in the control group were treated by the traditional treatment including bed rest, oral antiosteoporotic drugs and painkillers, wearing the spinal orthosis, reset, or functional exercise; (4) the Visual Analogue Scale (VAS) score for pain or/and complications were investigated. The studies were excluded if (1) the patients in the studies suffered cardiopulmonary dysfunction and other serious diseases, (2) there was no specific data except the curves of the indicators, (3) the patients were not confirmed by diagnosis and (4) the studies were nonRCTs. 2.2. Quality assessment and data extraction Two investigators independently assessed the study quality and extracted the data. Disagreements were resolved by discussion. The study quality was evaluated based on the random allocation method, blind method and evaluation of withdrawal. The extracted data included general information (first author, year and region) and study characteristics (design, follow-up time, sample size, age and gender of subjects and the data of outcomes). 2.3. Statistical analysis The meta-analysis was conducted using the Cochrane software RevMan 5.0. For continuous data, the weighted mean difference (WMD) and its 95% confidence interval (CI) were calculated. For dichotomous data, the odds ratio (OR) and the corresponding 95% CI were calculated. The Z-test was used for assessing the significance of the pooled OR and WMD, with P < 0.05 considered statistically significant. Heterogeneity among the included studies was evaluated by chi-square test and I2 statistic. If no significantly heterogeneity (P > 0.05 or I2 < 50%) was found, the effect size was pooled based on the fixed-effects model. Otherwise, randomeffects model was used.
one non-RCT and four literature which did not report the treatment of OVCF with VP were excluded. As a result, 5 literature were identified (Fig. 1). 3.2. Characteristics of included studies According to the inclusion and exclusion criteria, a total of five eligible studies [17e21] were included in this meta-analysis. The published year was ranged from 2007 to 2012. All the included subjects were elders aged over 50 years old. The duration of followup in these studies was ranged from 2 weeks to 36 months. All the included studies were RCTs. Among them, the study of Farrokhi et al. [18] was a single-blind RCT and the study of Rousing et al. [20] was a double-blind RCT. The other three studies did not define the blind method (Table 1). 3.3. Statistical analysis 3.3.1. Comparison of VAS score Two included studies [18,19] investigated the VAS score at one week after treatment. Fixed effects model was used because no significant heterogeneity was found (P ¼ 0.06, I2 ¼ 71%). The pooled estimate (WMD ¼ 2.55, 95% CI: 3.08 to 2.02, P < 0.00001) showed that there was statistically significant difference between the experimental and control group. The result indicated that the VAS score of the patients in VP group were significantly lower than that in control group at one week after treatment (Fig. 2A). The VAS score at 12 weeks after treatment was shown in two included studies [19,20]. There was no significant heterogeneity among the studies (P ¼ 0.18, I2 ¼ 44%), so fixed effects model was used. The pooled WMD (0.90, 95% CI: 1.22 to 0.57, P < 0.00001) showed that the statistically significant difference was existed between the two groups. It suggested that the VAS score of patients in VP group was significantly lower than that in control group at 12 weeks after treatment (Fig. 2B). Two included studies [18,19] involved in VAS score at 24 weeks after treatment. Fixed effects model was used for no significant heterogeneity between the studies (P ¼ 0.59, I2 ¼ 0%). The overall WMD was 1.75 (95% CI: 2.30 to 1.19, P < 0.00001), which showed the statistically significant difference between the two groups. It indicated that the VAS score of the patients in VP group was significantly lower compared with that in control group at 24 weeks after treatment (Fig. 2C). A total of three studies [18e20] showed the VAS score at 48 weeks after treatment. Fixed effects model was used for no significant heterogeneity among the studies (P ¼ 0.06, I2 ¼ 65%). The pooled estimate (WMD ¼ 1.12, 95% CI: 1.43 to 0.81, P < 0.00001) showed a statistically significant difference between
3. Results 3.1. Literature search After the initial search in the databases, a total of 1073 potentially relevant literature were identified. Then 12 articles were remained by omitting the duplicated and obviously irrelevant literature. Based on exclusion and inclusion criteria, two reviewers,
Fig. 1. The flow diagram of literature screening.
J. Tian et al. / International Journal of Surgery 12 (2014) 1249e1253
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Table 1 The characteristics of the included studies. First author
year
Region
Sample size Experiment/control
Age Experiment/control
Female (%) Experiment/control
Design
Duration of follow-up
Indicators
Blasco
2012
Europe
64/61
73/82
RCT
12 months
Farrokhi
2011
Asia
40/42
71.33 ± 9.95/ 75.27 ± 8.53 72 (59e90)/ 74 (55e87)
30/30
Single-blind RCT
36 months
Klazen
2010
Europe
75.2 ± 9$8/ 75.4 ± 8$4
69/69
RCT
12 months
Rousing
2009
Europe
97/93a 92/86b 89/81c 86/77d 23/23e 22/22f 23/22g
Adjacent vertebral fracture incidence VAS score at 1, 24 and 48 weeks after treatment, adjacent vertebral fracture incidence VAS score at 1, 12, 24 and 48 weeks after treatment
80 (65e96)/ 80 (71e93)
NA
Double-blind RCT
3 months
Voormolen
2007
Europe
18/16
72 (59e84)/ 74 (55e88)
14/14
RCT
Two weeks
VAS score at 12 and 48 weeks after treatment, adjacent vertebral fracture incidence Adjacent vertebral fracture incidence
NA: not provided; VAS: visual analogue scale; RCT: randomized controlled trial. a Sample size of Klazen et al. in the indicator of VAS score at 1 week after treatment. b Sample size of Klazen et al. in the indicator of VAS score at 12 week after treatment. c Sample size of Klazen et al. in the indicator of VAS score at 24 week after treatment. d Sample size of Klazen et al. in the indicator of VAS score at 48 week after treatment. e Sample size of Rousing et al. in the indicator of VAS score at 12 week after treatment. f Sample size of Rousing et al. in the indicator of VAS score at 48 week after treatment. g Sample size of Rousing et al. in the indicator of adjacent vertebral fracture incidence.
Fig. 2. Forest plots of VAS score after treatment. A: VAS score at one week after treatment; B: VAS score at 12 weeks after treatment; C: VAS score at 24 weeks after treatment; D: VAS score at 24 weeks after treatment.
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Fig. 3. Forest plots of the adjacent vertebral fracture incidence.
the experimental and control group. It suggested that the VAS score of the patients in VP group was significantly lower than that in control group at 48 weeks after treatment (Fig. 2D). 3.3.2. Comparison of complications Four included studies [17,18,20,21] reported the incidence of adjacent vertebral fracture after treatment. Significant heterogeneity (P ¼ 0.03; I2 ¼ 67%) was found among the studies, so random effects model was used. The overall estimate (OR ¼ 2.06, 95% CI: 0.26 to 16.29, P ¼ 0.50) indicated that there was no statistically significant difference between the two groups for the adjacent vertebral fracture incidence (Fig. 3). In addition, Farrokhi MR et al. observed that epidural cement leakage caused severe right lower-extremity pain and weakness in one patient [18]. Meanwhile, no other serious complications or adverse events were reported in all the included studies.
sample size was small. The result of this study may be questioned and more studies with large sample size were required to verify these result. Second, the publication bias was not assessed because of small number of included studies for each indicator. Third, random method of some trials was undefined. The results of this study may be affected by the different study designs of the included studies. Moreover, the sources of heterogeneity need to be explored in the further studies. 5. Conclusion Based on the result in this study, we concluded that the OVCF patients treated by VP had statistically significant improvements in pain relief and similar incidence of adjacent vertebral fracture compared with the traditional treatment. Ethical approval
4. Discussion Low back pain is the main symptom of OVCF, and long-term pain will seriously influence the life quality of the OVCF patients [22]. The causes of pain in OVCF patients are complicated, which may related to nerve endings irritated by slight movement of vertebral fracture [23e25]. In this study, the results showed that the VAS score of patients in VP group was significantly lower than that in traditional treatment group at each time point. It suggested the OVCF patients treated by VP had statistically significant improvements in pain relief. It was consistent with the result of other published studies [11,26,27]. The mechanism of VP in treating OVCF patients may be associated with the characteristics of VP and the causes of pain in OVCF patients. We speculated that, firstly, the curing material (usually polymethyl methacrylate) can fix the micro fractures, strengthen the vertebral body and relieve nerve irritation, then large amounts of heat is released with the concretion and agglomeration of polymethyl methacrylate and the temperature is increased [28,29]. The increase of temperature ascension, extrusion of the solid and chemical toxicity of the polymethyl methacrylate may lead to the necrosis of nerve endings, so as to relieve pain [30,31]. In addition, the present study showed no difference was found in the incidence of adjacent vertebral fracture between VP and traditional treatment group. Meanwhile, severe right lowerextremity pain and weakness caused by the leakage of cement was observed by Farrokhi MR et al. [18]. It has been reported that leakage of cement outside the vertebral body was markedly common in VP [16]. Although no other serious complications or adverse events were reported in all the included studies in this metaanalysis, some potentially rare complications such as pulmonary embolism caused by the leakage of cement can be devastating [32]. Therefore, more studies must be done to investigate the low incidence but high devastating complications. Some limitations of this meta-analysis should be mentioned. First, for each indicator, the number of the included studies and
None. Financial support None. Author contribution Study conception and design: Baoan Ma, Qingyu Fan. Acquisition of data: Jing Tian. Analysis and interpretation of data: Liangbi Xiang. Drafting the manuscript: Dapeng Zhou, Jing Tian, Critical revision of manuscript: Baoan Ma. Conflict of interest None. Acknowledgment This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. References [1] O. Johnell, J. Kanis, Epidemiology of osteoporotic fractures, Osteoporos. Int. 16 (2005) S3eS7. [2] F.M. Phillips, E. Ho, M. Campbell-Hupp, T. Mcnally, F.T. Wetzel, P. Gupta, Early radiographic and clinical results of balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures, Spine 28 (2003) 2260e2265. [3] J.L. Old, M. Calvert, Vertebral compression fractures in the elderly, Am. Fam. Physician (2004) 69. [4] F.M. Phillips, Minimally invasive treatments of osteoporotic vertebral compression fractures, Spine 28 (2003) S45eS53. [5] L. Cohen, Fractures of the osteoporotic spine, Orthop. Clin. North Am. 21 (1990) 143e150. [6] B.L. Riggs, L. Melton Iii, The worldwide problem of osteoporosis: insights afforded by epidemiology, Bone 17 (1995) S505eS511.
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