Controversial Issues in Cementoplasty
Kalliopi Alpantaki, MD¹ ; Michael Dohm, MD²; Georgios Vastardis, MD³; Alexander G. Hadjipavlou, MD⁴
¹ Department of Orthopaedic Surgery and Traumatology, University of Crete; Herakleion, Crete, Greece²Department of Orthopaedic Surgery, University of Arizona; Tucson, AZ, USA
³Iasso General Hospital; Athens, Greece
⁴Department of Orthopaedic Surgery and Rehabilitation, University of Texas Medical Branch; Galveston, TX, USA
Corresponding Author:Alexander G. Hadjipavlou, MD, Department of Orthopaedic Surgery & Rehabilitation, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555; ahadjipa@yahoo.com
DOI: 10.18600/toj.020203
INTRODUCTION
Since their inception, both vertebroplasty, introduced in the mid-80s [1], and balloon kyphoplasty, introduced in the late 90s [2], have become widespread methods for the treatment of osteoporotic vertebral compression fractures (OVCFs) and osteolytic tumors. However, by 2009, kyphoplasty and particularly vertebroplasty had been challenged as ineffective procedures by 2 randomized controlled trials (RCTs) published in the New England Journal of Medicine (NEJM) [3,4]. These 2 studies suggest that vertebroplasty is not significantly different to placebo. These assertions were widely accepted, reducing the practice of cementoplasty as they compared the procedure to a sham surgery under the same operating and anesthetic conditions. Widespread debate has ensued suggesting vertebroplasty is expensive and ineffectual. In September 2010, the American Academy of Orthopaedic Surgeons (AAOS) issued a strong recommendation against vertebroplasty and a weak recommendation for kyphoplasty [5]. Subsequently, an editorial in the NEJM Journal Watch by Brett concluded that selective and limited use of vertebroplasty is acceptable as long as the clinician shares uncertainty about the procedure’s effectiveness with the patient and intervention should be performed neither too early nor too late [6]. An extensive debate among critics has followed in the medical community raising serious concerns regarding the 2 RCTs and questioning their scientific integrity with regard to selection of patients with high patient refusal rate, lack of statistical power with high "sham group" crossover, treatment methodology, failure to analyze fracture type subgroups, and inclusion criteria with low pain scores [7-9]. This review addresses these issues. Age of fracture is a disputable factor. Contrary to reports indicating treatment response is not related to the age of fracture [10], more recent studies demonstrate that older fractures do not respond as well with vertebroplasty [11]. These 2 RCTs could have been stratified or perhaps limited to acute fractures. Aebi [9] has remarked that the character of the back pain should have been defined. Pain associated with OVCFs should be differentiated from facetogenic arthritic pain that can worsen or become provoked by segmental OVCF-related kyphosis that renders the spinal segment unstable. This pain may respond well with lasting effect [12] to facet-joint local anesthesia [13] or radiofrequency ablation. Rapid pain relief, after vertebroplasty and sham procedure alike, may result from the therapeutic response of the local anesthesia around the facet joint and not the placebo effect [8].
The effective amount of cement injected is questionable. Fill volumes of at least 13%‒16% of vertebral volume in 1 study and 24% in another are considered optimal for restoration of vertebral body strength [14,15]. A poly(methyl methacrylate) (PMMA) volume of 3 mL in the thoracolumbar spine in the Buchbinder study (no published cement data are available in the Kallmes study) instead of at least 4 mL can be considered inadequate for instituting optimal strength to axial loading [8]. Furthermore, the authors successfully revised 5 patients with failed painful cementoplasty, due to insufficient cement volume, with kyphoplasty in the lumbar spine (Figure 1).
The inclusion pain score was 3 out of 10 allowing the authors to recruit more patients. No mention was made by the authors as to why patients refused randomization. Pain severity may have influenced their decision-making [7,8,16]. It has been argued that both RCTs were underpowered (131 patients in 1 study and 78 in the other), with difficulty enrolling an adequate population sample. A substantial number of patients crossed over from the sham procedure to vertebroplasty.
It is of interest in these 2 RCTs that a subset of patients with pseudarthrosis and kyphosis (in particular patients on steroids), which are notoriously refractory to conservative treatment, were not included (Figure 2). These patients responded very well to kyphoplasty. Furthermore, it is well known [17] that a group of patients with osteoporotic fractures or pseudarthrosis may lead to crippling, painful kyphotic deformity (even while on conservative treatment) with potential neurologic deficit. These complications lead to major surgical intervention [18].
Comparing a surgical procedure to a sham procedure performed in an ethical fashion and well controlled is valuable. The degree of confidence, however, of these two RCTs is questionable as there are demonstrable flaws which should be evaluated further. Mandates and recommendations based on inadequate scientific evidence are currently being made and are unfortunately influencing decision-making regarding geriatric patients who could benefit from a reduction in pain and disability and improvement in quality of life through appropriate intervention. Clinical decision-making algorithms (guidelines) should include studies with incontrovertible scientific thoroughness and rigor based on large stratified population samples and continuously updated and modified based on the evidence.
Since their inception, both vertebroplasty, introduced in the mid-80s [1], and balloon kyphoplasty, introduced in the late 90s [2], have become widespread methods for the treatment of osteoporotic vertebral compression fractures (OVCFs) and osteolytic tumors. However, by 2009, kyphoplasty and particularly vertebroplasty had been challenged as ineffective procedures by 2 randomized controlled trials (RCTs) published in the New England Journal of Medicine (NEJM) [3,4]. These 2 studies suggest that vertebroplasty is not significantly different to placebo. These assertions were widely accepted, reducing the practice of cementoplasty as they compared the procedure to a sham surgery under the same operating and anesthetic conditions. Widespread debate has ensued suggesting vertebroplasty is expensive and ineffectual. In September 2010, the American Academy of Orthopaedic Surgeons (AAOS) issued a strong recommendation against vertebroplasty and a weak recommendation for kyphoplasty [5]. Subsequently, an editorial in the NEJM Journal Watch by Brett concluded that selective and limited use of vertebroplasty is acceptable as long as the clinician shares uncertainty about the procedure’s effectiveness with the patient and intervention should be performed neither too early nor too late [6]. An extensive debate among critics has followed in the medical community raising serious concerns regarding the 2 RCTs and questioning their scientific integrity with regard to selection of patients with high patient refusal rate, lack of statistical power with high "sham group" crossover, treatment methodology, failure to analyze fracture type subgroups, and inclusion criteria with low pain scores [7-9]. This review addresses these issues. Age of fracture is a disputable factor. Contrary to reports indicating treatment response is not related to the age of fracture [10], more recent studies demonstrate that older fractures do not respond as well with vertebroplasty [11]. These 2 RCTs could have been stratified or perhaps limited to acute fractures. Aebi [9] has remarked that the character of the back pain should have been defined. Pain associated with OVCFs should be differentiated from facetogenic arthritic pain that can worsen or become provoked by segmental OVCF-related kyphosis that renders the spinal segment unstable. This pain may respond well with lasting effect [12] to facet-joint local anesthesia [13] or radiofrequency ablation. Rapid pain relief, after vertebroplasty and sham procedure alike, may result from the therapeutic response of the local anesthesia around the facet joint and not the placebo effect [8].
The effective amount of cement injected is questionable. Fill volumes of at least 13%‒16% of vertebral volume in 1 study and 24% in another are considered optimal for restoration of vertebral body strength [14,15]. A poly(methyl methacrylate) (PMMA) volume of 3 mL in the thoracolumbar spine in the Buchbinder study (no published cement data are available in the Kallmes study) instead of at least 4 mL can be considered inadequate for instituting optimal strength to axial loading [8]. Furthermore, the authors successfully revised 5 patients with failed painful cementoplasty, due to insufficient cement volume, with kyphoplasty in the lumbar spine (Figure 1).
The inclusion pain score was 3 out of 10 allowing the authors to recruit more patients. No mention was made by the authors as to why patients refused randomization. Pain severity may have influenced their decision-making [7,8,16]. It has been argued that both RCTs were underpowered (131 patients in 1 study and 78 in the other), with difficulty enrolling an adequate population sample. A substantial number of patients crossed over from the sham procedure to vertebroplasty.
It is of interest in these 2 RCTs that a subset of patients with pseudarthrosis and kyphosis (in particular patients on steroids), which are notoriously refractory to conservative treatment, were not included (Figure 2). These patients responded very well to kyphoplasty. Furthermore, it is well known [17] that a group of patients with osteoporotic fractures or pseudarthrosis may lead to crippling, painful kyphotic deformity (even while on conservative treatment) with potential neurologic deficit. These complications lead to major surgical intervention [18].
Comparing a surgical procedure to a sham procedure performed in an ethical fashion and well controlled is valuable. The degree of confidence, however, of these two RCTs is questionable as there are demonstrable flaws which should be evaluated further. Mandates and recommendations based on inadequate scientific evidence are currently being made and are unfortunately influencing decision-making regarding geriatric patients who could benefit from a reduction in pain and disability and improvement in quality of life through appropriate intervention. Clinical decision-making algorithms (guidelines) should include studies with incontrovertible scientific thoroughness and rigor based on large stratified population samples and continuously updated and modified based on the evidence.
MATERIALS & METHODS
We performed a literature search using PubMed database with the following keywords: osteoporotic vertebral compression fractures, vertebroplasty, kyphoplasty, and cementoplasty. The most recent pertinent papers discussing complications related to OVCF, cement, and surgical technique were analyzed. RCTs comparing outcomes of vertebroplasty, kyphoplasty, and conservative treatment are examined.
RCTs
A recent, randomized double-blind placebo controlled trial by Clark et al. supported the effectiveness of vertebroplasty [19]. In this study, the authors demonstrated the immediate and 6 month sustained improvement with vertebroplasty in contrast to a sham procedure in a well controlled experiment. Some of the objections leveled at the previous control trials were addressed in this study which limited the selection of patients to an inclusion pain score of 7 or more out of 10 and an average volume of injected cement per segment of 7.5 mL (SD=2.8). It is of interest to underscore in this study the incidence of 3.3% (2 patients out of 79) of spinal cord compression from progressive vertebral body collapse in the control group. These cases highlight the risks associated with painful OVCFs.
In this context, several RCTs demonstrate the benefit of vertebroplasty or kyphoplasty over traditional conservative therapy (Table 1). There was no statistically significant difference of pain relief or disability between vertebroplasty and kyphoplasty [47,48]. Kyphoplasty demonstrated improvement of kyphotic angulation [49-51] and less cement leakage [52]. It is of interest that although some studies showed pain relief was similar between vertebroplasty and kyphoplasty, the functional improvement was better in kyphoplasty [53-55]. Since one expects pain relief to parallel the quality of life improvement, these results are obfuscating.
We performed a literature search using PubMed database with the following keywords: osteoporotic vertebral compression fractures, vertebroplasty, kyphoplasty, and cementoplasty. The most recent pertinent papers discussing complications related to OVCF, cement, and surgical technique were analyzed. RCTs comparing outcomes of vertebroplasty, kyphoplasty, and conservative treatment are examined.
RCTs
A recent, randomized double-blind placebo controlled trial by Clark et al. supported the effectiveness of vertebroplasty [19]. In this study, the authors demonstrated the immediate and 6 month sustained improvement with vertebroplasty in contrast to a sham procedure in a well controlled experiment. Some of the objections leveled at the previous control trials were addressed in this study which limited the selection of patients to an inclusion pain score of 7 or more out of 10 and an average volume of injected cement per segment of 7.5 mL (SD=2.8). It is of interest to underscore in this study the incidence of 3.3% (2 patients out of 79) of spinal cord compression from progressive vertebral body collapse in the control group. These cases highlight the risks associated with painful OVCFs.
In this context, several RCTs demonstrate the benefit of vertebroplasty or kyphoplasty over traditional conservative therapy (Table 1). There was no statistically significant difference of pain relief or disability between vertebroplasty and kyphoplasty [47,48]. Kyphoplasty demonstrated improvement of kyphotic angulation [49-51] and less cement leakage [52]. It is of interest that although some studies showed pain relief was similar between vertebroplasty and kyphoplasty, the functional improvement was better in kyphoplasty [53-55]. Since one expects pain relief to parallel the quality of life improvement, these results are obfuscating.
Clinical Indications for Cementoplasty
Osteoporotic Fractures
OVCFs, despite their ubiquitous nature, can give rise to complications, such as chronic back pain, disabling deformity, reduced pulmonary function, restriction for the abdominal and thoracic organs, pseudoarthroses, neurological complications and clinical depression [56,57]. Kyphoplasty is not the first line treatment for OVCFs. OVCFs can respond satisfactorily to conservative treatment including bed rest, analgesics, bracing, antiosteoporotic medication, or some combination of the above [58]. The primary indication for a cementoplasty procedure is severe, persistent pain at the level of the fracture site refractory to conservative treatment [59] and concomitant disability. Pain to palpation at the fracture site spinous process is a reliable test indicating pain-generating pathology [60].
The optimal intervention procedure time is debatable. Studies generally support earlier intervention [33], though satisfactory results have also been reported in later intervention [61]. The majority of acute OVCFs improve in the first 3 months, and early intervention may not be necessary; however, a late intervention may lead to an unfavorable outcome. Papanastasiou et al. proposed a therapeutic "window" of 7 weeks, with an exception of prompt intervention when progression of the wedging vertebral is detected in the thoracic spine [62]. In a retrospective study, 99 patients were divided into 3 groups to evaluate the results of balloon kyphoplasty performed at different times after injury. Patients in all 3 groups displayed significant pain relief [63].
Pseudoarthrosis – Kummell’s disease
Another indication for cement augmentation procedures is the presence of painful pseudoarthrosis complicating OVCFs as a result of osteonecrosis [64]. A variety of terms have been used to describe this pathology: intervertebral vacuum, cleft, delayed vertebral collapse, vertebral non-union [65]. Herman Kummell first described this entity in 1895 as a posttraumatic delayed collapse of the vertebral body resulting from osteonecrosis [64]. He postulated that even minimal trauma can cause damage to the nutrient vessels which sets in motion delayed collapse of the trabeculae and leads to nonunion [65]. After OVCF, persistent mobility may lead to cleft formation and release of vacuum gas within the cracks of the subchondral bone which may contribute to nonunion. Subsequently, the gas-filled cleft fills with fluid and necrotic granulation tissue, resulting in a characteristic MRI image [66]. Alcohol consumption, radiotherapy, and steroids have been identified as contributing factors [67]. Incidence is estimated to range between 7%‒37% [68] and may be noted after 6 months of conservative treatment [69]. The disease may result in sequelae, such as severe kyphosis and extrusion of a posterior bony fragment into the canal. This may compromise the neural elements of the spinal canal resulting in neurologic deficit [66]. Treatment options must take into account 3 main factors: the patient's symptoms, the degree of the kyphotic deformity, and the presence of neurologic deficit [70]. Conservative treatment with bracing and analgesics can be ineffective and is contraindicated in the presence of spinal cord compression [71] (Figure 3). As the majority of patients are of an advanced age, many authors have recommended minimal procedures, such as cement augmentation alone [72,73] or in combination with short segmental fixation as safe and effective management [74] (Figure 4). Cement augmentation alleviates pain and prevents further collapse of the vertebral body. Li and others recommend a more extended procedure if there is a severe kyphotic deformity [75,76]. Patients with severe spinal stenosis and cord compression without neurologic deficit can benefit from kyphoplasty as a stand-alone procedure. In this instance, the cement-inserting cannula must be placed into the cleft at the anterior 2/3 of the vertebral body, dynamic monitoring during cement filling is recommended, and the cement should be infused slowly in a very doughy state [77]. In a recent cohort study of 1-level Kummell’s disease, 12 patients, although initially displaying significant improvement of pain and deformity correction, at 6 months exhibited variable degrees of kyphotic deformity and pain [78]. Inadequate interdigitation of cement into the trabeculae is attributed to the insufficient outcome that particularly occurs with vertebroplasty. This complication may be overcome by using a special kyphoplasty osteotome (KYPHON Latitude IITM Curette, 8.0mm T-tip; Medtronic, Minnesota, MN, USA) to break the sclerotic margins of bone surrounding the osteonecrotic cavity. Following this, a KYPHON flat balloon is inserted as there is reduced height of the vertebral body, and the cement is inserted slowly in a more viscous state and interdigitates with the trabecular bone.
The optimal intervention procedure time is debatable. Studies generally support earlier intervention [33], though satisfactory results have also been reported in later intervention [61]. The majority of acute OVCFs improve in the first 3 months, and early intervention may not be necessary; however, a late intervention may lead to an unfavorable outcome. Papanastasiou et al. proposed a therapeutic "window" of 7 weeks, with an exception of prompt intervention when progression of the wedging vertebral is detected in the thoracic spine [62]. In a retrospective study, 99 patients were divided into 3 groups to evaluate the results of balloon kyphoplasty performed at different times after injury. Patients in all 3 groups displayed significant pain relief [63].
Pseudoarthrosis – Kummell’s disease
Another indication for cement augmentation procedures is the presence of painful pseudoarthrosis complicating OVCFs as a result of osteonecrosis [64]. A variety of terms have been used to describe this pathology: intervertebral vacuum, cleft, delayed vertebral collapse, vertebral non-union [65]. Herman Kummell first described this entity in 1895 as a posttraumatic delayed collapse of the vertebral body resulting from osteonecrosis [64]. He postulated that even minimal trauma can cause damage to the nutrient vessels which sets in motion delayed collapse of the trabeculae and leads to nonunion [65]. After OVCF, persistent mobility may lead to cleft formation and release of vacuum gas within the cracks of the subchondral bone which may contribute to nonunion. Subsequently, the gas-filled cleft fills with fluid and necrotic granulation tissue, resulting in a characteristic MRI image [66]. Alcohol consumption, radiotherapy, and steroids have been identified as contributing factors [67]. Incidence is estimated to range between 7%‒37% [68] and may be noted after 6 months of conservative treatment [69]. The disease may result in sequelae, such as severe kyphosis and extrusion of a posterior bony fragment into the canal. This may compromise the neural elements of the spinal canal resulting in neurologic deficit [66]. Treatment options must take into account 3 main factors: the patient's symptoms, the degree of the kyphotic deformity, and the presence of neurologic deficit [70]. Conservative treatment with bracing and analgesics can be ineffective and is contraindicated in the presence of spinal cord compression [71] (Figure 3). As the majority of patients are of an advanced age, many authors have recommended minimal procedures, such as cement augmentation alone [72,73] or in combination with short segmental fixation as safe and effective management [74] (Figure 4). Cement augmentation alleviates pain and prevents further collapse of the vertebral body. Li and others recommend a more extended procedure if there is a severe kyphotic deformity [75,76]. Patients with severe spinal stenosis and cord compression without neurologic deficit can benefit from kyphoplasty as a stand-alone procedure. In this instance, the cement-inserting cannula must be placed into the cleft at the anterior 2/3 of the vertebral body, dynamic monitoring during cement filling is recommended, and the cement should be infused slowly in a very doughy state [77]. In a recent cohort study of 1-level Kummell’s disease, 12 patients, although initially displaying significant improvement of pain and deformity correction, at 6 months exhibited variable degrees of kyphotic deformity and pain [78]. Inadequate interdigitation of cement into the trabeculae is attributed to the insufficient outcome that particularly occurs with vertebroplasty. This complication may be overcome by using a special kyphoplasty osteotome (KYPHON Latitude IITM Curette, 8.0mm T-tip; Medtronic, Minnesota, MN, USA) to break the sclerotic margins of bone surrounding the osteonecrotic cavity. Following this, a KYPHON flat balloon is inserted as there is reduced height of the vertebral body, and the cement is inserted slowly in a more viscous state and interdigitates with the trabecular bone.
Cement Leakage
A potentially harmful event of cement augmentation procedures is PMMA cement leakage. The cement may extravasate locally into the spinal canal, the intervertebral disk space, the foramina, or the paravertebral space or migrate distally through the epidural or vertebral venous system. Although cement leakage is well tolerated in the majority of cases, it is a cause of pulmonary and neurological complications [79] which can be catastrophic. An advantage of kyphoplasty over vertebroblasty is the creation of a cavity by the balloon which allows a viscous cement injection under reduced pressure. In addition, the balloon tamp compacts the trabecular bone which may seal potential osseous or venous leak pathways [80].
The risk of cement leakage during augmentation, as reported in a systematic review, ranges from 2.7%‒26.3% with kyphoplasty, as demonstrated on fluoroscopic studies, and an incidence of cement leakage with vertebroplasty ranging from 11.7%‒71.4% [17,81]. CT studies show an incidence 22.5%‒87.5% [81] with vertebroplasty. This echoes Yeom et al. CT study that cement leakage is more frequently observed on CT than radiographs [82], suggesting that the incidence of cement leakage observed during surgery is underestimated as seen on plain fluoroscopy. Cement leakages were classified into 3 types: through the basivertebral vein (type B), through the segmental vein (type S), and through a cortical defect (type C) [82]. Cement extravasation is related to the viscosity of the cement, the injection pressure, and the amount of cement. [2,83-86]. It has also been reported that the rate of cement leakage is related to the timing of the procedure [63]. In the fracture acute phase (less than 7 weeks), cracks in the cortex increase the risk of cement extravasation. In late intervention, the healing process may reduce diffusion of cement, but require cement to be injected under higher pressure which also may promote cement leakage [63].
A potentially harmful event of cement augmentation procedures is PMMA cement leakage. The cement may extravasate locally into the spinal canal, the intervertebral disk space, the foramina, or the paravertebral space or migrate distally through the epidural or vertebral venous system. Although cement leakage is well tolerated in the majority of cases, it is a cause of pulmonary and neurological complications [79] which can be catastrophic. An advantage of kyphoplasty over vertebroblasty is the creation of a cavity by the balloon which allows a viscous cement injection under reduced pressure. In addition, the balloon tamp compacts the trabecular bone which may seal potential osseous or venous leak pathways [80].
The risk of cement leakage during augmentation, as reported in a systematic review, ranges from 2.7%‒26.3% with kyphoplasty, as demonstrated on fluoroscopic studies, and an incidence of cement leakage with vertebroplasty ranging from 11.7%‒71.4% [17,81]. CT studies show an incidence 22.5%‒87.5% [81] with vertebroplasty. This echoes Yeom et al. CT study that cement leakage is more frequently observed on CT than radiographs [82], suggesting that the incidence of cement leakage observed during surgery is underestimated as seen on plain fluoroscopy. Cement leakages were classified into 3 types: through the basivertebral vein (type B), through the segmental vein (type S), and through a cortical defect (type C) [82]. Cement extravasation is related to the viscosity of the cement, the injection pressure, and the amount of cement. [2,83-86]. It has also been reported that the rate of cement leakage is related to the timing of the procedure [63]. In the fracture acute phase (less than 7 weeks), cracks in the cortex increase the risk of cement extravasation. In late intervention, the healing process may reduce diffusion of cement, but require cement to be injected under higher pressure which also may promote cement leakage [63].
Cement leakage is significant. Using proper surgical technique, the incidence of cement leakage can be markedly reduced. Correct placement of the balloon, cement viscosity, constant fluoroscopically controlled cementation, and proper cement volume minimize the risk of cement leakage. Recent reports advocate that sufficient cement volume to restore vertebral strength and achieve good clinical outcome should be substantial [87] as opposed to earlier reports that small cement volumes are adequate [88].
A technique called "egg shell" has been promoted to prevent cement leakage when the vertebral confinement is violated. [60,89]. In this instance, if a compromised vertebral wall is identified, the balloon should be immediately removed, followed by 1cc cement deployed and the reinsertion of the balloon into the injected cement. At this stage, the inserted balloon is reinflated until it abuts the compromised vertebral wall which seals the defect. The cement is allowed to harden, the balloon is removed, followed by a conventional kyphoplasty [60] (Figure 5).
Respiratory Effects and Hemodynamic Changes
Hemodynamic and respiratory complications, such as transient hypotension and degrease of oxygen saturation, have been widely reported during cement augmentation procedures. The exact incidence is not clear. The incidence may be underestimated as a respiratory decline during surgery in a geriatric patient may be attributed to preexisting pulmonary disease [90]. Cement embolism can be asymptomatic or symptomatic and presents with dyspnea, tachypnea, tachycardia, cyanosis, chest pain, coughing, and hemoptysis [91]. Aebli et al., in several animal studies, using different materials, showed that cement and fat embolism can cause serious cardiopulmonary deterioration during cement augmentation procedures [92-94]. Pulmonary embolism is correlated to an increased interosseous pressure during the procedure which forces fat, bone marrow, and PMMA particles into the epidural and vertebral venous system. There is also a decline of sympathetic tone associated with this process rather than to cement toxicity itself [95]. The viscosity and the amount of cement injected is a significant factor related to cement extravasation. Evidence supports this finding [86]. Some authors recommend against injecting more than 30 mL or more than 3 levels per session [96]. Augmentation of multiple levels has also been blamed for cardiovascular complications associated with simultaneous inflation of multiple balloons or simultaneous injection of multiple levels [83]. Intracardiac cement leakage is an extremely rare complication following kyphoplasty and vertebroplasty. There are only a few cases reported in the literature [97-99]. The consequences of intracardiac cement embolism are perforation of myocardium, pericardial tamponade, or pericardial perforation, which may cause chest pain, dyspnea, and shock [98]. Open heart surgery or catheterization is necessary in order to remove the cement fragment [99].
Respiratory Effects and Hemodynamic Changes
Hemodynamic and respiratory complications, such as transient hypotension and degrease of oxygen saturation, have been widely reported during cement augmentation procedures. The exact incidence is not clear. The incidence may be underestimated as a respiratory decline during surgery in a geriatric patient may be attributed to preexisting pulmonary disease [90]. Cement embolism can be asymptomatic or symptomatic and presents with dyspnea, tachypnea, tachycardia, cyanosis, chest pain, coughing, and hemoptysis [91]. Aebli et al., in several animal studies, using different materials, showed that cement and fat embolism can cause serious cardiopulmonary deterioration during cement augmentation procedures [92-94]. Pulmonary embolism is correlated to an increased interosseous pressure during the procedure which forces fat, bone marrow, and PMMA particles into the epidural and vertebral venous system. There is also a decline of sympathetic tone associated with this process rather than to cement toxicity itself [95]. The viscosity and the amount of cement injected is a significant factor related to cement extravasation. Evidence supports this finding [86]. Some authors recommend against injecting more than 30 mL or more than 3 levels per session [96]. Augmentation of multiple levels has also been blamed for cardiovascular complications associated with simultaneous inflation of multiple balloons or simultaneous injection of multiple levels [83]. Intracardiac cement leakage is an extremely rare complication following kyphoplasty and vertebroplasty. There are only a few cases reported in the literature [97-99]. The consequences of intracardiac cement embolism are perforation of myocardium, pericardial tamponade, or pericardial perforation, which may cause chest pain, dyspnea, and shock [98]. Open heart surgery or catheterization is necessary in order to remove the cement fragment [99].
Some methods have been used to minimize the risk of cardiovascular and pulmonary complications during kyphoplasty, particularly when undertaking a multiple level procedure [83]. There are considerations during patient positioning and anesthesia preparation. Patient prone position during surgery affects intra-abdominal (increased inferior vena cava pressure), along with intrathoracic, and intraosseous vertebral body pressures [100]. Higher venous pressure results in safer cement insertion by avoiding risks, such as fat, bone marrow, or cement embolization [101]. During general anesthesia, a transient elevation of intrathoracic and intra-abdominal pressures can be achieved when inflating the balloons or inserting the cement to minimize pulmonary embolism. Multilevel (over 3 levels) cement-balloon kyphoplasty can be safely executed under proper surgical and anesthetic technique [83]. Optimal balloon placement, positive pressure ventilation during balloon inflation, and cement filling with very slow insertion, more of highly viscous cement in the vertebral body under constant imaging control minimize the risk of local and intravascular cement leakage and embolic complications. Close cardiorespiratory monitoring is also mandatory. Cement injection should be terminated if cement leakage is detected during fluoroscopy [102]. Standard therapeutic protocol for pulmonary cement embolization has not been described. In general, treatment is not suggested for asymptomatic patients with small peripheral emboli. In the case of symptomatic or central embolism, the suggested recommendation consists of initiating anticoagulation treatment with heparin followed by Coumadin for 6 months [91].
Neurologic Complications
Catastrophic neurologic injuries, including complete paraplegia, have been reported after intracanal cement leakage. In the majority of cases, this event is well tolerated. Neurologic damage is attributed to both exothermal injury to neural structures and neurocompression [103]. Not all cement extravasation into the epidural space is associated with complication [2,84]. Patel et. al reported a series of 10 patients with neurologic injury after kyphoplasty. Patients developed neurologic deficit either acutely (<24h) or gradually with an average of 37.1 days (range 3‒112 days) postoperative. Most of these patients required revision open surgical intervention for treatment of their neurologic injury [104]. Epidural cement leakages may occur along 1 of the following pathways: the fracture line extending to the posterior wall of the vertebral body, the basivertebral foramina, the anterior internal venous plexus, or the needle tract. Cement viscosity is an important factor. Bone cement in a liquid low-viscosity state may extravasate rapidly into the spinal canal [103], particularly when injected under high pressure. Pedicle perforation or fracture during the procedure or posterior wall violation is considered a significant risk factor for intracanal cement leakage and neurologic complication [105]. Often epidural cement extravasation is subclinical and goes undetected unless a postoperative CT scan is performed [103].
Intraforaminal leakage can be associated with radiculopathy. Occasionally patients with neuroforaminal extravasation require surgical decompression. However, in most cases, the symptoms respond well to conservative treatment or local steroid injection [106]. Transient femoral neuropathy has also been reported after cement leak into paravertebral muscles [17].
Neurologic complications associated with cement leakage in kyphoplasty are avoided if the posterior vertebral body wall and the pedicles remain intact, along with using continuous biplane fluoroscopy and preservation of the medial pedicle wall [107,108].
Adjacent Fracture
There is controversy regarding the risk of a subsequent fracture with vertebral augmentation. Some authors suggest that the alteration of biomechanical balance caused by the cement filling can lead to a stress-shielding phenomenon on the adjacent vertebral bodies [109]. Others advocate that the strengthening of the vertebral body with cement and the correction of the kyphosis achieved by kyphoplasty prevent a secondary fracture [110]. The mechanism for adjacent vertebral fracture is not clear, but it is speculated that the increased stiffness of the augmented vertebra changes the biomechanics of load transfer to the adjacent vertebrae. Although it is difficult to determine the optimal amount of cement filling, it is possible that rigid augmentation may also provoke failure of the adjacent, nonaugmented level [111]. Lin et al. showed that more than 70% of patients who sustained a subsequent fracture after vertebroplasty had intradiscal cement leak. Cement extravasation into the disc may increase the risk of a secondary fracture due to alteration of disc flexibility [112]. Also, patients with predominantly lower bone density, larger balloon or cement volume, fissure fracture, steroid use, and absence of systemic antiosteoporosis therapy have an increased risk of contiguous vertebral compression fracture [113-115].
Many authors argue that adjacent fractures have also been reported in untreated patients suggesting that this is a result of the preexisting osteoporosis rather than the procedure itself [116]. Additionally, kyphotic deformity caused by untreated OVCFs is another predisposing factor for secondary fracture development as it transfers the center of gravity forward resulting in an increased forward-bending moment which subsequently enhances the load within the kyphotic angle. Therefore kyphosis reduction due to kyphoplasty is expected to lessen the risk of new fracture development [117] (Figures 6 and 7).
Neurologic complications associated with cement leakage in kyphoplasty are avoided if the posterior vertebral body wall and the pedicles remain intact, along with using continuous biplane fluoroscopy and preservation of the medial pedicle wall [107,108].
Adjacent Fracture
There is controversy regarding the risk of a subsequent fracture with vertebral augmentation. Some authors suggest that the alteration of biomechanical balance caused by the cement filling can lead to a stress-shielding phenomenon on the adjacent vertebral bodies [109]. Others advocate that the strengthening of the vertebral body with cement and the correction of the kyphosis achieved by kyphoplasty prevent a secondary fracture [110]. The mechanism for adjacent vertebral fracture is not clear, but it is speculated that the increased stiffness of the augmented vertebra changes the biomechanics of load transfer to the adjacent vertebrae. Although it is difficult to determine the optimal amount of cement filling, it is possible that rigid augmentation may also provoke failure of the adjacent, nonaugmented level [111]. Lin et al. showed that more than 70% of patients who sustained a subsequent fracture after vertebroplasty had intradiscal cement leak. Cement extravasation into the disc may increase the risk of a secondary fracture due to alteration of disc flexibility [112]. Also, patients with predominantly lower bone density, larger balloon or cement volume, fissure fracture, steroid use, and absence of systemic antiosteoporosis therapy have an increased risk of contiguous vertebral compression fracture [113-115].
Many authors argue that adjacent fractures have also been reported in untreated patients suggesting that this is a result of the preexisting osteoporosis rather than the procedure itself [116]. Additionally, kyphotic deformity caused by untreated OVCFs is another predisposing factor for secondary fracture development as it transfers the center of gravity forward resulting in an increased forward-bending moment which subsequently enhances the load within the kyphotic angle. Therefore kyphosis reduction due to kyphoplasty is expected to lessen the risk of new fracture development [117] (Figures 6 and 7).
In a 1-year follow-up study, kyphoplasty as an addition to medical treatment and when performed in appropriately selected, patients showed improvement in the occurrence of new vertebral fracture in individuals with primary osteoporosis [33]. Similarly, after 3 years in a prospective study, the incidence of new vertebral fractures after kyphoplasty was significantly reduced versus control. All patients received pharmacological antiosteoporotic treatment, analgesics, and physiotherapy. Pain and function were also improved in the study group [35]. A recent meta-analysis of 12 studies involving 1,328 patients (768 who underwent augmentation procedure with PMMA and 560 who received nonoperative treatment) revealed that the risk of adjacent vertebral body fracture was equivalent between cementoplasty (vertebroplasty and balloon kyphoplasty) and conservative treatment [118].
Rib Fractures
Rib and sternum fractures are an infrequent complication. A systematic review cited 8 studies that reported incidence ranges from 0.6%‒4.3% [81]. Improper patient positioning as well as leaning over the patient’s back during surgery may result in rib fractures [17,103,119]. We experienced a case in which a patient with a successful kyphoplasty procedure who was seriously compromised with severe pain from 4 rib fractures. This complication occurred when pressure was applied over the kyphotic deformity in order to reduce the wedged vertebra.
Infection
Postoperative infection is a rare but devastating complication of kyphoplasty. A few cases have been reported in the literature [120,121]. Ongoing back pain and/or neurologic complication are the predominant presenting symptoms. Staphylococcus aureus is the most common pathogen [122,123]. Tuberculous spondylitis has also been reported [124]. Several studies have claimed that infection after cementoplasty procedure is likely related to a prior systemic infection, an immunocompromised condition, or intraoperative contamination. Preoperative prophylactic antibiotic administration is recommended. Cement mixed with antibiotics has also been recommended in the cases with a previous infection or in immunocompromised patients [125]. In case of concurrent infection, the procedure must be postponed until the infection is controlled. Cementoplasty infection can be treated conservatively with a course of antibiotics based on antibiotic sensitivity testing [126]. Infection refractory to conservative treatment or recurrent infection should be treated with corpectomy, cement removal, and instrumented spinal reconstruction [125].
Radiation Exposure
Long-term low-dose radiation exposure has been associated with leukemia, and thyroid or other cancers [127]. Nonneoplastic effects of radiation include genetic mutation, cataract, and developmental malformation of the fetus [127]. Radiation exposure and associated risks during cement augmentation procedures may be considerable for the patient, the surgeon and the staff; and therefore, actions should be taken to minimize exposure [128]. Mroz et al. reported that during kyphoplasty, the exposure time was 5.7±2.0 minutes/vertebra for a 1-level, 3.9±0.8 minutes/vertebra for a 2-level, and 2.9±1.2 minutes/vertebra for a 3-level kyphoplasty. Surgeon exposure as measured by the protected dosimeter was less than the minimum reportable dose (<0.010 mSv). Exposure as measured by the unprotected dosimeter, which is equivalent to deep whole-body exposure, was 0.248±0.170 mSv/vertebra. Eye exposure was 0.271±0.200 mSv/vertebra, and the shallow exposure (hand/skin) was 0.273±0.200 mSv/vertebra. Hand exposure was 1.744±1.173 mSv/vertebra. Without eye or hand protection, total radiation exposure dose to these areas would exceed the occupational exposure limit after 300 cases per year [129]. Protection of the hands and the eyes of the surgeon by using proper safety equipment, including radiation safety gowns, thyroid shields, gloves, and lead glasses, is strongly recommended [130]. In a similar study, emphasis was given to the importance of surgeons wearing lead glove protection on their leading hands during percutaneous vertebroplasty procedures. This measure has resulted to a 75% reduction rate of exposure to radiation [131].
Measures to minimize radiation exposure during kyphoplasty involve the use of low-dose or pulsed fluoroscopy [132] and the use of simultaneous biplanar fluoroscopy. When an optimal setting has been found, it is continued throughout the procedure and radiation is not "wasted" readjusting to a second plane of view [133]. Patient and staff radiation exposure is closely associated with their distance from the fluoroscopy beam. The source-to-skin distance during the procedure should not be less than 35 cm [134]. Unprotected staff working less than 70 cm from a fluoroscopic beam receive significant amounts of radiation, whereas those working more than 91.4 cm from the beam receive an extremely low amount of radiation [135].
Cost
Cost effectiveness is a contentious issue. The cost effectiveness of vertebral augmentation techniques for OVCFs has been challenged [136,137]. A drawback of balloon kyphoplasty is the high cost of the instrumentation which has been estimated at 3500 euro per treated level, whereas for vertebroplasty the cost is approximately 500 euro per level [138,139]. There is an additional cost and risk of general anesthesia with kyphoplasty, although it can be performed using local anesthesia for 1 or 2 levels. Multiple levels are often under general anesthesia. Studies have not taken into consideration patients with neurologic and musculoskeletal problems associated with OVCFs. Osteoporotic compression fractures have been associated with a 15% higher mortality rate [140,141]. Even for the oldest patients, both procedures are considered to be cost effective in terms of cost per life-year gained [142]. Patients have been found to require primary care services at a rate 14 times greater than the general population in the first year after a symptomatic vertebral fracture [143]. Compared to conservative treatment, significant reduction in mortality and drift in social functionality in patients treated with balloon kyphoplasty was identified at 1-year follow-up in a prospective UK study [144]. A cost-effectiveness analysis of OVCFs treatment among 858,978 patients in the Medicare dataset (2005‒2008) demonstrated kyphoplasty as cost effective and cost saving compared with vertebroplasty [142]. Borse conducted a cost-utility analysis from a payer’s perspective using a Markov model to assess the cost utility of balloon kyphoplasty compared with vertebroplasty. They found that balloon kyphoplasty is associated with better utility and higher effectiveness compared with vertebroplasty [145].CONCLUSIONS
Based on the best available evidence in our review of the literature, it appears that both vertebroplasty and kyphoplasty are valuable procedures in the management of OVCFs. These minimally invasive surgical procedures are not without risk, but potential complications can be minimized. It is imperative to take caution and care with these procedures and identify and promote best practice. In a systematic review [17] analyzing several reports on OVCFs it appears that osteoporosis is not innocuous as it can be complicated with serious neurological deficit and pulmonary and social problems. One third of these patients develop variable degrees of back pain attributed to facet arthropathy, deformity, and pseudoarthrosis. In a recently published book "Ending Medical Reversals", the authors extensively criticized vertebroplasty as ineffective and a harmful medical practice [146]. The majority of studies we reviewed support cementoplasty. A recent RCT [19] exonerates vertebroplasty by demonstrating its superiority over sham procedure and the potentially serious complications of OVCFs [17].
Vertebroplasty is indicated for the uncomplicated OVCF in the first 3 months and appears a more cost-effective procedure. In the early post-fracture period, some reduction of the fracture with postural hyperextension can be accomplished. To minimize cement extravasation, the cement should be of higher viscosity and should be inserted slowly using the kyphoplasty cement bone fillers. Balloon kyphoplasty is indicated in older fractures, when postural reduction is not feasible, and in established pseudoarthrosis. In cases of indeterminate cement interdigitation which may not prevent anterior cement migration and loss of reduction, this procedure can be augmented by a short posterior transpedicular stabilization.
We believe that a well designed randomized controlled trial which includes stratification of patient morbidity metabolic bone activity, and vertebral fracture activity is needed at this point. Patients with OVCFs are likely to have comorbid conditions and the indication for intervention, optimal timing, and manner of cementoplasty is still indeterminate. REFERENCES
[1] Galibert P, Deramond H, Rosat P, Le Gars D. Preliminary note on the treatment of vertebral angioma by percutaneous acrylic vertebroplasty. Neurochirurgie. 1987;33(2):166-8.
[2] Lieberman IH, Dudeney S, Reinhardt MK, Bell G. Initial outcome and efficacy of kyphoplasty in the treatment of painful osteoporotic vertebral compression fractures. Spine. 2001;26(14):1631-8.
[3] Buchbinder R, Osborne RH, Ebeling PR, Wark JD, Mitchell P, Wriedt C, Graves S, Staples MP, Murphy B. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. N Engl J Med. 2009;361(6):557-68.
[4] Kallmes DF, Comstock BA, Heagerty PJ, Turner JA, Wilson DJ, et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med. 2009;361(6):569-79.
[5] American Academy of Orthopaedic Surgeons. The treatment of symptomatic osteoporotic spinal compression fractures guidelines and evidence report. http//www.aaos.org/research/guidelines/SCFguidline.pdf Last accessed 5 November 2016.
[6] Allan S. Brett. Vertebroplasty -1 year later. NEJM Journal Watch Sept 16, 2010.
[7] Noonan P. Randomized vertebroplasty trials: bad news or sham news? AJNR Am J Neuroradiol. 2009;30(10):1808-9.
[8] Smith SJ, Vlahos A, Sewall LE. An objection to the New England Journal of Medicine vertebroplasty articles. Can Assoc Radiol J. 2010;61(2):121-2.
[9] Aebi M. Vertebroplasty: about sense and nonsense of uncontrolled "controlled randomized prospective trials". Eur Spine J. 2009;18(9):1247-8.
[10] Kaufmann TJ, Jensen ME, Schweickert PA, Marx WF, Kallmes DF. Age of fracture and clinical outcomes of percutaneous vertebroplasty. JNR Am J Neuroradiol. 2001;22(10):1860-3.
[11] Ryu KS, Park C The prognostic factors influencing on the therapeutic effect of percutaneous vertebroplasty in treating osteoporotic vertebral compression fractures. J Korean Neurosurg Soc. 2009;45(1):16-23.
[12] Manchikanti L, Singh V, Falco FJ, Cash KA, Pampati V. Lumbar facet joint nerve blocks in managing chronic facet joint pain: one-year follow-up of a randomized, double-blind controlled trial: Clinical Trial NCT00355914. Pain Physician. 2008;11(2):121-32.
[13] Wilson DJ, Owen S, Corkill RA. Facet joint injections as a means of reducing the need for vertebroplasty in insufficiency fractures of the spine. Wilson Eur Radiol. 2011;21(8):1772-8.
[14] Boszczyk B. Volume matters: a review of procedural details of two randomized controlled vertebroplasty trials of 2009. Eur Spine J. 2010;19(11):1837-40.
[15] Nieuwenhuijse MJ, Bollen L, van Erkel AR, Dijkstra PD. Optimal intravertebral cement volume in percutaneous vertebroplasty for painful osteoporotic vertebral compression fractures. Spine (Phila Pa 1976). 2012;37(20):1747-55.
[16] Munk PL, Liu DM, Murphy KP, Baerlocher MO. Effectiveness of vertebroplasty: a recent controversy. Can Assoc Radiol J. 2009;60(4):170-1.
[17] Hadjipavlou AG, Tzermiadianos MN, Katonis PG, Szpalski M. Percutaneous vertebroplasty and balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures and osteolytic tumours. J Bone Joint Surg Br. 2005;87(12):1595-604.
[18] Hadjipavlou AG, Katonis PG, Tzermiadianos MN, Tsoukas GM, Sapkas G. Principles of management of osteometabolic disorders affecting the aging spine. Eur Spine J. 2003;12(Suppl 2):S113-31.
[19] Clark W, Bird P, Gonski P, Diamond TH, Smerdely P, McNeil HP, Schlaphoff G, Bryant C, Barnes E, Gebski V. Safety and efficacy of vertebroplasty for acute painful osteoporotic fractures (VAPOUR): a multicentre, randomized, double-blind, placebo-controlled trial. Lancet. 2016;388(10052):1408-16.
[20] Chen D, An ZQ, Song S, Tang JF, Qin H. Percutaneous vertebroplasty compared with conservative treatment in patients with chronic painful osteoporotic spinal fractures. J Clin Neurosci. 2014;21(3):473-7.
[21] Blasco J, Martinez-Ferrer A, Macho J, San Roman L, Pomés J, Carrasco J, Monegal A, Guañabens N, Peris P. 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 Miner Res. 2012;27(5):1159-66.
[22] Farrokhi MR, Alibai E, Maghami Z. Randomized controlled trial of percutaneous vertebroplasty versus optimal medical management for the relief of pain and disability in acute osteoporotic vertebral compression fractures. J Neurosurg Spine. 2011;14(5):561-9.
[23] Alvarez L, Alcaraz M, Pérez-Higueras A, Granizo JJ, de Miguel I, Rossi RE, Quiñones D. Percutaneous vertebroplasty: functional improvement in patients with osteoporotic compression fractures.Spine (Phila Pa 1976). 2006;31(10):1113-8.
[24] Diamond TH, Bryant C, Browne L, Clark WA. Clinical outcomes after acute osteoporotic vertebral fractures: a 2-year non-randomised trial comparing percutaneous vertebroplasty with conservative therapy. Med J Aust. 2006;184(3):113-7.
[25] Klazen CA, Lohle PN, de Vries J, Jansen FH, Tielbeek AV, Blonk MC, Venmans A, van Rooij WJ, Schoemaker MC, Juttmann JR, Lo TH, Verhaar HJ, van der Graaf Y, van Everdingen KJ, Muller AF, Elgersma OE, Halkema DR, Fransen H, Janssens X, Buskens E, Mali WP. Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomized trial. Lancet. 2010;376(9746):1085-92.
[26] Rousing R, Andersen MO, Jespersen SM, Thomsen K, Lauritsen J. Percutaneous vertebroplasty compared to conservative treatment in patients with painful acute or subacute osteoporotic vertebral fractures: three-month follow-up in a clinical randomized study. Spine (Phila Pa 1976). 2009;34(13):1349-54.
[27] Rousing R, Hansen KL, Andersen MO, Jespersen SM, Thomsen K, Lauritsen JM. Twelve-month follow-up in forty-nine patients with acute/semiacute osteoporotic vertebral fractures treated conservatively or with percutaneous vertebroplasty: a clinical randomized study. Spine (Phila Pa 1976). 2010;35(5):478-82.
[28] Voormolen MH1, Mali WP, Lohle PN, Fransen H, Lampmann LE, van der Graaf Y, Juttmann JR, Jansssens X, Verhaar HJ. Percutaneous vertebroplasty compared with optimal pain medication treatment: short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures. The VERTOS study. AJNR Am J Neuroradiol. 2007;28(3):555-60.
[29] Kroon F, Staples M, Ebeling PR, Wark JD, Osborne RH, Mitchell PJ, Wriedt CH, Buchbinder R Two-year results of a randomized placebo-controlled trial of vertebroplasty for acute osteoporotic vertebral fractures. J Bone Miner Res. 2014;29(6):1346-55.
[30] Comstock BA, Sitlani CM, Jarvik JG, Heagerty PJ, Turner JA, Kallmes DF. Investigational vertebroplasty safety and efficacy trial (INVEST): patient-reported outcomes through 1 year. Radiology. 2013;269(1):224-31.
[31] Yang EZ, Xu JG, Huang GZ, Xiao WZ, Liu XK, Zeng BF, Lian XF. Percutaneous Vertebroplasty Versus Conservative Treatment in Aged Patients With Acute Osteoporotic Vertebral Compression Fractures: A Prospective Randomized Controlled Clinical Study. Spine (Phila Pa 1976). 2016;41(8):653-60.
[32] Wardlaw D, Cummings SR, Van Meirhaeghe J, Bastian L, Tillman JB, Ranstam J, Eastell R, Shabe P, Talmadge K, Boonen S. Efficacy and safety of balloon kyphoplasty compared with non-surgical care for vertebral compression fracture (FREE): a randomised controlled trial. Lancet. 2009;373(9668):1016-24.
[33] Grafe IA, Da Fonseca K, Hillmeier J, Meeder PJ, Libicher M, Nöldge G, Bardenheuer H, Pyerin W, Basler L, Weiss C, Taylor RS, Nawroth P, Kasperk C. Reduction of pain and fracture incidence after kyphoplasty: 1-year outcomes of a prospective controlled trial of patients with primary osteoporosis. Osteoporos Int. 2005;16(12):2005-12.
[34] Kasperk C, Hillmeier J, Nöldge G, Grafe IA, Dafonseca K, Raupp D, Bardenheuer H, Libicher M, Liegibel UM, Sommer U, Hilscher U, Pyerin W, Vetter M, Meinzer HP, Meeder PJ, Taylor RS, Nawroth P. Treatment of painful vertebral fractures by kyphoplasty in patients with primary osteoporosis: a prospective nonrandomized controlled study. J Bone Miner Res. 2005;20(4):604-12.
[35] Kasperk C, Grafe IA, Schmitt S, Nöldge G, Weiss C, Da Fonseca K, Hillmeier J, Libicher M, Sommer U, Rudofsky G, Meeder PJ, Nawroth P. Three-year outcomes after kyphoplasty in patients with osteoporosis with painful vertebral fractures. J Vasc Interv Radiol. 2010;21(5):701-9.
[36] Boonen S, Van Meirhaeghe J, Bastian L, Cummings SR, Ranstam J, Tillman JB, Eastell R, Talmadge K, Wardlaw D. Balloon kyphoplasty for the treatment of acute vertebral compression fractures: 2-year results from a randomized trial. J Bone Miner Res. 2011;26(7):1627-37.
[37] Xie E, Hao DJ, Yang TM, et al. Percutaneous kyphoplasty versus conservative treatment of acute and subacute osteoporotici vertebral compression fractures: a randomized controlled study. Chin J Orthop Trauma. 2011;13:719-24.
[38] Grohs JG, Matzner M, Trieb K, Krepler P. Minimal invasive stabilization of osteoporotic vertebral fractures: a prospective nonrandomized comparison of vertebroplasty and balloon kyphoplasty. J Spinal Disord Tech. 2005;18(3):238-42.
[39] Liu JT, Liao WJ, Tan WC, Lee JK, Liu CH, Chen YH, Lin TB. Balloon kyphoplasty versus vertebroplasty for treatment of osteoporotic vertebral compression fracture: a prospective, comparative, and randomized clinical study. Osteoporos Int. 2010;21(2):359-64.
[40] Lovi A, Teli M, Ortolina A, Costa F, Fornari M, Brayda-Bruno M. Vertebroplasty and kyphoplasty: complementary techniques for the treatment of painful osteoporotic vertebral compression fractures. A prospective non-randomised study on 154 patients. Eur Spine J. 2009;18(Suppl 1):95-101.
[41] De Negri P, Tirri T, Paternoster G, Modano P. Treatment of painful osteoporotic or traumatic vertebral compression fractures by percutaneous vertebral augmentation procedures: a nonrandomized comparison between vertebroplasty and kyphoplasty. Clin J Pain. 2007;23(5):425-30.
[42] Bae H, Shen M, Maurer P, Peppelman W, Beutler W, Li;itz R, Westerlund E, Peppers T, Lieberman I, Kim C, Girardi F. Clinical experience using Cortoss for treating vertebral compression fractures with vertebroplasty and kyphoplasty: 24-month follow-up. Spine (Phila Pa 1976). 2010;35(20):E1030-6.
[43] Kumar K, Nguyen R, Bishop S. A comparative analysis of the results of vertebroplasty and kyphoplasty in osteoporotic vertebral compression fractures. Neurosurgery. 2010;67(Suppl 3):171-88.
[44] Röllinghoff M, Siewe J, Zarghooni K, Sobottke R, Alparslan Y, Eysel P, Delank KS. Effectiveness, security and height restoration on fresh compression fractures—a comparative prospective study of vertebroplasty and kyphoplasty. Minim Invasive Neurosurg. 2009;52(5-6):233-7.
[45] Santiago FR1, Abela AP, Alvarez LG, Osuna RM, García M. Pain and functional outcome after vertebroplasty and kyphoplasty. A comparative study. Eur J Radiol. 2010;75(2):e108-13.
[46] Schofer MD, Efe T, Timmesfeld N, Kortmann HR, Quante M. Comparison of kyphoplasty and vertebroplasty in the treatment of fresh vertebral compression fractures. Arch Orthop Trauma Surg. 2009;129(10):1391-9.
[47] Dohm M, Black CM, Dacre A, Tillman JB, Fueredi G; KAVIAR investigators. A randomized trial comparing balloon kyphoplasty and vertebroplasty for vertebral compression fractures due to osteoporosis. AJNR Am J Neuroradiol. 2014;35(12):2227-36.
[48] Omidi-Kashani F, Samini F, Hasankhani EG, Kachooei AR, Toosi KZ, Golhasani-Keshtan F. Does percutaneous kyphoplasty have better functional outcome than vertebroplasty in single level osteoporotic compression fractures? A comparative prospective study. J Osteoporos. 2013;2013,690329.
[49] Muijs SPJ, Nieuwenhuijse MJ, van Erkel AR, Dijkstra PDS. Percutaneous vertebroplasty for the treatment of osteoporotic vertebral compression fractures: evaluation after 36 months. J Bone Joint Surg Br. 2009;91(3):379-84.
[50] Müller CW, Lange U, van Meirhaeghe J, Wardlaw D, Bastian L, Boonen S, Krettek C. An international multicenter randomized comparison of balloon kyphoplasty and nonsurgical care in patients with acute vertebral body compression fractures Eur Spine J. 2007;16:1977.
[51] Van Meirhaeghe J, Bastian L, Boonen S, Ranstam J, Tillman JB, Wardlaw D; FREE investigators. A randomized trial of balloon kyphoplasty and nonsurgical management for treating acute vertebral compression fractures: vertebral body kyphosis correction and surgical parameters. Spine (Phila Pa 1976). 2013;38(12):971-83.
[52] Kim KH, Kuh SU, Chin DK, Jin BH, Kim KS, Yoon YS, Cho YE. Kyphoplasty versus vertebroplasty: restoration of vertebral body height and correction of kyphotic deformity with special attention to the shape of the fractured vertebrae. J Spinal Disord Tech. 2012;25(6):338–44.
[53] Guo JB, Zhu Y, Chen BL, Xie B, Zhang WY, Yang YJ, Yue YS, Wang XQ. Surgical versus non-surgical treatment for vertebral compression fracture with osteopenia: a systematic review and meta-analysis. PLoS One. 2015;10(5):e0127145.
[54] Yuan WH, Hsu HC, Lai KL. Vertebroplasty and balloon kyphoplasty versus conservative treatment for osteoporotic vertebral compression fractures. A meta-analysis. Medicine (Baltimore). 2016;95(31):e4491.
[55] Papanastassiou ID, Phillips FM, Van Meirhaeghe J, Berenson JR, Andersson GB, Chung G, et al. Comparing effects of kyphoplasty, vertebroplasty, and non-surgical management in a systematic review of randomized and non-randomized controlled studies. Eur Spine J. 2012;21(9):1826-43.
[56] Arciero RA, Leung KY, Pierce JH. Spontaneous unstable burst fracture of the thoracolumbar spine in osteoporosis. a report of two cases. Spine (Phila Pa 1976). 1989;14(1):114-7.
[57] Cook DJ, Guyatt GH, Adachi JD, Clifton J, Griffith LE, Epstein RS, Juniper EF. Quality of life issues in women with vertebral fractures due to osteoporosis. Arthritis Rheum. 1993;36(6):750-6.
[58] Papadokostakis G, Damilakis J, Mantzouranis E, Katonis P, Hadjipavlou A. The effectiveness of calcitonin on chronic back pain and daily activities in postmenopausal women with osteoporosis. Eur Spine J. 2006;15(3):356-62.
[59] Robinson Y, Heyde CE, Försth P, Olerud C. Kyphoplasty in osteoporotic vertebral compression fractures—guidelines and technical considerations. J Orthop Surg Res. 2011;6:43.
[60] Gaitanis IN, Hadjipavlou AG, Katonis PG, Tzermiadianos MN, Pasku DS, Patwardhan AG. Balloon kyphoplasty for the treatment of pathological vertebral compressive fractures. Eur Spine J. 2005;14(3):250-60.
[61] Crandall D, Slaughter D, Hankins PJ, Moore C, Jerman J. Acute versus chronic vertebral compression fractures treated with kyphoplasty: early results. Spine J. 2004;4(4):418-24.
[62] Papanastassiou ID, Filis A, Aghayev K, Kokkalis ZT, Gerochristou MA, Vrionis FD. Adverse prognostic factors and optimal intervention time for kyphoplasty/vertebroplasty in osteoporotic fractures. Biomed Res Int. 2014;2014:925683.
[63] Oh GS, Kim HS, Ju CI, Kim SW, Lee SM, Shin H. Comparison of the results of balloon kyphoplasty performed at different times after injury. J Korean Neurosurg Soc. 2010;47(3):199-202.
[64] Kümmell H. Die rarefizierende Ostitis der Wirbelkörper. Deutsche Med. 1895;21180-1.
[65] Jindal N, Sharma R, Jindal R, Garg SK. Kummell’s disease: literature update and challenges ahead. Hard Tissue. 2013;2(5):45.
[66] Yang H, Pan J, Wang G Benefits from kyphoplasty. A review of osteoporotic vertebral fracture nonunion management. Spine (Phila Pa 1976). 2014;39(26):B4-6.
[67] Osterhouse MD, Kettner NW. Delayed posttraumatic vertebral collapse with intravertebral vacuum cleft. J Manipulative Physiol Ther. 2002;25(4):270-5.
[68] Freedman BA, Heller JG. Kummel disease: a not-so-rare complication of osteoporotic vertebral compression fractures. J Am Board Fam Med. 2009;22(1):75-8.
[69] Tsujio T, Nakamura H, Terai H, Hoshino M, Namikawa T, Matsumura A, et al. Characteristic radiographic or magnetic resonance images of fresh osteoporotic vertebral fractures predicting potential risk for nonunion: a prospective multicenter study. Spine (Phila Pa 1976). 2011;36(15):1229-35.
[70] Young WF, Brown D, Kendler A, Clements D. Delayed post-traumatic osteonecrosis of a vertebral body (Kummell's disease) Acta Orthop Belg. 2002;68(1):13–19.
[71] Nickell LT, Schucany WG, Opatowsky MJ. Kummell disease. Proc (Bayl Univ Med Cent). 2013;26(3):300-1.
[72] Zhang GQ, Gao YZ, Chen SL, Ding S, Gao K, Wang HQ. Comparison of percutaneous vertebroplasty and percutaneous kyphoplasty for the management of Kümmell's disease: A retrospective study. Indian J Orthop. 2015;49(6):577-82.
[73] Yang H, Gan M, Zou J, Mei X, Shen X, Wang G, Chen L. Kyphoplasty for the treatment of Kümmell's disease. Orthopedics. 2010;33(7):479.
[74] Chen L, Dong R, Gu Y, Feng Y. Comparison between Balloon Kyphoplasty and Short Segmental Fixation Combined with Vertebroplasty in the Treatment of Kümmell’s Disease. Retrospective Evaluation. Pain Physician 2015;18;373-81.
[75] Li KC, Wong TU, Kung FC, Li A, Hsieh CH. Staging of Kummel’s disease. J Musculoskeletal Res. 2004;8:43-55.
[76] Mochida J, Toh E, Chiba M, Nishimura K. Treatment of osteoporotic late collapse of a vertebral body of thoracic and lumbar spine. J Spinal Disord. 2001;14(5):393-8.
[77] Chen GD, Lu Q, Wang GL, Zou J, Yang HL, Yang Y, Luo ZP. Percutaneous Kyphoplasty for Kummell’s Disease with Severe Spinal Canal Stenosis Retrospective Study. Pain Physician 2015;18;E1021-8.
[78] Kim P, Kim SW. Balloon Kyphoplasty: An Effective Treatment for Kummell Disease? Korean J Spine. 2016;13(3):102-6.
[79] Hulme PA, Krebs J, Ferguson SJ, Berlemann U: Vertebroplasty and kyphoplasty: a systematic review of 69 clinical studies. Spine. 2006;31:1983-2001.
[80] Phillips FM, Wetzel TF, Lieberman I, Campbell-Hupp M. An in vivo comparison of the potential for extravertebral cement leak after vertebroplasty and kyphoplasty. Spine, 2002;27:2173-9.
[81] Tzermiadianos MN, Zindrick MR, Patwardhan AG, Katonis PG, Hadjipavlou AG. The Safety and Effectiveness of Percutaneous Vertebroplasty and Kyphoplasty in Osteoporotic Fractures and Tumors WSJ. 2007;2(2):64-94
[82] Yeom JS, Kim WJ, Choy WS, Lee CK, Chang BS, Kang JW. Leakage of cement in percutaneous transpedicular vertebroplasty for painful osteoporotic compression fractures. J Bone Joint Surg Br. 2003;85: 83-9.
[83] Katonis P, Hadjipavlou A, Souvatzis X, Tzermiadianos M, Alpantaki K, Simmons JW. Respiratory effects, hemodynamic changes and cement leakage during multilevel cement balloon kyphoplasty. Eur Spine J. 2012;21(9):1860-6.
[84] Dudeney S, Lieberman IH, Reinhardt MK, Hussein M. Kyphoplasty in the treatment of osteolytic vertebral compression fractures as a result of multiple myeloma. J Clin Oncol. 2002;20:2382-7.
[85] Lee B, Lee S, Yoo T. Paraplegia as a complication of percutaneous vertebroplasty with polymethylmethacrylate: a case report. Spine. 2002;27:419-22.
[86] Bohner M, Gasser B, Baroud G, Heini P. Theoretical and experimental model to describe the injection of a polymethylmethacrylate cement into a porous structure. Biomaterials 2003;24:2721-30.
[87] Röder C, Boszczyk B, Perler G, Aghayev E, Külling F, Maestretti G. Cement volume is the most important modifiable predictor for pain relief in BKP: results from SWISS spine, a nationwide registry. Eur Spine J. 2013;22(10):2241-8.
[88] Liebschner MA, Rosenberg WS, Keaveny TM. Effects of bone cement volume and distribution on vertebral stiffness after vertebroplasty. Spine (Phila Pa 1976). 2001;26(14):1547-54.
[89] Greene DL, Isaac R, Neuwirth M, Bitan FD: The eggshell technique for prevention of cement leakage during kyphoplasty. J Spinal Disord Tech. 2007;20:229-32.
[90] Groen RJ, Toit DF, Phillips FM, Hoogland PV, Kuizenga K, Coppes MH, Muller CJ, Grobbelaar M, Mattyssen J. Anatomical and pathological considerations in percutaneous vertebroplasty and kyphoplasty: a reappraisal of the vertebral venous system. Spine (Phila Pa 1976). 2004;29(13):1465-71.
[91] Krueger A, Bliemel C, Zettl R, Ruchholtz S. Management of pulmonary cement embolism after percutaneous vertebroplasty and kyphoplasty: a systematic review of the literature Eur Spine J. 2009;18(9):1257-65.
[92] Krebs J, Aebli N, Goss BG, Wilson K, Williams R, Ferguson SJ. Cardiovascular changes after pulmonary cement embolism: an experimental study in sheep. AJNR Am J Neuroradiol. 2007;28(6):1046-50.
[93] Aebli N, Krebs J, Davis G, Walton M, Williams MJ, Theis JC. Fat embolism and acute hypotension during vertebroplasty: an experimental study in sheep. Spine (Phila Pa 1976). 2002;27(5):460-6.
[94] Krebs J, Aebli N, Goss BG, Sugiyama S, Bardyn T, Boecken I, Leamy PJ, Ferguson SJ.J Cardiovascular changes after pulmonary embolism from injecting calcium phosphate cement. Biomed Mater Res B Appl Biomater. 2007;82(2):526-32.
[95] Aebli N, Krebs J, Schwenke D, Davis G, Theis JC. Pressurization of vertebral bodies during vertebroplasty causes cardiovascular complications: an experimental study in sheep. Spine (Phila Pa 1976). 2003;28(14):1513-20.
[96] Coumans JV, Reinhardt MK, Lieberman IH. Kyphoplasty for vertebral compression fractures: 1-year clinical outcomes from a prospective study. J Neursurg Spine. 2003;99:44-50.
[97] Audat ZA, Alfawareh MD, Darwish FT , Alomari AA. Intracardiac leakage of cement during kyphoplasty and vertebroplasty: a case report. Am J Case Rep. 2016;17:326-30.
[98] Kim MN, Jung JS, Kim SW, Kim YH, Park SM, Shim WJ. A sword-like foreign body lodged in the ventricular septum: A rare complication of percutaneous vertebroplasty. Eur Heart J. 2010;31(8):1006.
[99] Grifka RG, Tapio J, Lee KJ. Transcatheter retrieval of an embolized methylmethacrylate glue fragment adherent to the right atrium using bidirectional snares. Catheter Cardiovasc Interv. 2013;81(4):648-50.
[100] Theron J, Moret J. Spinal phlebography. Lumbar and cervical techniques. Berlin: Springer-Verlag. 1978.
[101] Vogelsang H. Intraosseous spinal venography. Amsterdam: Excerpta Medica. 1970.
[102] Souvatzis X, Alpantaki K, Hadjipavlou A. Re: Tran I, Gerckens U, Remig J, et al. First report of a life-threatening cardiac complication after percutaneous balloon kyphoplasty. Spine (Phila Pa 1976). 2013;38:E316-8. Spine (Phila Pa 1976). 2013;38(19):1709.
[103] Teng MM, Cheng H, Ho DM, Chang CY. Intraspinal leakage of bone cement after vertebroplasty: a report of 3 cases. AJNR Am J Neuroradiol. 2006;27(1):224-9.
[104] Patel AA, Vaccaro AR, Martyak GG, Harrop JS, Albert TJ, Ludwig SC, Youssef JA, Gelb DE, Mathews HH, Chapman JR, Chung EH, Grabowski G, Kuklo TR, Hilibrand AS, Anderson DG. Neurologic deficit following percutaneous vertebral stabilization. Spine (Phila Pa 1976). 200;32(16):1728-34.
[105] Becker S, Meissner J, Tuschel A, Chavanne A, Ogon M. Cement leakage into the posterior spinal canal during balloon kyphoplasty: a case report. J Orthop Surg (Hong Kong). 2007;15(2):222-5.
[106] Cotten A, Dewatre F, Cortet B, Assaker R, Leblond D, Duquesnoy B, Chastanet P, Clarisse J. Percutaneous vertebroplasty for osteolytic metastases and myeloma: effects of the percentage of lesion filling and the leakage of methyl methacrylate at clinical follow-up. Radiology. 1996;200(2):525-30.
[107] Park SY, Modi HN, Suh SW, Hong JY, Noh W, Yang JH. Epidural cement leakage through pedicle violation after balloon kyphoplasty causing paraparesis in osteoporotic vertebral compression fractures: a report of two cases. J Orthop Surg Res. 2010;5:54.
[108] Papaioannou I, Baikousis A, Korovessis P. Calcium Phosphate Cement Leakage during Balloon Kyphoplasty Causing Incomplete Paraplegia: Case Report and Review of the Literature. J Orthop Spine Trauma. 2016;2(3):e8894.
[109] Robinson Y, Tschöke SK, Stahel PF, Kayser R, Heyde CE.P. Complications and safety aspects of kyphoplasty for osteoporotic vertebral fractures: a prospective follow-up study in 102 consecutive patients. Patient Saf Surg. 2008;2:2.
[110] Faloon MJ, Ruoff M, Deshpande C, Hohman D, Dunn C, Beckloff N, Patel DV. Risk factors associated with adjacent and remote-level pathologic vertebral compression fracture following balloon kyphoplasty: 2-year follow-up comparison versus conservative treatment. J Long Term Eff Med Implants. 2015;25(4):313-9.
[111] Berlemann U, Ferguson S. J, Nolte LP, Heini PF, Adjacent vertebral failure after vertebroplasty. J Bone Joint Surg. Br. 202;84(5):748-52.
[112] Lin EP, Ekholm S, Hiwatashi A, Westesson PL. Vertebroplasty: cement leakage into the disc increases the risk of new fracture of adjacent vertebral body. Am J Neuroradiol. 2004;25:175-80.
[113] Yang S, Liu Y, Yang H, Zou J. Risk factors and correlation of secondary adjacent vertebral compression fracture in percutaneous kyphoplasty. Int J Surg. 2016;36(Pt A):138-42.
[114] Jian Wu, Yuehong Guan, Shengli Fan Analysis of risk factors of secondary adjacent vertebral fracture after percutaneous kyphoplasty. Biomedical Research 2017;28 (5):1956-61.
[115] Harrop JS, Prpa B, Reinhardt MK, Lieberman I. Primary and secondary osteoporosis' incidence of subsequent vertebral compression fractures after kyphoplasty. Spine (Phila Pa 1976). 2004;29(19):2120-5.
[116] Mukherjee S, Lee Y-P. Current Concepts in the Management of Vertebral Compression Fractures. Operative Techniques in Orthopaedics. 2011;21(3):251-60.
[117] Gaitanis IN, Carandang G, Phillips FM, Magovern B, Ghanayem AJ, Voro; LI, Havey RM, Zindrick MR, Hadjipavlou AG, Patwardhan AG. Restoring geometric and loading alignment of the thoracic spine with a vertebral compression fracture: effects of balloon (bone tamp) inflation and spinal extension. Spine J. 2005;5(1):45-54.
[118] Zhang H, Xu C, Zhang T, Gao Z, Zhang T. Does percutaneous vertebroplasty or balloon kyphoplasty for osteoporotic vertebral compression fractures increase the incidence of new vertebral fractures? A meta-analysis. Pain Physician. 2017;20(1):E13-28.
[119] Layton KF, Thielen KR, Koch CA, Luetmer PH, Lane JI, Wald JT, Kallmes DF. Vertebroplasty, first 1000 levels of a single center: evaluation of the outcomes and complications. AJNR Am J Neuroradiol. 2007;28(4):683-9.
[120] Yu SW, Chen WJ, Lin WC, Chen YJ, Tu YK. Serious pyogenic spondylitis following vertebroplasty: a case report. Spine (Phila Pa 1976). 2004;29(10):E209-21.
[121] Vats HS, McKiernan FE. Infected vertebroplasty: case report and review of literature. Spine (Phila Pa 1976). 2006;31(22):E859-62.
[122] Kallmes DF, Schweickert PA, Marx WF, Jensen ME. Vertebroplasty in the mid- and upper thoracic spine. AJNR Am J Neuroradiol. 2002;23(7):1117-20.
[123] Abdelrahman H, Siam AE, Shawky A, Ezzati A, Boehm H. Infection after vertebroplasty or kyphoplasty. A series of nine cases and review of literature. Spine J. 2013;13(12):1809-17.
[124] Kim HJ, Shin DA, Cho KG, Chung SS. Late onset tuberculous spondylitis following kyphoplasty: a case report and review of the literature. Korean J Spine. 2012;9(1):28-31.
[125] Ha KY, MD, Kim KW, Kim YH, MD, Oh IS, Park SW. Revision surgery after vertebroplasty or kyphoplasty. Clin Orthop Surg. 2010;2(4):203-8.
[126] Schmid KE, Boszczyk BM, Bierschneider M, Zarfl A, Robert B, Jaksche H. Spondylitis following vertebroplasty: a case report. Eur Spine J. 2005;14(9):895-9.
[127] Siddiqui SS, Jha A, Konar N, Ranganathan P, Deshpande DD, Divatia JV. Radiation exposure among medical professionals working in the Intensive Indian J Crit Care Med. 2014;18(9):591-5.
[128] Boszczyk BM, Bierschneider M, Panzer S, Panzer W, Harstall R, Schmid K, et al. Fluoroscopic radiation exposure of the kyphoplasty patient. Eur Spine J. 2006;15(3):347-55.
[129] Mroz TE, Yamashita T, Davros WJ, Lieberman IH.J Radiation exposure to the surgeon and the patient during kyphoplasty. Spinal Disord Tech. 2008 ;21(2):96-100.
[130] Fabricant PD, Berkes MB, Dy CJ, Bogner EA. Diagnostic medical imaging radiation exposure and risk of development of solid and hematologic malignancy. Orthopedics. 2012;35 (5):415-20.
[131] Synowitz M1, Kiwit J. Surgeon's radiation exposure during percutaneous vertebroplasty. J Neurosurg Spine. 2006;4(2):106-9.
[132] Goodman BS, Carnel CT, Mallempati S, Agarwal P. Reduction in average fluoroscopic exposure times for interventional spinal procedures through the use of pulsed and low-dose image settings. Am J Phys Med Rehabil. 2011;90(11):908-12.
[133] Boszczyk BM, Bierschneider M, Panzer S, Panzer W, Harstall R, Schmid K, Jaksche H. Fluoroscopic radiation exposure of the kyphoplasty patient Eur Spine J. 2006 ;15(3): 347-55.
[134] Perisinakis K, Damilakis J, Theocharopoulos N, Papadokostakis G, Hadjipavlou A, Gourtsoyiannis N. Patient exposure and associated radiation risks from fluoroscopically guided vertebroplasty or kyphoplasty.Radiology. 2004;232(3):701-7.
[135] Nnational Council on Radiation Protection and Mesurements, 2007. Ionizing Radiation Exposure of the Population of the United States, Report 160, Bethesda, MD. 2009.
[136] Borgström F, Beall DP, Berven S, Boonen S, Christie S, Kallmes DF, Kanis JA, Olafsson G, Singer AJ, Åkesson K. Health economic aspects of vertebral augmentation procedures. Osteoporos Int. 2015;26(4):1239-49.
[137] McCullough BJ, Comstock BA, Deyo RA, Kreuter W, Jarvik JG. Major medical outcomes with spinal augmentation vs conservative therapy. JAMA Intern Med. 2013;173(16):1514-21.
[138] Hillmeier JS, Meeder PJ, Noledge G, Kasperk C. Minimally invasive reduction and stabilization of osteoporotic vertebral body fractures (balloon kyphoplasty). Operat Orthop Traumatol. 2003;15:343-63.
[139] Fisher A. Percutaneous vertebroplasty: a bone cement procedure for spinal pain relief. Ottawa: Canadian Coordinating Office for Health Technology Assessment (CCOHTA) 2002. http://www.ccohta.ca. Last accessed on Jul 2016.
[140] Wong CC, McGirt MJ. Vertebral compression fractures: a review of current management and multimodal therapy. J Multidiscip Healthc. 2013;6:205-14.
[141] Cooper C, Atkinson EJ, Jacobsen SJ, O’Fallon WM, Melton LJ., 3rd Population-based study of survival after osteoporotic fractures. Am J Epidemiol. 1993;137(9):1001-5.
[142] Edidin AA, Ong KL, Lau E, Schmier JK, Kemner JE, Kurtz SM . Cost-effectiveness analysis of treatments for vertebral compression fractures. Appl Health Econ Health Policy. 2012;10(4):273-84.
[143] McGirt MJ, Parker SL, Wolinsky JP, Witham TF, Bydon A, Gokaslan ZL. Vertebroplasty and kyphoplasty for the treatment of vertebral compression fractures: an evidenced-based review of the literature. Spine J. 2009;9(6):501-8.
[144] Klezl Z, Bhangoo N, Phillips J, Swamy G, Calthorpe D, Bommireddy R. Social implications of balloon kyphoplasty: prospective study from a single UK centre. Eur Spine J. 2012;21(9):1880-6.
[145] Borse, MS. Cost utility analysis of balloon kyphoplasty and vertebroplasty in the treatment of vertebral compression fractures in the United States. Theses and Dissertations. 2013.
[146] Vinayak K. Prasad, Adam S. Cifu. Ending Medical Reversal. Johns Hopkins University Press. 2015.
Rib and sternum fractures are an infrequent complication. A systematic review cited 8 studies that reported incidence ranges from 0.6%‒4.3% [81]. Improper patient positioning as well as leaning over the patient’s back during surgery may result in rib fractures [17,103,119]. We experienced a case in which a patient with a successful kyphoplasty procedure who was seriously compromised with severe pain from 4 rib fractures. This complication occurred when pressure was applied over the kyphotic deformity in order to reduce the wedged vertebra.
Infection
Postoperative infection is a rare but devastating complication of kyphoplasty. A few cases have been reported in the literature [120,121]. Ongoing back pain and/or neurologic complication are the predominant presenting symptoms. Staphylococcus aureus is the most common pathogen [122,123]. Tuberculous spondylitis has also been reported [124]. Several studies have claimed that infection after cementoplasty procedure is likely related to a prior systemic infection, an immunocompromised condition, or intraoperative contamination. Preoperative prophylactic antibiotic administration is recommended. Cement mixed with antibiotics has also been recommended in the cases with a previous infection or in immunocompromised patients [125]. In case of concurrent infection, the procedure must be postponed until the infection is controlled. Cementoplasty infection can be treated conservatively with a course of antibiotics based on antibiotic sensitivity testing [126]. Infection refractory to conservative treatment or recurrent infection should be treated with corpectomy, cement removal, and instrumented spinal reconstruction [125].
Radiation Exposure
Long-term low-dose radiation exposure has been associated with leukemia, and thyroid or other cancers [127]. Nonneoplastic effects of radiation include genetic mutation, cataract, and developmental malformation of the fetus [127]. Radiation exposure and associated risks during cement augmentation procedures may be considerable for the patient, the surgeon and the staff; and therefore, actions should be taken to minimize exposure [128]. Mroz et al. reported that during kyphoplasty, the exposure time was 5.7±2.0 minutes/vertebra for a 1-level, 3.9±0.8 minutes/vertebra for a 2-level, and 2.9±1.2 minutes/vertebra for a 3-level kyphoplasty. Surgeon exposure as measured by the protected dosimeter was less than the minimum reportable dose (<0.010 mSv). Exposure as measured by the unprotected dosimeter, which is equivalent to deep whole-body exposure, was 0.248±0.170 mSv/vertebra. Eye exposure was 0.271±0.200 mSv/vertebra, and the shallow exposure (hand/skin) was 0.273±0.200 mSv/vertebra. Hand exposure was 1.744±1.173 mSv/vertebra. Without eye or hand protection, total radiation exposure dose to these areas would exceed the occupational exposure limit after 300 cases per year [129]. Protection of the hands and the eyes of the surgeon by using proper safety equipment, including radiation safety gowns, thyroid shields, gloves, and lead glasses, is strongly recommended [130]. In a similar study, emphasis was given to the importance of surgeons wearing lead glove protection on their leading hands during percutaneous vertebroplasty procedures. This measure has resulted to a 75% reduction rate of exposure to radiation [131].
Measures to minimize radiation exposure during kyphoplasty involve the use of low-dose or pulsed fluoroscopy [132] and the use of simultaneous biplanar fluoroscopy. When an optimal setting has been found, it is continued throughout the procedure and radiation is not "wasted" readjusting to a second plane of view [133]. Patient and staff radiation exposure is closely associated with their distance from the fluoroscopy beam. The source-to-skin distance during the procedure should not be less than 35 cm [134]. Unprotected staff working less than 70 cm from a fluoroscopic beam receive significant amounts of radiation, whereas those working more than 91.4 cm from the beam receive an extremely low amount of radiation [135].
Cost
Cost effectiveness is a contentious issue. The cost effectiveness of vertebral augmentation techniques for OVCFs has been challenged [136,137]. A drawback of balloon kyphoplasty is the high cost of the instrumentation which has been estimated at 3500 euro per treated level, whereas for vertebroplasty the cost is approximately 500 euro per level [138,139]. There is an additional cost and risk of general anesthesia with kyphoplasty, although it can be performed using local anesthesia for 1 or 2 levels. Multiple levels are often under general anesthesia. Studies have not taken into consideration patients with neurologic and musculoskeletal problems associated with OVCFs. Osteoporotic compression fractures have been associated with a 15% higher mortality rate [140,141]. Even for the oldest patients, both procedures are considered to be cost effective in terms of cost per life-year gained [142]. Patients have been found to require primary care services at a rate 14 times greater than the general population in the first year after a symptomatic vertebral fracture [143]. Compared to conservative treatment, significant reduction in mortality and drift in social functionality in patients treated with balloon kyphoplasty was identified at 1-year follow-up in a prospective UK study [144]. A cost-effectiveness analysis of OVCFs treatment among 858,978 patients in the Medicare dataset (2005‒2008) demonstrated kyphoplasty as cost effective and cost saving compared with vertebroplasty [142]. Borse conducted a cost-utility analysis from a payer’s perspective using a Markov model to assess the cost utility of balloon kyphoplasty compared with vertebroplasty. They found that balloon kyphoplasty is associated with better utility and higher effectiveness compared with vertebroplasty [145].CONCLUSIONS
Based on the best available evidence in our review of the literature, it appears that both vertebroplasty and kyphoplasty are valuable procedures in the management of OVCFs. These minimally invasive surgical procedures are not without risk, but potential complications can be minimized. It is imperative to take caution and care with these procedures and identify and promote best practice. In a systematic review [17] analyzing several reports on OVCFs it appears that osteoporosis is not innocuous as it can be complicated with serious neurological deficit and pulmonary and social problems. One third of these patients develop variable degrees of back pain attributed to facet arthropathy, deformity, and pseudoarthrosis. In a recently published book "Ending Medical Reversals", the authors extensively criticized vertebroplasty as ineffective and a harmful medical practice [146]. The majority of studies we reviewed support cementoplasty. A recent RCT [19] exonerates vertebroplasty by demonstrating its superiority over sham procedure and the potentially serious complications of OVCFs [17].
Vertebroplasty is indicated for the uncomplicated OVCF in the first 3 months and appears a more cost-effective procedure. In the early post-fracture period, some reduction of the fracture with postural hyperextension can be accomplished. To minimize cement extravasation, the cement should be of higher viscosity and should be inserted slowly using the kyphoplasty cement bone fillers. Balloon kyphoplasty is indicated in older fractures, when postural reduction is not feasible, and in established pseudoarthrosis. In cases of indeterminate cement interdigitation which may not prevent anterior cement migration and loss of reduction, this procedure can be augmented by a short posterior transpedicular stabilization.
We believe that a well designed randomized controlled trial which includes stratification of patient morbidity metabolic bone activity, and vertebral fracture activity is needed at this point. Patients with OVCFs are likely to have comorbid conditions and the indication for intervention, optimal timing, and manner of cementoplasty is still indeterminate. REFERENCES
[1] Galibert P, Deramond H, Rosat P, Le Gars D. Preliminary note on the treatment of vertebral angioma by percutaneous acrylic vertebroplasty. Neurochirurgie. 1987;33(2):166-8.
[2] Lieberman IH, Dudeney S, Reinhardt MK, Bell G. Initial outcome and efficacy of kyphoplasty in the treatment of painful osteoporotic vertebral compression fractures. Spine. 2001;26(14):1631-8.
[3] Buchbinder R, Osborne RH, Ebeling PR, Wark JD, Mitchell P, Wriedt C, Graves S, Staples MP, Murphy B. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. N Engl J Med. 2009;361(6):557-68.
[4] Kallmes DF, Comstock BA, Heagerty PJ, Turner JA, Wilson DJ, et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med. 2009;361(6):569-79.
[5] American Academy of Orthopaedic Surgeons. The treatment of symptomatic osteoporotic spinal compression fractures guidelines and evidence report. http//www.aaos.org/research/guidelines/SCFguidline.pdf Last accessed 5 November 2016.
[6] Allan S. Brett. Vertebroplasty -1 year later. NEJM Journal Watch Sept 16, 2010.
[7] Noonan P. Randomized vertebroplasty trials: bad news or sham news? AJNR Am J Neuroradiol. 2009;30(10):1808-9.
[8] Smith SJ, Vlahos A, Sewall LE. An objection to the New England Journal of Medicine vertebroplasty articles. Can Assoc Radiol J. 2010;61(2):121-2.
[9] Aebi M. Vertebroplasty: about sense and nonsense of uncontrolled "controlled randomized prospective trials". Eur Spine J. 2009;18(9):1247-8.
[10] Kaufmann TJ, Jensen ME, Schweickert PA, Marx WF, Kallmes DF. Age of fracture and clinical outcomes of percutaneous vertebroplasty. JNR Am J Neuroradiol. 2001;22(10):1860-3.
[11] Ryu KS, Park C The prognostic factors influencing on the therapeutic effect of percutaneous vertebroplasty in treating osteoporotic vertebral compression fractures. J Korean Neurosurg Soc. 2009;45(1):16-23.
[12] Manchikanti L, Singh V, Falco FJ, Cash KA, Pampati V. Lumbar facet joint nerve blocks in managing chronic facet joint pain: one-year follow-up of a randomized, double-blind controlled trial: Clinical Trial NCT00355914. Pain Physician. 2008;11(2):121-32.
[13] Wilson DJ, Owen S, Corkill RA. Facet joint injections as a means of reducing the need for vertebroplasty in insufficiency fractures of the spine. Wilson Eur Radiol. 2011;21(8):1772-8.
[14] Boszczyk B. Volume matters: a review of procedural details of two randomized controlled vertebroplasty trials of 2009. Eur Spine J. 2010;19(11):1837-40.
[15] Nieuwenhuijse MJ, Bollen L, van Erkel AR, Dijkstra PD. Optimal intravertebral cement volume in percutaneous vertebroplasty for painful osteoporotic vertebral compression fractures. Spine (Phila Pa 1976). 2012;37(20):1747-55.
[16] Munk PL, Liu DM, Murphy KP, Baerlocher MO. Effectiveness of vertebroplasty: a recent controversy. Can Assoc Radiol J. 2009;60(4):170-1.
[17] Hadjipavlou AG, Tzermiadianos MN, Katonis PG, Szpalski M. Percutaneous vertebroplasty and balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures and osteolytic tumours. J Bone Joint Surg Br. 2005;87(12):1595-604.
[18] Hadjipavlou AG, Katonis PG, Tzermiadianos MN, Tsoukas GM, Sapkas G. Principles of management of osteometabolic disorders affecting the aging spine. Eur Spine J. 2003;12(Suppl 2):S113-31.
[19] Clark W, Bird P, Gonski P, Diamond TH, Smerdely P, McNeil HP, Schlaphoff G, Bryant C, Barnes E, Gebski V. Safety and efficacy of vertebroplasty for acute painful osteoporotic fractures (VAPOUR): a multicentre, randomized, double-blind, placebo-controlled trial. Lancet. 2016;388(10052):1408-16.
[20] Chen D, An ZQ, Song S, Tang JF, Qin H. Percutaneous vertebroplasty compared with conservative treatment in patients with chronic painful osteoporotic spinal fractures. J Clin Neurosci. 2014;21(3):473-7.
[21] Blasco J, Martinez-Ferrer A, Macho J, San Roman L, Pomés J, Carrasco J, Monegal A, Guañabens N, Peris P. 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 Miner Res. 2012;27(5):1159-66.
[22] Farrokhi MR, Alibai E, Maghami Z. Randomized controlled trial of percutaneous vertebroplasty versus optimal medical management for the relief of pain and disability in acute osteoporotic vertebral compression fractures. J Neurosurg Spine. 2011;14(5):561-9.
[23] Alvarez L, Alcaraz M, Pérez-Higueras A, Granizo JJ, de Miguel I, Rossi RE, Quiñones D. Percutaneous vertebroplasty: functional improvement in patients with osteoporotic compression fractures.Spine (Phila Pa 1976). 2006;31(10):1113-8.
[24] Diamond TH, Bryant C, Browne L, Clark WA. Clinical outcomes after acute osteoporotic vertebral fractures: a 2-year non-randomised trial comparing percutaneous vertebroplasty with conservative therapy. Med J Aust. 2006;184(3):113-7.
[25] Klazen CA, Lohle PN, de Vries J, Jansen FH, Tielbeek AV, Blonk MC, Venmans A, van Rooij WJ, Schoemaker MC, Juttmann JR, Lo TH, Verhaar HJ, van der Graaf Y, van Everdingen KJ, Muller AF, Elgersma OE, Halkema DR, Fransen H, Janssens X, Buskens E, Mali WP. Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomized trial. Lancet. 2010;376(9746):1085-92.
[26] Rousing R, Andersen MO, Jespersen SM, Thomsen K, Lauritsen J. Percutaneous vertebroplasty compared to conservative treatment in patients with painful acute or subacute osteoporotic vertebral fractures: three-month follow-up in a clinical randomized study. Spine (Phila Pa 1976). 2009;34(13):1349-54.
[27] Rousing R, Hansen KL, Andersen MO, Jespersen SM, Thomsen K, Lauritsen JM. Twelve-month follow-up in forty-nine patients with acute/semiacute osteoporotic vertebral fractures treated conservatively or with percutaneous vertebroplasty: a clinical randomized study. Spine (Phila Pa 1976). 2010;35(5):478-82.
[28] Voormolen MH1, Mali WP, Lohle PN, Fransen H, Lampmann LE, van der Graaf Y, Juttmann JR, Jansssens X, Verhaar HJ. Percutaneous vertebroplasty compared with optimal pain medication treatment: short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures. The VERTOS study. AJNR Am J Neuroradiol. 2007;28(3):555-60.
[29] Kroon F, Staples M, Ebeling PR, Wark JD, Osborne RH, Mitchell PJ, Wriedt CH, Buchbinder R Two-year results of a randomized placebo-controlled trial of vertebroplasty for acute osteoporotic vertebral fractures. J Bone Miner Res. 2014;29(6):1346-55.
[30] Comstock BA, Sitlani CM, Jarvik JG, Heagerty PJ, Turner JA, Kallmes DF. Investigational vertebroplasty safety and efficacy trial (INVEST): patient-reported outcomes through 1 year. Radiology. 2013;269(1):224-31.
[31] Yang EZ, Xu JG, Huang GZ, Xiao WZ, Liu XK, Zeng BF, Lian XF. Percutaneous Vertebroplasty Versus Conservative Treatment in Aged Patients With Acute Osteoporotic Vertebral Compression Fractures: A Prospective Randomized Controlled Clinical Study. Spine (Phila Pa 1976). 2016;41(8):653-60.
[32] Wardlaw D, Cummings SR, Van Meirhaeghe J, Bastian L, Tillman JB, Ranstam J, Eastell R, Shabe P, Talmadge K, Boonen S. Efficacy and safety of balloon kyphoplasty compared with non-surgical care for vertebral compression fracture (FREE): a randomised controlled trial. Lancet. 2009;373(9668):1016-24.
[33] Grafe IA, Da Fonseca K, Hillmeier J, Meeder PJ, Libicher M, Nöldge G, Bardenheuer H, Pyerin W, Basler L, Weiss C, Taylor RS, Nawroth P, Kasperk C. Reduction of pain and fracture incidence after kyphoplasty: 1-year outcomes of a prospective controlled trial of patients with primary osteoporosis. Osteoporos Int. 2005;16(12):2005-12.
[34] Kasperk C, Hillmeier J, Nöldge G, Grafe IA, Dafonseca K, Raupp D, Bardenheuer H, Libicher M, Liegibel UM, Sommer U, Hilscher U, Pyerin W, Vetter M, Meinzer HP, Meeder PJ, Taylor RS, Nawroth P. Treatment of painful vertebral fractures by kyphoplasty in patients with primary osteoporosis: a prospective nonrandomized controlled study. J Bone Miner Res. 2005;20(4):604-12.
[35] Kasperk C, Grafe IA, Schmitt S, Nöldge G, Weiss C, Da Fonseca K, Hillmeier J, Libicher M, Sommer U, Rudofsky G, Meeder PJ, Nawroth P. Three-year outcomes after kyphoplasty in patients with osteoporosis with painful vertebral fractures. J Vasc Interv Radiol. 2010;21(5):701-9.
[36] Boonen S, Van Meirhaeghe J, Bastian L, Cummings SR, Ranstam J, Tillman JB, Eastell R, Talmadge K, Wardlaw D. Balloon kyphoplasty for the treatment of acute vertebral compression fractures: 2-year results from a randomized trial. J Bone Miner Res. 2011;26(7):1627-37.
[37] Xie E, Hao DJ, Yang TM, et al. Percutaneous kyphoplasty versus conservative treatment of acute and subacute osteoporotici vertebral compression fractures: a randomized controlled study. Chin J Orthop Trauma. 2011;13:719-24.
[38] Grohs JG, Matzner M, Trieb K, Krepler P. Minimal invasive stabilization of osteoporotic vertebral fractures: a prospective nonrandomized comparison of vertebroplasty and balloon kyphoplasty. J Spinal Disord Tech. 2005;18(3):238-42.
[39] Liu JT, Liao WJ, Tan WC, Lee JK, Liu CH, Chen YH, Lin TB. Balloon kyphoplasty versus vertebroplasty for treatment of osteoporotic vertebral compression fracture: a prospective, comparative, and randomized clinical study. Osteoporos Int. 2010;21(2):359-64.
[40] Lovi A, Teli M, Ortolina A, Costa F, Fornari M, Brayda-Bruno M. Vertebroplasty and kyphoplasty: complementary techniques for the treatment of painful osteoporotic vertebral compression fractures. A prospective non-randomised study on 154 patients. Eur Spine J. 2009;18(Suppl 1):95-101.
[41] De Negri P, Tirri T, Paternoster G, Modano P. Treatment of painful osteoporotic or traumatic vertebral compression fractures by percutaneous vertebral augmentation procedures: a nonrandomized comparison between vertebroplasty and kyphoplasty. Clin J Pain. 2007;23(5):425-30.
[42] Bae H, Shen M, Maurer P, Peppelman W, Beutler W, Li;itz R, Westerlund E, Peppers T, Lieberman I, Kim C, Girardi F. Clinical experience using Cortoss for treating vertebral compression fractures with vertebroplasty and kyphoplasty: 24-month follow-up. Spine (Phila Pa 1976). 2010;35(20):E1030-6.
[43] Kumar K, Nguyen R, Bishop S. A comparative analysis of the results of vertebroplasty and kyphoplasty in osteoporotic vertebral compression fractures. Neurosurgery. 2010;67(Suppl 3):171-88.
[44] Röllinghoff M, Siewe J, Zarghooni K, Sobottke R, Alparslan Y, Eysel P, Delank KS. Effectiveness, security and height restoration on fresh compression fractures—a comparative prospective study of vertebroplasty and kyphoplasty. Minim Invasive Neurosurg. 2009;52(5-6):233-7.
[45] Santiago FR1, Abela AP, Alvarez LG, Osuna RM, García M. Pain and functional outcome after vertebroplasty and kyphoplasty. A comparative study. Eur J Radiol. 2010;75(2):e108-13.
[46] Schofer MD, Efe T, Timmesfeld N, Kortmann HR, Quante M. Comparison of kyphoplasty and vertebroplasty in the treatment of fresh vertebral compression fractures. Arch Orthop Trauma Surg. 2009;129(10):1391-9.
[47] Dohm M, Black CM, Dacre A, Tillman JB, Fueredi G; KAVIAR investigators. A randomized trial comparing balloon kyphoplasty and vertebroplasty for vertebral compression fractures due to osteoporosis. AJNR Am J Neuroradiol. 2014;35(12):2227-36.
[48] Omidi-Kashani F, Samini F, Hasankhani EG, Kachooei AR, Toosi KZ, Golhasani-Keshtan F. Does percutaneous kyphoplasty have better functional outcome than vertebroplasty in single level osteoporotic compression fractures? A comparative prospective study. J Osteoporos. 2013;2013,690329.
[49] Muijs SPJ, Nieuwenhuijse MJ, van Erkel AR, Dijkstra PDS. Percutaneous vertebroplasty for the treatment of osteoporotic vertebral compression fractures: evaluation after 36 months. J Bone Joint Surg Br. 2009;91(3):379-84.
[50] Müller CW, Lange U, van Meirhaeghe J, Wardlaw D, Bastian L, Boonen S, Krettek C. An international multicenter randomized comparison of balloon kyphoplasty and nonsurgical care in patients with acute vertebral body compression fractures Eur Spine J. 2007;16:1977.
[51] Van Meirhaeghe J, Bastian L, Boonen S, Ranstam J, Tillman JB, Wardlaw D; FREE investigators. A randomized trial of balloon kyphoplasty and nonsurgical management for treating acute vertebral compression fractures: vertebral body kyphosis correction and surgical parameters. Spine (Phila Pa 1976). 2013;38(12):971-83.
[52] Kim KH, Kuh SU, Chin DK, Jin BH, Kim KS, Yoon YS, Cho YE. Kyphoplasty versus vertebroplasty: restoration of vertebral body height and correction of kyphotic deformity with special attention to the shape of the fractured vertebrae. J Spinal Disord Tech. 2012;25(6):338–44.
[53] Guo JB, Zhu Y, Chen BL, Xie B, Zhang WY, Yang YJ, Yue YS, Wang XQ. Surgical versus non-surgical treatment for vertebral compression fracture with osteopenia: a systematic review and meta-analysis. PLoS One. 2015;10(5):e0127145.
[54] Yuan WH, Hsu HC, Lai KL. Vertebroplasty and balloon kyphoplasty versus conservative treatment for osteoporotic vertebral compression fractures. A meta-analysis. Medicine (Baltimore). 2016;95(31):e4491.
[55] Papanastassiou ID, Phillips FM, Van Meirhaeghe J, Berenson JR, Andersson GB, Chung G, et al. Comparing effects of kyphoplasty, vertebroplasty, and non-surgical management in a systematic review of randomized and non-randomized controlled studies. Eur Spine J. 2012;21(9):1826-43.
[56] Arciero RA, Leung KY, Pierce JH. Spontaneous unstable burst fracture of the thoracolumbar spine in osteoporosis. a report of two cases. Spine (Phila Pa 1976). 1989;14(1):114-7.
[57] Cook DJ, Guyatt GH, Adachi JD, Clifton J, Griffith LE, Epstein RS, Juniper EF. Quality of life issues in women with vertebral fractures due to osteoporosis. Arthritis Rheum. 1993;36(6):750-6.
[58] Papadokostakis G, Damilakis J, Mantzouranis E, Katonis P, Hadjipavlou A. The effectiveness of calcitonin on chronic back pain and daily activities in postmenopausal women with osteoporosis. Eur Spine J. 2006;15(3):356-62.
[59] Robinson Y, Heyde CE, Försth P, Olerud C. Kyphoplasty in osteoporotic vertebral compression fractures—guidelines and technical considerations. J Orthop Surg Res. 2011;6:43.
[60] Gaitanis IN, Hadjipavlou AG, Katonis PG, Tzermiadianos MN, Pasku DS, Patwardhan AG. Balloon kyphoplasty for the treatment of pathological vertebral compressive fractures. Eur Spine J. 2005;14(3):250-60.
[61] Crandall D, Slaughter D, Hankins PJ, Moore C, Jerman J. Acute versus chronic vertebral compression fractures treated with kyphoplasty: early results. Spine J. 2004;4(4):418-24.
[62] Papanastassiou ID, Filis A, Aghayev K, Kokkalis ZT, Gerochristou MA, Vrionis FD. Adverse prognostic factors and optimal intervention time for kyphoplasty/vertebroplasty in osteoporotic fractures. Biomed Res Int. 2014;2014:925683.
[63] Oh GS, Kim HS, Ju CI, Kim SW, Lee SM, Shin H. Comparison of the results of balloon kyphoplasty performed at different times after injury. J Korean Neurosurg Soc. 2010;47(3):199-202.
[64] Kümmell H. Die rarefizierende Ostitis der Wirbelkörper. Deutsche Med. 1895;21180-1.
[65] Jindal N, Sharma R, Jindal R, Garg SK. Kummell’s disease: literature update and challenges ahead. Hard Tissue. 2013;2(5):45.
[66] Yang H, Pan J, Wang G Benefits from kyphoplasty. A review of osteoporotic vertebral fracture nonunion management. Spine (Phila Pa 1976). 2014;39(26):B4-6.
[67] Osterhouse MD, Kettner NW. Delayed posttraumatic vertebral collapse with intravertebral vacuum cleft. J Manipulative Physiol Ther. 2002;25(4):270-5.
[68] Freedman BA, Heller JG. Kummel disease: a not-so-rare complication of osteoporotic vertebral compression fractures. J Am Board Fam Med. 2009;22(1):75-8.
[69] Tsujio T, Nakamura H, Terai H, Hoshino M, Namikawa T, Matsumura A, et al. Characteristic radiographic or magnetic resonance images of fresh osteoporotic vertebral fractures predicting potential risk for nonunion: a prospective multicenter study. Spine (Phila Pa 1976). 2011;36(15):1229-35.
[70] Young WF, Brown D, Kendler A, Clements D. Delayed post-traumatic osteonecrosis of a vertebral body (Kummell's disease) Acta Orthop Belg. 2002;68(1):13–19.
[71] Nickell LT, Schucany WG, Opatowsky MJ. Kummell disease. Proc (Bayl Univ Med Cent). 2013;26(3):300-1.
[72] Zhang GQ, Gao YZ, Chen SL, Ding S, Gao K, Wang HQ. Comparison of percutaneous vertebroplasty and percutaneous kyphoplasty for the management of Kümmell's disease: A retrospective study. Indian J Orthop. 2015;49(6):577-82.
[73] Yang H, Gan M, Zou J, Mei X, Shen X, Wang G, Chen L. Kyphoplasty for the treatment of Kümmell's disease. Orthopedics. 2010;33(7):479.
[74] Chen L, Dong R, Gu Y, Feng Y. Comparison between Balloon Kyphoplasty and Short Segmental Fixation Combined with Vertebroplasty in the Treatment of Kümmell’s Disease. Retrospective Evaluation. Pain Physician 2015;18;373-81.
[75] Li KC, Wong TU, Kung FC, Li A, Hsieh CH. Staging of Kummel’s disease. J Musculoskeletal Res. 2004;8:43-55.
[76] Mochida J, Toh E, Chiba M, Nishimura K. Treatment of osteoporotic late collapse of a vertebral body of thoracic and lumbar spine. J Spinal Disord. 2001;14(5):393-8.
[77] Chen GD, Lu Q, Wang GL, Zou J, Yang HL, Yang Y, Luo ZP. Percutaneous Kyphoplasty for Kummell’s Disease with Severe Spinal Canal Stenosis Retrospective Study. Pain Physician 2015;18;E1021-8.
[78] Kim P, Kim SW. Balloon Kyphoplasty: An Effective Treatment for Kummell Disease? Korean J Spine. 2016;13(3):102-6.
[79] Hulme PA, Krebs J, Ferguson SJ, Berlemann U: Vertebroplasty and kyphoplasty: a systematic review of 69 clinical studies. Spine. 2006;31:1983-2001.
[80] Phillips FM, Wetzel TF, Lieberman I, Campbell-Hupp M. An in vivo comparison of the potential for extravertebral cement leak after vertebroplasty and kyphoplasty. Spine, 2002;27:2173-9.
[81] Tzermiadianos MN, Zindrick MR, Patwardhan AG, Katonis PG, Hadjipavlou AG. The Safety and Effectiveness of Percutaneous Vertebroplasty and Kyphoplasty in Osteoporotic Fractures and Tumors WSJ. 2007;2(2):64-94
[82] Yeom JS, Kim WJ, Choy WS, Lee CK, Chang BS, Kang JW. Leakage of cement in percutaneous transpedicular vertebroplasty for painful osteoporotic compression fractures. J Bone Joint Surg Br. 2003;85: 83-9.
[83] Katonis P, Hadjipavlou A, Souvatzis X, Tzermiadianos M, Alpantaki K, Simmons JW. Respiratory effects, hemodynamic changes and cement leakage during multilevel cement balloon kyphoplasty. Eur Spine J. 2012;21(9):1860-6.
[84] Dudeney S, Lieberman IH, Reinhardt MK, Hussein M. Kyphoplasty in the treatment of osteolytic vertebral compression fractures as a result of multiple myeloma. J Clin Oncol. 2002;20:2382-7.
[85] Lee B, Lee S, Yoo T. Paraplegia as a complication of percutaneous vertebroplasty with polymethylmethacrylate: a case report. Spine. 2002;27:419-22.
[86] Bohner M, Gasser B, Baroud G, Heini P. Theoretical and experimental model to describe the injection of a polymethylmethacrylate cement into a porous structure. Biomaterials 2003;24:2721-30.
[87] Röder C, Boszczyk B, Perler G, Aghayev E, Külling F, Maestretti G. Cement volume is the most important modifiable predictor for pain relief in BKP: results from SWISS spine, a nationwide registry. Eur Spine J. 2013;22(10):2241-8.
[88] Liebschner MA, Rosenberg WS, Keaveny TM. Effects of bone cement volume and distribution on vertebral stiffness after vertebroplasty. Spine (Phila Pa 1976). 2001;26(14):1547-54.
[89] Greene DL, Isaac R, Neuwirth M, Bitan FD: The eggshell technique for prevention of cement leakage during kyphoplasty. J Spinal Disord Tech. 2007;20:229-32.
[90] Groen RJ, Toit DF, Phillips FM, Hoogland PV, Kuizenga K, Coppes MH, Muller CJ, Grobbelaar M, Mattyssen J. Anatomical and pathological considerations in percutaneous vertebroplasty and kyphoplasty: a reappraisal of the vertebral venous system. Spine (Phila Pa 1976). 2004;29(13):1465-71.
[91] Krueger A, Bliemel C, Zettl R, Ruchholtz S. Management of pulmonary cement embolism after percutaneous vertebroplasty and kyphoplasty: a systematic review of the literature Eur Spine J. 2009;18(9):1257-65.
[92] Krebs J, Aebli N, Goss BG, Wilson K, Williams R, Ferguson SJ. Cardiovascular changes after pulmonary cement embolism: an experimental study in sheep. AJNR Am J Neuroradiol. 2007;28(6):1046-50.
[93] Aebli N, Krebs J, Davis G, Walton M, Williams MJ, Theis JC. Fat embolism and acute hypotension during vertebroplasty: an experimental study in sheep. Spine (Phila Pa 1976). 2002;27(5):460-6.
[94] Krebs J, Aebli N, Goss BG, Sugiyama S, Bardyn T, Boecken I, Leamy PJ, Ferguson SJ.J Cardiovascular changes after pulmonary embolism from injecting calcium phosphate cement. Biomed Mater Res B Appl Biomater. 2007;82(2):526-32.
[95] Aebli N, Krebs J, Schwenke D, Davis G, Theis JC. Pressurization of vertebral bodies during vertebroplasty causes cardiovascular complications: an experimental study in sheep. Spine (Phila Pa 1976). 2003;28(14):1513-20.
[96] Coumans JV, Reinhardt MK, Lieberman IH. Kyphoplasty for vertebral compression fractures: 1-year clinical outcomes from a prospective study. J Neursurg Spine. 2003;99:44-50.
[97] Audat ZA, Alfawareh MD, Darwish FT , Alomari AA. Intracardiac leakage of cement during kyphoplasty and vertebroplasty: a case report. Am J Case Rep. 2016;17:326-30.
[98] Kim MN, Jung JS, Kim SW, Kim YH, Park SM, Shim WJ. A sword-like foreign body lodged in the ventricular septum: A rare complication of percutaneous vertebroplasty. Eur Heart J. 2010;31(8):1006.
[99] Grifka RG, Tapio J, Lee KJ. Transcatheter retrieval of an embolized methylmethacrylate glue fragment adherent to the right atrium using bidirectional snares. Catheter Cardiovasc Interv. 2013;81(4):648-50.
[100] Theron J, Moret J. Spinal phlebography. Lumbar and cervical techniques. Berlin: Springer-Verlag. 1978.
[101] Vogelsang H. Intraosseous spinal venography. Amsterdam: Excerpta Medica. 1970.
[102] Souvatzis X, Alpantaki K, Hadjipavlou A. Re: Tran I, Gerckens U, Remig J, et al. First report of a life-threatening cardiac complication after percutaneous balloon kyphoplasty. Spine (Phila Pa 1976). 2013;38:E316-8. Spine (Phila Pa 1976). 2013;38(19):1709.
[103] Teng MM, Cheng H, Ho DM, Chang CY. Intraspinal leakage of bone cement after vertebroplasty: a report of 3 cases. AJNR Am J Neuroradiol. 2006;27(1):224-9.
[104] Patel AA, Vaccaro AR, Martyak GG, Harrop JS, Albert TJ, Ludwig SC, Youssef JA, Gelb DE, Mathews HH, Chapman JR, Chung EH, Grabowski G, Kuklo TR, Hilibrand AS, Anderson DG. Neurologic deficit following percutaneous vertebral stabilization. Spine (Phila Pa 1976). 200;32(16):1728-34.
[105] Becker S, Meissner J, Tuschel A, Chavanne A, Ogon M. Cement leakage into the posterior spinal canal during balloon kyphoplasty: a case report. J Orthop Surg (Hong Kong). 2007;15(2):222-5.
[106] Cotten A, Dewatre F, Cortet B, Assaker R, Leblond D, Duquesnoy B, Chastanet P, Clarisse J. Percutaneous vertebroplasty for osteolytic metastases and myeloma: effects of the percentage of lesion filling and the leakage of methyl methacrylate at clinical follow-up. Radiology. 1996;200(2):525-30.
[107] Park SY, Modi HN, Suh SW, Hong JY, Noh W, Yang JH. Epidural cement leakage through pedicle violation after balloon kyphoplasty causing paraparesis in osteoporotic vertebral compression fractures: a report of two cases. J Orthop Surg Res. 2010;5:54.
[108] Papaioannou I, Baikousis A, Korovessis P. Calcium Phosphate Cement Leakage during Balloon Kyphoplasty Causing Incomplete Paraplegia: Case Report and Review of the Literature. J Orthop Spine Trauma. 2016;2(3):e8894.
[109] Robinson Y, Tschöke SK, Stahel PF, Kayser R, Heyde CE.P. Complications and safety aspects of kyphoplasty for osteoporotic vertebral fractures: a prospective follow-up study in 102 consecutive patients. Patient Saf Surg. 2008;2:2.
[110] Faloon MJ, Ruoff M, Deshpande C, Hohman D, Dunn C, Beckloff N, Patel DV. Risk factors associated with adjacent and remote-level pathologic vertebral compression fracture following balloon kyphoplasty: 2-year follow-up comparison versus conservative treatment. J Long Term Eff Med Implants. 2015;25(4):313-9.
[111] Berlemann U, Ferguson S. J, Nolte LP, Heini PF, Adjacent vertebral failure after vertebroplasty. J Bone Joint Surg. Br. 202;84(5):748-52.
[112] Lin EP, Ekholm S, Hiwatashi A, Westesson PL. Vertebroplasty: cement leakage into the disc increases the risk of new fracture of adjacent vertebral body. Am J Neuroradiol. 2004;25:175-80.
[113] Yang S, Liu Y, Yang H, Zou J. Risk factors and correlation of secondary adjacent vertebral compression fracture in percutaneous kyphoplasty. Int J Surg. 2016;36(Pt A):138-42.
[114] Jian Wu, Yuehong Guan, Shengli Fan Analysis of risk factors of secondary adjacent vertebral fracture after percutaneous kyphoplasty. Biomedical Research 2017;28 (5):1956-61.
[115] Harrop JS, Prpa B, Reinhardt MK, Lieberman I. Primary and secondary osteoporosis' incidence of subsequent vertebral compression fractures after kyphoplasty. Spine (Phila Pa 1976). 2004;29(19):2120-5.
[116] Mukherjee S, Lee Y-P. Current Concepts in the Management of Vertebral Compression Fractures. Operative Techniques in Orthopaedics. 2011;21(3):251-60.
[117] Gaitanis IN, Carandang G, Phillips FM, Magovern B, Ghanayem AJ, Voro; LI, Havey RM, Zindrick MR, Hadjipavlou AG, Patwardhan AG. Restoring geometric and loading alignment of the thoracic spine with a vertebral compression fracture: effects of balloon (bone tamp) inflation and spinal extension. Spine J. 2005;5(1):45-54.
[118] Zhang H, Xu C, Zhang T, Gao Z, Zhang T. Does percutaneous vertebroplasty or balloon kyphoplasty for osteoporotic vertebral compression fractures increase the incidence of new vertebral fractures? A meta-analysis. Pain Physician. 2017;20(1):E13-28.
[119] Layton KF, Thielen KR, Koch CA, Luetmer PH, Lane JI, Wald JT, Kallmes DF. Vertebroplasty, first 1000 levels of a single center: evaluation of the outcomes and complications. AJNR Am J Neuroradiol. 2007;28(4):683-9.
[120] Yu SW, Chen WJ, Lin WC, Chen YJ, Tu YK. Serious pyogenic spondylitis following vertebroplasty: a case report. Spine (Phila Pa 1976). 2004;29(10):E209-21.
[121] Vats HS, McKiernan FE. Infected vertebroplasty: case report and review of literature. Spine (Phila Pa 1976). 2006;31(22):E859-62.
[122] Kallmes DF, Schweickert PA, Marx WF, Jensen ME. Vertebroplasty in the mid- and upper thoracic spine. AJNR Am J Neuroradiol. 2002;23(7):1117-20.
[123] Abdelrahman H, Siam AE, Shawky A, Ezzati A, Boehm H. Infection after vertebroplasty or kyphoplasty. A series of nine cases and review of literature. Spine J. 2013;13(12):1809-17.
[124] Kim HJ, Shin DA, Cho KG, Chung SS. Late onset tuberculous spondylitis following kyphoplasty: a case report and review of the literature. Korean J Spine. 2012;9(1):28-31.
[125] Ha KY, MD, Kim KW, Kim YH, MD, Oh IS, Park SW. Revision surgery after vertebroplasty or kyphoplasty. Clin Orthop Surg. 2010;2(4):203-8.
[126] Schmid KE, Boszczyk BM, Bierschneider M, Zarfl A, Robert B, Jaksche H. Spondylitis following vertebroplasty: a case report. Eur Spine J. 2005;14(9):895-9.
[127] Siddiqui SS, Jha A, Konar N, Ranganathan P, Deshpande DD, Divatia JV. Radiation exposure among medical professionals working in the Intensive Indian J Crit Care Med. 2014;18(9):591-5.
[128] Boszczyk BM, Bierschneider M, Panzer S, Panzer W, Harstall R, Schmid K, et al. Fluoroscopic radiation exposure of the kyphoplasty patient. Eur Spine J. 2006;15(3):347-55.
[129] Mroz TE, Yamashita T, Davros WJ, Lieberman IH.J Radiation exposure to the surgeon and the patient during kyphoplasty. Spinal Disord Tech. 2008 ;21(2):96-100.
[130] Fabricant PD, Berkes MB, Dy CJ, Bogner EA. Diagnostic medical imaging radiation exposure and risk of development of solid and hematologic malignancy. Orthopedics. 2012;35 (5):415-20.
[131] Synowitz M1, Kiwit J. Surgeon's radiation exposure during percutaneous vertebroplasty. J Neurosurg Spine. 2006;4(2):106-9.
[132] Goodman BS, Carnel CT, Mallempati S, Agarwal P. Reduction in average fluoroscopic exposure times for interventional spinal procedures through the use of pulsed and low-dose image settings. Am J Phys Med Rehabil. 2011;90(11):908-12.
[133] Boszczyk BM, Bierschneider M, Panzer S, Panzer W, Harstall R, Schmid K, Jaksche H. Fluoroscopic radiation exposure of the kyphoplasty patient Eur Spine J. 2006 ;15(3): 347-55.
[134] Perisinakis K, Damilakis J, Theocharopoulos N, Papadokostakis G, Hadjipavlou A, Gourtsoyiannis N. Patient exposure and associated radiation risks from fluoroscopically guided vertebroplasty or kyphoplasty.Radiology. 2004;232(3):701-7.
[135] Nnational Council on Radiation Protection and Mesurements, 2007. Ionizing Radiation Exposure of the Population of the United States, Report 160, Bethesda, MD. 2009.
[136] Borgström F, Beall DP, Berven S, Boonen S, Christie S, Kallmes DF, Kanis JA, Olafsson G, Singer AJ, Åkesson K. Health economic aspects of vertebral augmentation procedures. Osteoporos Int. 2015;26(4):1239-49.
[137] McCullough BJ, Comstock BA, Deyo RA, Kreuter W, Jarvik JG. Major medical outcomes with spinal augmentation vs conservative therapy. JAMA Intern Med. 2013;173(16):1514-21.
[138] Hillmeier JS, Meeder PJ, Noledge G, Kasperk C. Minimally invasive reduction and stabilization of osteoporotic vertebral body fractures (balloon kyphoplasty). Operat Orthop Traumatol. 2003;15:343-63.
[139] Fisher A. Percutaneous vertebroplasty: a bone cement procedure for spinal pain relief. Ottawa: Canadian Coordinating Office for Health Technology Assessment (CCOHTA) 2002. http://www.ccohta.ca. Last accessed on Jul 2016.
[140] Wong CC, McGirt MJ. Vertebral compression fractures: a review of current management and multimodal therapy. J Multidiscip Healthc. 2013;6:205-14.
[141] Cooper C, Atkinson EJ, Jacobsen SJ, O’Fallon WM, Melton LJ., 3rd Population-based study of survival after osteoporotic fractures. Am J Epidemiol. 1993;137(9):1001-5.
[142] Edidin AA, Ong KL, Lau E, Schmier JK, Kemner JE, Kurtz SM . Cost-effectiveness analysis of treatments for vertebral compression fractures. Appl Health Econ Health Policy. 2012;10(4):273-84.
[143] McGirt MJ, Parker SL, Wolinsky JP, Witham TF, Bydon A, Gokaslan ZL. Vertebroplasty and kyphoplasty for the treatment of vertebral compression fractures: an evidenced-based review of the literature. Spine J. 2009;9(6):501-8.
[144] Klezl Z, Bhangoo N, Phillips J, Swamy G, Calthorpe D, Bommireddy R. Social implications of balloon kyphoplasty: prospective study from a single UK centre. Eur Spine J. 2012;21(9):1880-6.
[145] Borse, MS. Cost utility analysis of balloon kyphoplasty and vertebroplasty in the treatment of vertebral compression fractures in the United States. Theses and Dissertations. 2013.
[146] Vinayak K. Prasad, Adam S. Cifu. Ending Medical Reversal. Johns Hopkins University Press. 2015.