Filling Materials Used in Kyphoplasty and Vertebroplasty for Vertebral Compression Fracture: A Literature Review

Abstract

Kyphoplasty (KP) and vertebroplasty (VP) are both minimally invasive surgical techniques, which can enhance the mechanical stability of the vertebral lesion by injecting filling materials into the fractured vertebra. The filling materials used in KP and VP include injectable PMMA, composite bone cement, biodegradable bone cement, calcium phosphate cement (CPC), and others. Different filling materials have different effects on the biomechanical properties of vertebral bodies, causing various biomechanical effects on the adjacent vertebral bodies. In conclusion, the development of filling materials can improve the anti-pressure capacity and effectively maintain good morphological characteristics of fractured vertebral bodies.

Keywords::

• vertebral compression fracture
• kyphoplasty
• vertebroplasty
• filling materials
• biomechanics

Abbreviations
BMP	=	bone morphogenetic protein
CPC	=	calcium phosphate cement
HA	=	hydroxyapatite
KP	=	kyphoplasty
MMA	=	methylmethacrylate
PMMA	=	Polymethyl methacrylate
SrHAC	=	strontiumcontaining hydroxyapatite cement
VCF	=	vertebral compression fracture
VP	=	vertebroplasty

INTRODUCTION

Vertebral compression fracture (VCF) is the most common complication in patients with osteoporosis. The 5-year mortality rate in patients with serious VCF is up to 23–34% after conservative treatment. At present, the most commonly used surgical treatments include simple bone graft fixation with open vertebral body, and fixation with rigid internal fixation materials, both of which have various surgical trauma and complications. Percutaneous vertebroplasty (VP) has been used to treat osteoporotic vertebral body compression fractures with effective results [1,2]. Kyphoplasty (KP) is a new, minimally invasive surgical technique, which can enhance the mechanical stability of the vertebral lesion by injecting filling materials into the fractured vertebra after balloon expansion. In clinical use, KP and VP have stable and reliable therapeutic effects [3–5]. However, there are still some complications and issues surrounding KP and VP application, and for long-term clinical follow-up [6–8]. Thus, it is important to continue to improve the technology of the filling materials used in KP in order to evolve the biomechanical characteristics of the postoperative vertebra, and to reduce the incidence of complications.

METHODS

The Medline database was searched in October 2009 using the keywords “vertebral compression fracture,” “vertebroplasty,” “kyphoplasty,” “balloon kyphoplasty,” “percutaneous kyphoplasty,” “percutaneous vertebroplasty,” “filling materials,” “bone cement,” “biomechanics,” “surgery,” “treatment,” “reconstruction,” “leakage,” “complications,” and combinations of these words. The “What's New” Medline function was applied to the above-described search strategy to update the list of articles during the time of manuscript preparation. Two readers studied full texts of relevant English language articles (review articles included) and their reference lists in order to search for additional relevant articles. This traditional approach is more prone to bias than a meta-analysis or systematic review. However, we endeavored to unreservedly include all studies. Many valuable studies would have been excluded if a very strict inclusion criterion were applied.

Quality Assessment

In order to assess quality of the reviewed studies, studies were assessed not only by their overall methodology, but also by the results with specific filling materials.

RESULTS

Polymethylmethacrylate

Polymethyl methacrylate (PMMA) is the synthetic polymer of methyl methacrylate. This material was developed in 1928 in various laboratories and was brought to market in 1933 by the German company Rohm and Haas (GmbH & Co. KG). PMMA was proven to be useful, as in one reported session when at least four injections were able to successfully achieve the prophylactic reinforcement of adjacent vertebrae as well. The use of a low-viscosity PMMA in combination with a non-ionic liquid contrast dye provides a reliable and safe procedure [9,10]. At present, PMMA is still the most commonly used filling material in KP and VP due to the following advantages: low viscosity, easy to perfuse, sufficient ability to strengthen and stiffen vertebral body quickly, and relatively cheaper price. However, there are still the following limitations:

(1) Low viscosity—a common leakage complication—can lead to a serious condition that would compress the spinal cord, possibly causing a pulmonary embolism to enter the blood vessels through venous return, leading to death.

(2) Exothermic reaction: PMMA exothermic reaction can cause thermal burns to the surrounding tissue; some studies have shown that such reaction temperatures could reach 39–112°C in front of the vertebral body, up to 49–112°C in the vertebral body center, and 39–57°C at the spinal canal, with the temperature over 50°C delayed for 5, 8 and 25 min, respectively [11].

(3) Due to lack of conductivity and bioactivity, PMMA could not be degraded, resulting in the loss of interface between cement and bone.

(4) After injection, differences in mechanical strength between PMMA and the adjacent vertebral body can easily lead to adjacent vertebral fractures.

(5) The release of toxic monomers and PMMA debris suppresses the cell growth, DNA synthesis, and glucose metabolism, and thus exerting cytotoxic effects. This monomer toxicity can cause a sudden drop in blood pressure, and lead to sudden death in patients. Moreover, allergens, decreased local anti-infection capacity, tumorgenesis, and other adverse reactions existed. However, some studies have reported pulmonary embolism after PMMA was injected [12,13]. In order to improve its mechanical properties and biocompatibility, some studies have added inorganic particles or a fiber-reinforced polymer binder into PMMA in order to improve its biological activity. However, the results are still unsatisfactory due to an even faster decrease in mechanical strength.

Composite Bone Cement

Orthocomp, cortoss, hydroxyapatite composite resin (Kuraray) have properties similar to PMMA, but they have additional benefits such as appropriate viscosity, non-transmission of X-ray, a rapid hardening process, low heat production, better mechanical properties, biological activity, bone induction abilities, and many others. Cortoss is a novel synthetic bone cavity filling material that is easy to diffuse into the cancellous bone and is a model similarly elastic to bone. Orthocomp is an enhanced variety of glass-ceramic matrix composite bone cement; it is not absorbent, but this variety of cement can combine with cancellous bone through chemical bonds. Jasper et al. [14] found that the strength and stiffness of Orthocomp was as much as double that of PMMA bone cement. Orthocomp also has a better recovery of vertebral strength and stiffness. Lu et al. [15] introduced a composite bone cement made with strontium-containing hydroxyapatite powder and BisGMA (bisphenol A diglycidylether dimethacrylate). They performed about 30,000 and 20,000 times of fatigue load test in an animal experimental model, and found that the vertebral body rigidity decreased by 75% and 56%, compared with the control group, with an average compressive strength load limit of 5,056 N and 5,301 N, respectively.

Calcium Phosphate Cement

Calcium phosphate cement (CPC) has characteristics such as arbitrary shaping, self-setting, and gradual degradation, all of which are better than PMMA in terms of biocompatibility, bone conductivity, and viscosity [16]. The replacement of new bone is gradually advanced from the surface to the depth of CPC; mean depth in 6 m is 6 mm, and in 12 m is 114 mm. CPC may be a better filling material for KP, while in vivo and long-term biomechanical and biological effects require further study [17]. Lim and Heini et al. [17,18] suggested that heat production decreases significantly during the CPC and modified CPC forming process, with excellent dispersion capability, and can markedly enhance osteoporotic vertebral compressive strength and stiffness. The stiffness of CPC is between the normal vertebral body and vertebral body with osteoporosis. After surgery, this can reduce the upper and lower vertebral fracture risk due to changes in vertebral body stiffness[19]. CPC has a porous structure after hardening, which can induce bone formation but not osteogenesis. Bioactivated CPC, with a moderate hardening feature, combines with bone morphogenetic protein (BMP) to accelerate the degradation of CPC and osteogenesis. However, Heini et al. [20] suggested that the CPC biodegradation could lead to a corresponding problem. The rapid absorption of bone cement will weaken the vertebral body and cause further collapse during treatment of osteoporotic vertebral compression fractures.

Cunin applied BMP into a natural coral with porous structure and suggested that granular natural coral is injectable, biocompatible, and has bone-inductivity, though its biomechanical properties require further study to prove [18]. Some studies report that the methylmethacrylate (MMA) treated strontium-containing hydroxyapatite cement (SrHAC) has had very good recovery results in vertebral body stiffness, compression strength, bending strength, and Young's modulus [21].

DISCUSSION

There have been some studies on the height restoration and biomechanical changes of vertebral body after KP and VP [22–24]. Garfin et al. reported a clinical study that was completed in a number of hospitals from October 1998 to May 2000. In this study of 340 cases and involving 603 vertebrae, with the longest follow-up at over 18 m, more than 90% of the patients experienced an improvement of their symptoms. A 5-year follow-up on 13 cases indicated better clinical outcomes, with higher visual analogue scale (VAS) scores, but with VAS scores still significantly lower than their preoperative levels. No further molding vertebral compression was observed [8]. PMMA or calcium phosphate biomechanics studies confirmed the stability of fractures after VP significantly increased [25], which could prevent further vertebral collapse and deformation. VCF reduced the motive segment of the vertebral body's compressive strength, which increased the load on the posterior column, resulting in pain. The measure on corpse suggested that the pressure load on the lesion of the posterior vertebral column increased 21–42% at flexion state, and 39–68% at extension state. After KP, the same load decreased 26% and 61%, respectively, suggesting that no significant difference existed before and after operation. Reversing the pressure load on the posterior structure immediately gave relief from pain [26].

The idea that more bone cement can enhance the vertebral body's stiffness drives some clinicians to inject the maximum dose of cement into the vertebral body lesion in an attempt to improve its vertebral compressive strength. It has been reported that nearly 70% of the vertebral body volume was injected with bone cement [27]. Higher vertebral body strength puts greater stress on the upper and lower vertebral bodies, increasing the incidence of vertebral fracture, especially in elderly patients with severe osteoporosis. After KP, the adjacent vertebral bodies have decreased anti-compression force and intervertebral displacement; severity of these effects is related to the amount of bone cement used [25,28]. Therefore, the challenge of how to improve the strength of vertebral bodies has been a topic of great scientific research [29] Molloy et al. injected about 2-8 ml of bone cement into 120 vertebral bodies (T6-L5), and found that the amount of injected cement had little relationship with the anti-compression strength and stiffness of vertebral bodies (r2, 021, and 027, respectively). The recovery of compressive strength and stiffness only requires an injection of, on average, 16.2% and 29.8% of the vertebral body volume [30]. The greater the amount of injected bone cement, the higher the chance of leakage [31–33]. Some studies have shown that the recovery of vertebral stiffness after KP was related to the amount of cement injected. These studies showed that 14% of volume with bone cement could meet the stiffness requirements, and 30% of volume would increase the stiffness significantly. This creates the correlation between higher volumes of cement and higher risk of adjacent vertebral body fractures [34]. Different filling materials have different effects on the biomechanical properties of vertebral bodies after KP. Belkoff et al. investigated the effects on the biomechanical properties of vertebral bodies after filling with Simplex P, Cranoplastic, Osteobond, and Orthocomp, respectively. The results suggested that Simplex P, Osteobond, and Orthocomp could effectively restore vertebral body stiffness and compressive strength, while the Cranoplastic only increased the compression strength, and the degree of stiffness recovery using Orthocomp was better than with Simplex P [35,36]. Novel materials like CPC could recover the anti-compression strength in vertebral body with osteoporosis, and provide good recovery of stiffness. CPC's porous structure allows ingrowth of new bone to increase its biocompatibility. While hydroxyapatite (HA) bone cement had a good recovery effect on anti-compression strength, it had limited ability to restore stiffness. MMA treated SrHAC not only facilitated interface integration, but also improved the vertebral body stiffness, compression strength, bending strength, and Young's modulus, all at levels superior to SrHAC [21].

The filling materials had significant impact on the adjacent vertebral bodies, especially on the upper and lower bodies [37]. The purpose of KP is to recover compressed vertebral body stiffness and compressive strength to the greatest extent possible, but this quest might be an important reason behind fractures of adjacent vertebral bodies due to increased pressure on these vertebral bodies [36]. Berlemann et al. [25] investigated fresh specimens of 10 cases, including 20 pairs of adjacent vertebral bodies, and randomly divided them into two groups. In one group, they filled the lower vertebral body with PMMA, and used the other group as a control. The biomechanical study on the upper vertebral body load showed that no significant difference existed between the two groups in the upper vertebral bodies when under limited loads. However, the load pressures in the experimental group were 19% lower than the control group, and the fractures all occurred on the upper vertebral body in the experimental group. There have been reports of upper and lower adjacent vertebral body fracture after KP. Perez Higueras et al. [8] investigated 13 cases after KP during a 5-year, long-term follow-up and observed 2 cases of vertebral fractures in adjacent vertebral bodies. A survey on a group of elderly patients (mean: 74 years old) after KP showed that the probability of adjacent vertebral fractures increased 6.6% annually. When the lower vertebral body or more vertebral bodies was affected, the 1-year fracture risk would increase 5 times that of normal, and the probability of a new fracture was about 19.2% [38]. VCF might be in correlation with the increased intensity of the adjacent vertebral body. In L4/5 vertebral body, it was found that hard bone cement caused about 7% compression on the endplate of a superior vertebral body after VP, increasing intradiscal pressure by 19%. When the spinal load increased, the activity of the intervertebral joint decreased 11%, the inner protrusion of the inferior endplate of the superior vertebral body increased 17%, both of which might be the causative factors behind adjacent vertebral fractures after angioplasty [39]. In order to alleviate postoperative pain, the patients changed their lifestyle. However, the inclusion of spinal exercises led to increased load pressure, which then led to increased odds of vertebral fractures [40]. Meanwhile, the increased intervertebral disc pressure of the adjacent vertebral body also raised the risk of intervertebral disc herniation after angioplasty.

The application of different materials causes various biomechanical effects on the adjacent vertebral bodies. In general, the elastic modulus of cancellous bone is 168 MPa, while PMMA is 2700 MPa, and CPC is about 180 MPa. CPC is more effective at avoiding the stress shielding effect, abnormal load transfer, as well as reducing secondary fracture of adjacent vertebral bodies. Studies have shown that after vertebroplasty with CPC, there was no significant change in stress to the adjacent discs, and minimal stress shielding and abnormal load transfer effects. Compared to PMMA and KP, CPC has shown a potential advantage in reducing the incidence of adjacent vertebral fractures. To date, there is still no completely randomized trial on the compared risks of adjacent vertebral fractures with and without vertebroplasty. However, adjacent vertebral fractures may be a natural process in severe osteoporosis, especially in adjacent vertebral bodies that have similar mechanical and morphological characteristics.

CONCLUSION

Currently, the filling materials used in KP include injectable PMMA, composite bone cement such as a glass-ceramic-reinforced composite (Orthocomp), Cortoss (Orthovia), hydroxyapatite composite resin (Kuraray) as well as biodegradable bone cement such as substitute material from natural coral bone (CPC). The development of filling materials can enhance the anti-pressure capacity, effectively maintain good morphological characteristics of fractured vertebral bodies, and may restore the biomechanical properties of fractured vertebral bodies to their best state.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.