Bone cements are usually supplied as two component systems, including a liquid and a powder. The powder primary consists of bead-shaped particles that are approximately 40 μm in diameter. These particles contain, in addition to methylmethacrylate copolymers, benzoyl peroxide BPO (the so-called initiator), and zirconium or barium to provide radio-opacity . The second component of bone cement, the liquid, mainly contains the monomers. When the two components are mixed, polymerization is initiated, and self-curing occurs. At room temperature, monomer polymerization can be activated only in the presence of free radicals . These radicals are produced during the reaction of the initiator, BPO, which is contained in the powder. Polymerization is an exothermic reaction, which means that it produces heat and is adversely affected by the application of heat [19, 20]. Core temperatures of 77.3°C have been measured in the center of bone cement in an in vitro vertebroplasty study . This temperature is above the coagulation temperature of proteins. Once polymerization ends, the temperature decreases and the cement becomes solid.
The phases of bone cement
The handling of bone cement can be described by four different phases, based on the corresponding viscosities . The first phase is the mixing phase (up to 1 min), which is the period required to thoroughly homogenize the powder and the liquid. The powder and the liquid can be mixed manually using a bowl and a spatula. Second, the waiting phase (up to several minutes, depending on the type of cement and the handling temperature) is the period required for the cement to reach a non-sticky state. Third, the working phase (2–4 min, depending on the type of cement and the handling temperature) is the period in which the cement is injected. Lastly, the hardening phase is a short period in which the final setting process occurs and polymerization heat develops. In this study, the liquid time is assumed to coincide with the duration of the waiting phase. The hardening phase is difficult to define in clinical situations; thus, the paste time is considered the duration of the working phase together with the hardening phase. Because the hardening phase is short, the paste time roughly corresponds to the working time.
An early injection in the liquid phase may result in bone cement extravasation into the venous system as well as its distant migration to the lungs [10, 21]. If paravertebral vein filling is observed by fluoroscopy, the cement injection should be stopped and staged. Cement viscosity must also be sufficiently high to withstand the blood pressure. If blood mixes with the cement, its strength is reduced. However, a late injection of high viscosity bone cement may result in poor interfaces between the cement and the bone. Additionally, it is difficult to inject the cement through the cannula or spinal needles when it is approaching the final hardening stage.
Cement polymerization is an exothermic reaction . The Arrhenius equation illustrates the exponential effect of temperature on the reaction . In short, the Arrhenius equation gives “the dependence of the rate constant k of chemical reactions on the temperature T (in absolute temperature or kelvins) and activation energy Ea,” as shown below:
By lowering the temperature T, a decreased rate constant k can be expected. Thus, the polymerization time can be increased by lowering the temperature. The instructive package inserts in the commercially available products provide graphic information on the duration of each period with relation to temperature, which indicate that the working time is approximately 2–4 min, depending on the type of cement and the handling temperature. In this study, precooling (i.e., lowering the initial temperature) and ice bath cooling (i.e., lowering the surrounding temperature) prolonged the handling time to 15.2 min and to 112.5 min, respectively. Cooling the mixture is an important method of increasing the duration of injectability. As newer cements are developed, we believe that this general principle will remain the same.
It is convenient to store the cement used for percutaneous vertebroplasty in a refrigerator before mixing to prolong the liquid and the paste times. In the current study, storing the PMMA (liquid ampoule and power packet) and the mixing and injection devices (plastic beaker, spatula, and syringe) in the refrigerator was found to effectively increase the liquid time and the paste time. Our experiment yielded a 1.9-fold increase in the liquid time, a 1.7-fold increase in the paste time and a 1.8-fold increase in the handling time, compared with the polymerization at room temperature. Refrigeration provides a convenient and accessible cooling method if ice is not readily available. Initially, the cement will be overly runny, and the clinician must assess its viscosity before further delivering it. By delaying delivery for a short time, the viscosity will increase until the cement reaches an adequate consistency. With refrigeration, more time will be available to monitor the process of cement distribution within the vertebrae. The procedure can be performed in a controlled manner without any added pressure due to time, and theoretically the possibility of cement leakage will be reduced [12, 15].
Ice bath method
After mixing the bone cement and filling the syringe at room temperature, the device was stored in ice water. The syringes were removed for a short period at 5-min intervals to assess the bone cement injectability. The liquid time and paste time increased dramatically, and we observed a substantial retardation of the polymerization process . It has been recognized that placing a cement mixture in an ice bath has a significant influence on the cement polymerization time . Chavali et al.  qualitatively investigated the extension of the polymerization time of bone cement with ice bath cooling. They concluded that the injectability of a PMMA mixture could be improved by cooling it in an iced bath. However, Chavali’s study only gave a qualitative description, without any quantitative data and statistical analysis. In the present study, not only the liquid, paste, and handling times were compared among three groups, the mechanism of extending polymerization time was also illustrated by Arrhenius equations. Our results indicated that even though the handling time increased by precooling method was less than ice bath cooling, precooling method is easier for application. Surgeons can choose either method according to different clinical needs.
Our experiment yielded a 16.5-fold increase in the liquid time, an 8.4-fold increase in the paste time and a 13.2-fold increase in handling time compared with the polymerization at room temperature. Long liquid times (or waiting times) allow the cement to be injected at a fairly constant consistency with one preparation, even when multiple spinal levels need vertebroplasty. In our previous study, the average amount of bone cement needed per vertebra was 4-6 mL [23, 24]. The amount of bone cement made in each preparation could fill up two 10 ml syringes. By simultaneously submerging the two syringes in ice water, a clinician could successfully inject up to four vertebrae.
Simple and decreases costs
The question of whether temperature alterations change the biomechanical properties of bone cement remains controversial [25–27]. Lewis  assessed the influence of the storage temperature of the unmixed cement constituents (21°C vs. 4°C) on the fatigue performance. They concluded that the storage temperature does not exert a significant influence on the fatigue performance of the bone cement. However, Vallo’s study  demostrated that decreasing the external temperature of bone cement will decrease the peak curing temperature, which will increase the amount of residual monomer present in the cement. This remaining unreacted monomer acts as a plasticizer, softening the cement. Additionally, some of the current clinical and biomechanical data suggest that vertebroplasty can cause the development of adjacent vertebral fractures shortly after augmentation [28, 29]. These findings have been attributed to high Young’s moduli of PMMA bone cements compared to that of the osteoporotic cancellous bone. Although cooling the exterior of the cement might reduce its mechanical properties, this concern should not influence the method’s application in vertebroplasty because the gap between the mechanical strength of the bone cement and that of the osteoporotic cancellous bone is very large.
Some clinicians have routinely used temperature reduction methods in percutaneous vertebroplasty and have found no adverse side effects [8, 15]. The increased handling time allows the clinician to leave the cement, which has filled the leak side or the paravertebral vein, to act as a plug before continuing the injection. The increased handling time provides the clinician with time to discern how the bone cement is filling the vertebral body. Cooling, especially the ice bath technique, is also a good method for training allowing multiple injections into different vertebrae from one preparation.
This report has some limitations. We only studied the effects of temperature reduction on one type of cement. There are many types of bone cement with different chemical and physical properties. Additionally, some clinicians prefer to use 1 mL syringes or plungers for cement injection instead of the 10 mL standard Luer-Loc syringes. The injectability of bone cement varies among different brands and devices. Surgeons who want to apply these hypothermic techniques have to set up their own protocols.