Properties of Bone Cement: What Is Bone Cement?

3.1

Properties of Bone Cement: What is Bone Cement?

Klaus-Dieter Kühn

Summary > Note: Historical Development 1901 Thesis of Otto Röhm »Polymerization prod- Bone cements based on polymethylmethacrylate are ucts of acrylic acid« essential products in joint arthroplasty. Originally devel- 1928 Röhm and Haas patented application of oped for dental applications, they have been used success- PMMA as plastic material fully in arthroplasty surgery for more than 40 years. 1936 Kulzer patented heat-curable dough Though they seem to be simple cold curing pow- 1943 Kulzer and Degussa patented a cold-curing der/liquid systems, there are many details in which bone material cements can differ leading to significantly varying prop- 1958 Sir John Charnley succeeded in anchoring erties. femoral head prostheses with self-curing cement = bone cement on acrylic basis

Acrylic Bone Cements – Bone Cements Based When chemists discovered that the polymerization of on Polymethylmethacrylate MMA would occur by itself at room temperature if a co-initiator is added, the companies Degussa and Kulzer History (1943, patent DRP 973 590) by using tertiary aromatic amines established a protocol for the chemical production Polymethylmethacrylate (= PMMA) was known in 1902 of PMMA bone cements in 1943; this process is still valid by the chemist Otto Röhm. As »Plexiglas«, a glass-like to this day. These studies must be considered the hour of hard material, it has been used for many purposes since birth of PMMA bone cements. then. By 1936, the company Kulzer (1936; patent DRP Judet and Judet [6] were the first to introduce an 737058) had already found that a dough can be produced arthroplastic surgical method. Soon, however, it became by mixing ground polymethylmethacrylate (PMMA) apparent that the PMMA (Plexiglas) prosthesis used could powder and a liquid monomer that hardens when benzoyl not be integrated in the body (for biological and mechani- peroxide (BPO) is added and the mixture is heated to 100 cal reasons). In 1958, Sir John Charnley first succeeded °C in a stone mould. The first clinical use of these PMMA in anchoring femoral head prostheses in the femur with mixtures was an attempt to close cranial defects in mon- auto-polymerizing PMMA [2]. Charnley called the mate- keys in 1938. When these experiences became known, rial »bone cement on acrylic basis». His studies described surgeons were anxious to try these materials in plastic a totally new surgical technique [3]. surgery on humans. The heat curing polymer Paladon 65 PMMA bone cements originally were only cold- was soon used for closing cranial defects in humans by polymerized materials based on methyl methacrylate, producing plates in the laboratory and later adjusting the whereas for some years the term has been used for bone hardened material on the spot [7]. substitute materials, too, hoping to substitute the biologically inert polymethylmethacrylate by biologically active materials. 53 3 Chapter 3.1 · Properties of Bone Cement: What is Bone Cement?

Clinical Use and Function

Bone cements are used for the fixation of artificial joints. The cements fill the free space between the prosthesis and the bone and constitute a very important zone. Owing to their optimal rigidity, the cements can evenly buffer the forces acting against the bone. The close connection between the cement and the bone as well as cement and the prosthesis leads to an optimal distribution of the stresses and interface strain energy. The transfer of the forces bone-to-implant and implant- to-bone is the primary task of the bone cement. The ability to do so reliably for a long time is crucial for the long-term ⊡ Fig. 3.1. Methyl methacrylate survival of the implant. An adequate cement interdigita- tion/interlock and reinforcement of the spongious bone are of utmost importance. If the continuous stress from out- side exceeds the capability of the bone cement to transfer and absorb forces, a fatigue break is possible [8]. Antibiotic-loaded bone cements are also drug-deliv- ery systems. It is well known that artificial implants are especially susceptible to bacterial colonisation on their surfaces because the germs can then escape the natural protection via the body and cause a periprosthetic infec- tion. When applying antibiotics locally, bone cements can have the function of the carrier matrix. > Note: Functions of Bone Cements ⊡ Fig. 3.2. Poly(methyl methacrylate) ▬ Fixation of artificial joints ▬ Anchoring of the implant to the bone ▬ Load transfer from the prosthesis to the bone ▬ Optimal stress/strain distribution ▬ Release of antibiotics

Composition

PMMA bone cements are offered as two-component systems (powder and liquid). The polymer powder component consists of PMMA and/or methacrylate copolymers (⊡ Figs. 3.1 and 3.2). Additionally, it contains benzoyl peroxide (BPO) as initiator of the radical polymerization ⊡ Fig. 3.3. Powder components being included in the polymer beads or simply admixed to the powder. The powder also contains a radiopacifier and optionally an antibiotic (⊡ Fig. 3.3). In the liquid phase methyl methacrylate (= MMA) is the main ingredient and sometimes other methacrylates such as butyl methacrylate (⊡ Fig. 3.4). In order to be used for bone cements the methacrylates must be polymerizable. As a pre-condition for that they must bear a C=C double bond. As an activator for the forming of radicals the liquid contains an aromatic amine, such as N,N-dimethyl-p-toluidine (DmpT). Additionally, it contains an inhibitor to avoid a premature polymerization during storage and optionally a coloring agent (e.g. chlorophyll with Palacos). ⊡ Fig. 3.4. Liquid components 54 Part II · Basic Science

Radiopacity

As radiopacifier zirconium dioxide or barium sulphate are added to the bone cements. Both are not integrated in the polymer chains but remain evenly distributed in the polymer matrix. Animal studies as well as recent cell culture 3 studies show significantly higher osteolytic changes with barium sulphate as compared to the more radiopaque zirconium dioxide [8]. In spite of the low solubility of barium sulphate toxic barium ions can be set free whereas zirconium dioxide has a higher abrasive potential. These dangerous properties, however, can only come into play if the implant loosens or if loose cement particles can gain access the joint articulation. > Note: ▬ ⊡ Fig. 3.6. Chain growth Zirconium dioxide = ZrO2 ▬ Barium sulfate = BaSO4 Radiopacifiers are needed ▬ for monitoring ▬ for identification of failures

Initiator System for the Polymerization ⊡ Fig. 3.7. Chain recombination

Mixing of powder and liquid results in a reaction Because of the large amount of radicals a big number between the initiator benzoyl peroxide and the activator of rapidly growing polymer chains are generated, reach- DmpT forming radicals already at room temperature. ing molecular weights of 100,000 to 1,000,000. With the For that purpose the DmpT (liquid) causes the decom- increasing viscosity of the dough the mobility of the position of the BPO (powder) in a reduction/oxidation monomer is reduced. By recombination of two radical process by electron transfer resulting in benzoyl radi- chains the system depletes of radicals and the polymeriza- cals. These are reactive, short-living chemical entities tion dies down (⊡ Figs. 3.6 and 3.7). being able to start the polymerization by adding them- selves to the reactive C=C double bond of the MMA (⊡ Fig. 3.5). Polymerization Heat

The radical polymerization is an exothermic chemical reaction. So with the proceeding polymerization and con- sequently also growing dough viscosity the temperature increases, as 57 kJ of polymerization heat are generated per mole MMA. > Note: Radical polymerization of MMA to PMMA = exothermic reaction Heat of polymerization: 57 kJ (13.8 kcal) per mole MMA The peak temperature being observed only for a short time period during the curing of the cement was mentioned many times as the main reason for aseptic loosen- ing by heat necrosis. Especially connective tissue reactions at loose implants were interpreted as a result of a primary heat damage to the bone bed. However, the peak temperatures recorded in vitro do not correspond with those actually reached in vivo (⊡ Fig. 3.8). Clinical ⊡ Fig. 3.5. Initiation tests showed significantly lower intraoperative peaks 55 3 Chapter 3.1 · Properties of Bone Cement: What is Bone Cement?

⊡ Fig. 3.8. In vivo temperatures ⊡ Fig. 3.9. Volume shrinkage

(40–46 °C) at the bone-cement interface. The upper Molecular Weight limit is supposed to be reached only in pure cement layers of 3 mm or thicker without cancellous interdi- The molecular weight of the cured cement depends gitation [1]. mainly on the molecular weight of the polymer in the With adequate operative technique with preservation powder component and its sterilization method. The of the spongiosa it seems to be unlikely that the protein molecular weight has a significant influence on the coagulation temperature is exceeded, particularly because swelling property, the fatigue properties, the cement of the heat dissipation of the system via the implants viscosity and the working time. Contrary to ethylene and local blood circulation. The temperature peak can sterilization the gamma irradiation leads to a reduction only be influenced slightly (e. g. by liquid composition, of the molecular weight. The advantage is the high pen- different powder/liquid ratio or radiopacifier content). etration depth allowing the material to be sterilized in Those changes will, however, result in quite different the final package. working properties and, usually, a significant reduction in > Note: Factors influencing the polymer’s molecular mechanical stability. weight: ▬ Molecular weight (MW) of the raw materials used Polymerization Shrinkage in the polymer ▬ Sterilization method of the polymer powder (sterilization by irradiation results in a reduction Bone cement cannot be produced from monomer methyl to approx. 50% of the MW) methacrylate (MMA) alone; polymerization would take ▬ Molecular weight of the monomer much too long, and the polymerization shrinkage would ▬ Concentration of the initiator system or ratio ini- be extremely high. In addition, the heat occurring dur- tiator/activator, respectively ing the polymerization of the monomer could not be ▬ Progress of the temperature in the reaction controlled. ▬ Presence of regulators During the polymerization, many monomer molecules combine to few long polymer molecules. Those However, it is also known that the irradiation causes approach to one another and an inevitable volume changes of the properties of plastic materials. The highly shrink is observed. Pure MMA shrinks by 21%, that energetic rays clearly reduce the initial molecular weight means that 1 litre of MMA results in 790 ml PMMA of the polymer in the powder. Thus, one can assume that (⊡ Fig. 3.9). irradiated polymers must have had a much higher molec- By using the pre-polymerized powder component, the ular weight before the sterilization (⊡ Fig. 3.10). share of MMA in the system is reduced to 1/3. The theo- Because of the different polymer structure the han- retical shrinkage is 6–7% then. In reality it is lower due dling properties of cements are quite different before and to the cement porosity. That is why hand-mixed cements after irradiation. tend to shrink a little less than vacuum-mixed cements. In Ethylene oxide (EO)-sterilization is very complex and vivo a major part of the volume shrinkage is compensated more sensitive. The residual EO also has to be desorbed by water uptake of the cement. from the powder using a valid process. 56 Part II · Basic Science

⊡ Fig. 3.10. Methods of sterilization

Residual Monomer and Blood Circulation Reactions

On the radical polymerization of MMA a 100% conver- sion can never be reached, as the mobility of the monomer molecules decreases dramatically with the increasing dough viscosity. Hence, there is always an amount of 2–6% of residual monomer in a cement matrix right after setting [5] (⊡ Fig. 3.11). This amount decreases within 2–3 weeks to about 0.5%, mainly (about 80%) by slow post-polymerization. The minor part of the residual MMA enters the blood circulation and then leaves the body by simple respiration or being metabolized via the Krebs cycle. Ever since bone cements have been introduced, some negative effects on the cardiorespiratory system have been ⊡ Fig. 3.11. Residual monomer observed during the operation, even rarely leading to a patient’s death. Although these phenomena have often been attributed to MMA, it is now well established that tives. Water-uptake has a decisive influence on the soften- the intramedullar increase of pressure during cement and ing of a plastic and thus on the glass transition temperature prosthesis insertion is the main pathological mechanism (⊡ Fig. 3.12). The softening effect is due to the upcoming [4] leading to embolisation of bone marrow and fat as micro-Brown movement and leads to changed elasticity shown during with the use of transoesophageal, two- modulus, heat conduction and thermal expansion. dimensional echocardiography. In a dry state, PMMA bone cements have a relatively high glass transition temperature (about 90–100 °C) compared to the body temperature. After its setting, the Glass Transition Temperature cement is brittle with a high elasticity modulus and high cohesiveness. After the implantation into the body with its Plastics change their physical state with rising temperature liquids at 37 °C, the cement will be water-saturated within from glass-like/brittle to rubber-elastic. The temperature a few weeks. Thus by the plasticizing effect the glass tran- range in which this change occurs is characterized by the sition temperature drops. so-called glass transition temperature. It depends on the The difference between dry and water-saturated sam- chemical nature of the polymer and the presence of addi- ples of bone cements is about 20 °C. Since the glass 57 3 Chapter 3.1 · Properties of Bone Cement: What is Bone Cement?

⊡ Fig. 3.12. Glass transition temperature

transition temperature is only a measure for the transition range, polymers can already slump below that temperature. With the growing rubber-elastic properties the cements show a higher tendency to creep, and so the implants may „sink« deeper into the cement mantle. The common bone cements on the market show a glass transition temperature of about 70 °C after water saturation. With this temperature clearly above the body temperature a safe use of the cements is assured [5].

⊡ Fig. 3.13. ISO 5833 mechanical tests Creep Behaviour

Acrylic bone cements also show plastic properties. So it is physically possible that they intrude slowly into cavities after their curing and seal them. This important property gives them a high flexibility in the bone. Therefore, the creep behaviour is taken as an additional criteria for bone cement testing. The interfaces between bone and bone cement as well as bone cement and prosthesis are mechanical boundar- ies. The bone cement as the central part functions as an elastic buffer.

⊡ Fig. 3.14. Fatigue test Mechanical Tests

Unfortunately, a lot of literature data about the mechan- sive strength, bending strength and bending modulus are ics of bone cements cannot be compared because of the tested (⊡ Fig. 3.13). lack of information about preparation and storage of the Beside these static tests dynamic studies are per- test specimens and the test method. According to the formed, too, such as fatigue testing (⊡ Fig. 3.14). Different internationally accepted standard ISO 5833, compres- variants are possible: tensile, compression or bending. 58 Part II · Basic Science

Mostly, the fatigue testing is done by bending as the Already in the mixing phase great differences are observed necessary equipment is relatively simple. Such studies for different cements. Some are mixed easily, others are are very time-consuming, being done until 1,000,000 or hard to mix because of a high initial viscosity. As a con- better 10,000,000 cycles are reached. To get a correla- sequence, many air bubbles can be incorporated into the tion to the practical life, one assumes an annual num- dough at this early stage leading to a high porosity of the ber of 1,000,000 double steps (= 2,000,000 steps). Thus, cement endangering the mechanic stability. 10,000,000 reached cycles would be equivalent to a time 3 > Note: ISO 5833 requirement period of five years. Anyway, such tests can only give a »It is suggested that a graphical representation rough idea of the quality of a cement especially as their of the effect of temperature on the length of the properties change under physiologic conditions (body phases in cement curing, prepared from experi- temperature and fluids) and in so far the clinical relevance mental data on the particular brand of cement, of test standards must be challenged [8]. be provided.« The design of the mixing vessel and spatula as well as Working Behaviour and Viscosity the mixing speed and number of strokes per minute also influence the homogeneity of the dough. The longer After mixing of the powder and the liquid components, a and the more vigorously it is mixed the more porous it doughy mass is formed by swelling and dissolution. Because becomes. The waiting phase allows the cement to come to of the initiated radical polymerization the viscosity increas- a non-sticky consistency ready to use. It is then that the es continuously until the complete hardening/curing of the porosity can be reduced significantly by smooth manual cement. The user must have detailed knowledge about the kneading. viscosity course to plan the operation optimally. During the application phase the surgeon brings the dough into the bony cavity. The dough must be of moder- > Note: Working properties ate viscosity and non-sticky if manually inserted. The dif- ▬ The viscosity is the most important handling ferences between the cements in this context are consid- property for the surgeon erable. It must be mentioned, however, that regardless of ▬ The viscosity increases continually during the the manufacturer’s classification as low, medium or high working period viscous all cements start with a low-viscous phase chang- ▬ The timing for the injection of the cement is ing to higher viscosity more or less rapidly, depending on important for the success of the surgery the viscosity type. The progression of the viscosity depends on the cement > Note: Factor influencing the viscosity composition, the powder/liquid mixing ratio, the humid- ▬ Swelling and dissolution behaviour of the ity and especially on the temperature of the dough and polymer powder in the liquid monomer the surroundings. ▬ The ratio of the powder and the liquid On the use of bone cements different phases are dis- ▬ The temperature of tinguished: mixing phase, waiting phase, application phase the powder and the liquid and setting phase: the mixing equipment ▬ mixing phase: the operating room – wetting and polymerization, = Result in low- and high-viscous cements – cement relatively liquid (low viscous), – few chains, very movable; Using mixing systems, the phases can change significantly ▬ waiting phase: because the user does not need to wait for the dough – chain propagation, to loose its stickiness. Nevertheless, the viscosity at the – cement less liquid, beginning of the application phase must not be too low. – more chains, less movable; Otherwise the inserted dough might not withstand the ▬ working phase: bleeding pressure in the femur with the consequence of – chain propagation, blood entrapment within the cement representing poten- – reduced movability, tial areas of weakness with increased fracture risk. This – increase of viscosity phenomenon is the main problem when applying low – heat generation; viscosity cements with their short application phase too ▬ setting phase: early. Normal or high viscosity cements in this regard – chain growth finished, seem to be more user-friendly and forgiving resulting in – no movability, better long-term performance [1, 9]. – cement hardened, – high temperature. 59 3 Chapter 3.1 · Properties of Bone Cement: What is Bone Cement?

Pre-Chilling of Cement Components Take Home Messages I I ▬ Acrylic bone cement is used for implant fixation The chilling of components or low ambient temperature and local release of antibiotics. slow down the polymerization and reduce the viscosity ▬ Bone cements mainly consist of PMMA or copo- and vice versa. Pre-chilling as well as the application of lymers in the powder and methyl methacrylate in vacuum mixing reduce the cement porosity and improve the liquid. the mechanics of the cured cement. Such mixing sys- ▬ Added zirconium dioxide or barium sulphate pro- tems ( chapter 4) consist of a mixing cartridge with a vide radiopacity. mixing element and the vacuum equipment with pump, ▬ Benzoyl peroxide (powder) and N,N-Dimethyl-p- tubing and charcoal filter to absorb the MMA vapours. toluidine (liquid) are the initiators of the polymer- The mixing cartridge is also the application unit so that ization process. the cement need not be transferred to another unit. The ▬ The polymerization heat of the exothermic radical dough is injected with an appropriate cement gun. polymerization of methyl methacrylate is 57 kJ per Vacuum mixing systems can have a positive influ- mole. ence on the cement quality and thus on the durability of ▬ The polymerization shrinkage of acrylic bone cemented prostheses. The basic requirement, however, cements is about 3–5%. is the correct usage of the system. With poor handling ▬ Working behaviour and fatigue properties depend leading to insufficient mixing or low vacuum, the qual- on molecular weight (the higher the molecular ity of the cement may be poor. Also the correct mixing weight the better). sequence (of powder and liquid) must be regarded which ▬ As the radical polymerization is never complete, ⊡ does not always seem to be the case ( Fig. 3.15). residual monomer remains in the hardened If the vacuum equipment is insufficient or used incor- cement. Serum traces of MMA are respired or rectly, no positive effect on the porosity can be expected. metabolized rapidly in the Krebs cycle. A vacuum pressure too high or applied for too long, on ▬ Static properties according to ISO 5833 as well as the other hand, may cause the monomer to boil already dynamic properties (fatigue) provide important at room temperature as its vapour pressure at 23 °C is 38 mechanical data. kPa. Boiling MMA of course leads to bubbles/pores in the ▬ Many factors, especially the temperature, influence cement. the dough viscosity and the working properties, A variety of different vacuum mixing systems are which are most important to the user. offered on the market. Standard systems come empty and have to be filled with the desired cement components. A new trend are the pre-packed systems: semi-pre-packed systems contain only the powder component whilst full- References pre-packed also contain the liquid in a special construct. The latter systems avoid that the user comes in direct 1. Breusch SJ (2001) Cementing technique in total hip replacement: contact with the cement components. Vacuum mixing Factors influencing survival of femoral components. In: Walen- kamp GHIM, Murray DW (eds) Bone cements and cementing systems have proven of value for most surgeons nowa- technique. Springer, Berlin Heidelberg New York Tokyo days. Newer studies show the systems with horizontal 2. Charnley J (1960) Anchorage of the femoral head prostheses of mixing screw to be superior and favour the collection of the shaft of the femur. J Bone Joint Surg 42 Br: 28–30 the dough under vacuum. 3. Charnley J (1970) Acrylic cement in orthopaedic surgery. Williams and Wilkins, Baltimore 4. Crout DMG, Corkill JA, James ML, Ling RSM (1979) Methylmethac- rylate metabolism in man. Clin Orthop Rel Res 141: 90–95 5. Ege W, Kühn KD, Tuchscherer C, Maurer H (1998) Physical and chemical properties of bone cements. In: Walenkamp GHIM (ed) Biomaterials in surgery. Georg Thieme, Stuttgart 6. Judet J, Judet R (1956) The use of an artificial femoral head for arthroplasty of the hip joint. J Bone Surg 32 B: 166 7. Kleinschmitt O (1941) Plexiglas zur Deckung von Schädellücken. Chirurg 13: 273 8. Kühn KD (2000) Bone cements. Springer, Berlin Heidelberg New York Tokyo 9. Kühn KD (2001) Handling properties of polymethacrylate bone cements. In: Walenkamp GHIM, Murray DW (eds) Bone cements and cementing technique. Springer, Berlin Heidelberg New York Tokyo

⊡ Fig. 3.15. Viscosity curves