Relative roles of cement molecular weight and mixing method on the fatigue performance of acrylic bone cement: Simplex P versus Osteopal

The weight-average molecular weight (MW(w)) of a cement and the method used to mix its powder and liquid monomer constituents have been identified in the literature as key variables that affect mechanical properties of the fully polymerized cement that are relevant to its performance as a grouting agent in cemented arthroplasties. The goal of the present work was to identify which of these two variables exerts the greater effect in the case of fully reversed tension-compression fatigue performance. A judicious choice of cement brands, Surgical Simplex P and Osteopal, and the use of hand versus vacuum mixing, permitted this identification to be achieved. Three key observations were made in this work. First, for a given cement, the fatigue performance of vacuum-mixed specimens is far superior to that of hand-mixed ones, which may be a consequence of the substantially lower percentage areal porosity of the former specimens. Second, regardless of the mixing method, the fatigue performance of Osteopal outstrips that of Simplex P, a result that is attributed to the much higher MW(w) of the former cement. Third, hand-mixed Osteopal outperforms vacuum-mixed Simplex P (especially at low alternating stress levels), indicating that MW(w) of a bone cement is more influential than mixing method on its fatigue performance.     

Effect of mixing method and storage temperature of cement constituents on the fatigue and porosity of acrylic bone cement.

The influence of the storage temperature of the cement constituents prior to mixing (21 vs. 4 degrees C) and the mixing method (hand mixing vs. vacuum mixing) on the uniaxial tension-compression fatigue performance and porosity of Palacos R acrylic bone cement was studied. The fatigue results were analyzed using the three-parameter Weibull equation. The fatigue performance was expressed as an index I, which was defined as the product of the Weibull characteristic fatigue life and the square root of the Weibull slope. Statistical analyses of these results show that although the mixing method (for a given storage temperature) exerts a significant influence on the fatigue performance and areal porosity, the effect of storage temperature (for a given mixing method) on either of these parameters is not significant.     

The influence of the viscosity classification of an acrylic bone cement on its in vitro fatigue performance

The goal of the present work was to investigate the influence of the viscosity classification of an acrylic bone cement on its in vitro fatigue performance, as determined in fully-reversed tension-compression (+/-15 MPa) fatigue tests. The test matrix comprised six commercially available bone cements [Orthoset1, (OS1), Orthoset(R)3 (OS3), CemexRX (CRX), Cemex XL (CXL), Palacos R (PR) and Osteopal (OP)], two methods of mixing the cement constituents (hand-mixing and vacuum-mixing), two methods of fabricating the test specimens (direct molding and molding followed by machining), two specimen cross-sectional shapes (rectangular or "flat" and circular or "round"), and four test frequencies (1, 2, 5, and 10 Hz). In total, 185 specimens, distributed among 20 sets, were tested. The test results (number of fatigue stress cycles, N_f) were processed using the linearized transformation of the three-parameter Weibull distribution, whence estimates of the Weibull mean, N_[WM], were obtained. Statistical analysis of the ln N_f results (Mann-Whitney test; alpha<0.05) and a comparison of the N_[WM] estimates for specimen sets in which the formulations have essentially the same composition but different viscosity classification (namely, OS1 versus OS3, CRX versus CXL, and PR versus OP) showed that, in the majority of the comparisons carried out, the viscosity classification of a bone cement does not exert a significant influence on its in vitro fatigue performance.     

Effect of fabrication pressure on the fatigue performance of Cemex XL acrylic bone cement

During a cemented arthroplasty, the prepared polymerizing dough of acrylic bone cement is subjected to pressurization in a number of ways; first, during delivery into the freshly prepared bone bed, second, during packing in that bed (either digitally or with the aid of a mechanical device), and, third, during the insertion of the prosthesis. Only a few studies have reported on the influence of the level of pressurization experienced during these events (which, depending on the cementing technique used, has been put at between 8 and 273 kPa) on various properties of the cement. That was the focus of the present study, in which the fully reversed tension-compression (+/-15 MPa; 5 Hz) fatigue lives (expressed as number of cycles to fracture, N(f)) of rectangular cross-sectioned "dog-bone" specimens (Type V, per ASTM D 638) fabricated from Cemex XL cement, at pressure applied continuously to the cement dough during curing in the specimen mold, p=75,150, and 300 kPa, were determined. The N(f) results were analyzed using the linearized transformation of the three-parameter Weibull relationship to obtain estimates of the Weibull mean, N(WM), which was taken to be the index of fatigue performance of the specimen set. Over the range of p studied, N(WM) increased as p increased (for example, from 329,118 cycles when p was 75 kPa to 388,496 cycles when p was 300 kPa); however, the increase was not significant over any pair of p increment steps (Mann-Whitney U-test; alpha<0.05).     

Effect of test frequency on the in vitro fatigue life of acrylic bone cement

The goal of the present work was to test the hypothesis that test frequency, f, does not have a statistically significant effect on the in vitro fatigue life of an acrylic bone cement. Uniaxial constant-amplitude tension-compression fatigue tests were conducted on 12 sets of cements, covering three formulations with three very different viscosities, two different methods of mixing the cement constituents, and two values of f (1 and 10 Hz). The test results (number of fatigue stress cycles, N(f)) were analyzed using the linearized form of the three-parameter Weibull equation, allowing the values of the Weibull mean (N(WM)) to be determined for each set. Statistical analysis of the lnN(f) data, together with an examination of the N(WM) estimates, showed support for the hypothesis over the range of f used. The principal use and explanation of the present finding are presented.     

Influence of mixing techniques on the physical properties of acrylic bone cement

Palacos R bone cement was prepared using three commercially available mixing techniques, first generation, second generation and third generation, to determine the mechanical properties and porosity contents of the bone cement. The compressive strengths, bending strengths and flexural moduli were expressed as a function of void content. The volume of pores within the cement structure was found to be a contributing factor to the physical properties of acrylic bone cement. The lower the volume of voids in the cement the better the compressive and flexural properties, hence stronger bone cement. It was found that the best results were obtained from cement that had been mixed using the Mitab Optivac or Summit HiVac Syringe systems at a reduced pressure level of between -72 and -86 kPa below atmospheric pressure, resulting in cement of porosity 1.44-3.17%; compressive strength 74-81 MPa; flexural modulus 2.54-2.60 GPa; and flexural strength 65-73 MPa.     

Effect of test specimen cross-sectional shape on the in vitro fatigue life of acrylic bone cement

Constant-amplitude uniaxial tension-compression fatigue tests were conducted on specimens fabricated from 12 sets of acrylic bone cements, covering cement formulations with three different viscosities (so-called "high-", "medium-" and "low-viscosity" varieties), two different methods of mixing the cement constituents (so-called "hand-" and "vacuum-mixed" methods) and two test specimen shapes (rectangular-cross-sectioned or "flat" and circular-cross-sectioned or "round"). The test results-namely, the number of fatigue stress cycles, N(f)-were analyzed using the linearized transformation of the three-parameter Weibull relationship, allowing the values of the Weibull mean, N(WM), to be determined for each set. Values ranged from 14,300 to 1,284,331 for the round specimen sets and from 2898 to 72,960 for the flat specimen sets. Statistical analysis of the ln N(f) data, together with an examination of the N(WM) values, showed that, for any combination of cement formulation and mixing method, round specimens had significantly longer fatigue lives compared to flat ones. These results are explained in terms of two factors. The first is the smaller surface area of the waisted zone in the round specimens compared to that in the flat specimens (nominal value of 157mm(2) versus nominal value of 185mm(2)), leading to the possibility of fewer crack initiation sites on the round specimens compared to the flat ones. Secondly, it is postulated that the crystallinity of the round specimens was higher than that of the flat ones, a consequence of the significantly lower measured residual liquid monomer contents of the former compared to the latter (3.40+/-1.28wt%/wt compared to 3.81+/-1.48wt%/wt). The significance of the present finding is that it indicates that, for a set of bone cement formulation and experimental conditions, discriminating fatigue test results are more likely to be obtained if flat, rather than round, test specimens are used.     

Relative influence of composition and viscosity of acrylic bone cement on its apparent fracture toughness

The composition and viscosity of an acrylic bone cement have both been identified in the literature as being parameters that affect the mechanical properties of the material and, by extension, the in vivo longevity of cemented arthroplasties. The objective of the present study was to determine the relative influence of these parameters on a key cement mechanical property; namely, its fracture toughness. Two sets of cements were selected purposefully to allow the study objective to be achieved. Thus, one set comprised two cements with very similar compositions but very different viscosities (Cemex RX, a medium-viscosity brand, and Cemex Isoplastic, a high-viscosity brand) while the other set comprised two cements with similar viscosities but with many differences in composition (Cemex Isoplastic and CMW 1). Values of the fracture toughness (as determined using chevron-notched short rod specimens) [K(ISR)] obtained for Cemex RX and Cemex Isoplastic were 1.83 +/- 0.12 and 1.85 +/- 0.12 MPa square root(m), respectively, with the difference not being statistically significant. The K(ISR) values obtained for Cemex Isoplastic and CMW 1 were 1.85 +/- 0.12 and 1.64 +/- 0.18 MPa square root(m), respectively, with the difference being statistically significant. Thus, the influence of cement composition on its K(ISR) is more marked relative to the influence of cement viscosity. Explanations of this finding are offered, together with comments on the implications of the results for the in vivo longevity of cemented arthroplasties.     

Comparison of two methods of fatigue testing bone cement

Two different methods have been used to fatigue test four bone cements. Each method has been used previously, but the results have not been compared. The ISO 527-based method tests a minimum of 10 samples over a single stress range in tension only and uses Weibull analysis to calculate the median number of cycles to failure and the Weibull modulus. The ASTM F2118 test regime uses fewer specimens at various stress levels tested in fully reversed tension–compression, and generates a stress vs. number of cycles to failure (S–N) or Wöhler curve. Data from specimens with pores greater than 1 mm across is rejected. The ISO 527-based test while quicker to perform, provides only tensile fatigue data, but the material tested includes pores, thus the cement is closer to cement in clinical application. The ASTM regime uses tension and compression loading and multiple stress levels, thus is closer to physiological loading, but excludes specimens with defects obviously greater than 1 mm, so is less representative of cement in vivo. The fatigue lives between the cements were up to a factor 15 different for the single stress level tension only tests, while they were only a factor of 2 different in the fully reversed tension–compression testing. The ISO 527-based results are more sensitive to surface flaws, thus the differences found using ASTM F2118 are more indicative of differences in the fatigue lives. However, ISO 527-based tests are quicker, so are useful for initial screening.     

Investigation of fatigue crack growth in acrylic bone cement using the acoustic emission technique

Failure of the bone cement mantle has been implicated in the loosening process of cemented hip stems. Current methods of investigating degradation of the cement mantle in vitro often require sectioning of the sample to confirm failure paths. The present research investigates acoustic emission as a passive experimental method for the assessment of bone cement failure. Damage in bone cement was monitored during four point bending fatigue tests through an analysis of the peak amplitude, duration, rise time (RT) and energy of the events emitted from the damage sections. A difference in AE trends was observed during failure for specimens aged and tested in (i) air and (ii) Ringer's solution at 37 degrees C. It was noted that the acoustic behaviour varied according to applied load level; events of higher duration and RT were emitted during fatigue at lower stresses. A good correlation was observed between crack location and source of acoustic emission, and the nature of the acoustic parameters that were most suited to bone cement failure characterisation was identified. The methodology employed in this study could potentially be used as a pre-clinical assessment tool for the integrity of cemented load bearing implants.     

Estimation of the minimum number of test specimens for fatigue testing of acrylic bone cement

In the literature on fatigue testing of acrylic bone cements, data sets of various sizes have been used in different test series for the same cement formulation. There are two important consequences of this situation. First, it means that some test series last much longer than others, with all the implications for the cost of testing. Second, it makes drawing conclusions about the fatigue performance of a cement, based on the results of different literature series, a problematic issue. Clearly then, a recommendation as to what should be the minimum number of test specimens to use that would allow for confidence in the results of the statistical treatment of the test results (Gmin) would be desirable. In the present work, a method that could be used to culminate in such a recommendation is described. This method involves (i) obtaining experimental fatigue test results and (ii) analyzing those results using the Weibull probability distribution function and other statistical methods. This methodology is illustrated using fatigue life results obtained from uniaxial tension-compression fatigue tests on specimens fabricated from the polymerizing dough of one commercially available acrylic bone cement. For a tolerable error of 5%, we estimated Gmin to be either 7 (if the fatigue life results are treated using the two-parameter Weibull distribution function) or 11 (if the fatigue life results are treated using the three-parameter Weibull distribution function). To be on the conservative side, we therefore recommend that Gmin be 11. Three key limitations of the methodology presented here are discussed.     

Influence of initial component temperature on the apparent viscosity and handling characteristics of acrylic (PMMA) bone cement

The flow and polymerization characteristics of poly(methylmethacrylate) (PMMA) bone cement can be changed by manipulating the temperature of the bone cement components or the environment that they are prepared in. To quantify the effects of the initial component temperature (T(ic)) of acrylic bone cement on the rheological and handling characteristics, ASTM F451-99a compliant methods and clinically relevant testing methods were utilized. A rheometer was designed and fabricated using the dimensions of a clinical, commercially available, cement gun and nozzle. The influence on the apparent viscosity and handling characteristics (setting time, working time, and peak exotherm temperature) for a high viscosity (HV) commercially-available acrylic bone cement, Palacos R, were determined. The values of T(ic) used were 23 degrees C (room), 6 degrees C (refrigerator), and -14 degrees C (freezer). Using the apparent viscosity of a medium viscosity (MV) bone cement as a benchmark (Simplex P at room temperature), it was found that by adjusting the T(ic) the HV cement was able to mimic the flow characteristics of the MV cement. Lowering the T(ic) lowered the apparent viscosity of the bone cement. The effects of T(ic) on the polymerization of bone cement were studied in dynamic and static conditions. The dynamic test recorded temperature and torque from stirring resistance. Setting times were also determined using the ASTM exotherm mold method. The setting times determined by the dynamic testing conditions were consistently shorter than those determined by the ASTM method. Lowering the T(ic) increased the working and setting times; however, it did not have a significant effect on the peak exotherm temperature.     

Effect of lithotriptor treatment on the fracture toughness of acrylic bone cement.

Extracorporeal shock wave lithotripsy (ESWL) has now been established as an efficacious non-invasive modality for the management of renal calculi and has shown promise for management of other types of stone, as well. Following on from these successes, ESWL has recently been proposed for use in the preliminary stages of revision of cemented total hip joint replacements as a means of breaking up the cement mantle. It is useful, therefore, to examine the effect of shock waves on pertinent mechanical properties of the cement. This study utilizes the chevron-notch short-rod specimen and a commercially available test system to obtain the values of one such property, namely fracture toughness, of Palacos Radiopaque bone cement before and after treatment with shock waves delivered from a lithotriptor. The fracture toughness drops by about 14% following the shock wave treatment, thus confirming the possibility that ESWL can be used, as indicated earlier, in revision arthroplasty.     

Effect of loading rate on the apparent fracture toughness of acrylic bone cement

In this study, a determination is made of the effect of loading rate, v (0.1 mm min(-1) versus 1.0 mm min(-1) versus 10 mm min(-1)) on the value of the plane strain fracture toughness, K(Ic), of three commercial formulations of acrylic bone cement (Osteopal), CMW3, and Copal), that are characterized as "low-", "medium-", and "high-" viscosity brands, respectively). For all formulations, K(Ic) increases with increase in v. However, while this trend is statistically significant for CMW3 and Copal, this is not so for Osteopal. The CMW3 and Copal results are explained in terms of changes of the molecular relaxation transitions in the cement and the thermal state at the crack tip of the test specimen. Two implications of the findings are discussed. In the case of Osteopal, a recommendation for further study is made.     

Effect of vacuum mixing on the mechanical properties of antibiotic-impregnated polymethylmethacrylate bone cement

Polymethylmethacrylate bone cement, containing either no added antibiotic, 0.5 g of Vancomycin, 1.0 g of Vancomycin, or 1.0 g of Tobramycin, was mixed either in air or a vacuum chamber. Following storage in a water bath at 37 degrees C for 48 h, the specimens were tested in four-point bending. The porosity of the specimens was assessed radiographically, and their antibacterial activity was monitored for 21 days. The bending strength of the vacuum mixed specimens containing no antibiotic was 40% greater than that of similar air-mixed specimens. However, there were no significant differences in the bending strength of either the air- or vacuum-mixed specimens when any of the antibiotic dosages were added. The bending modulus of the vacuum-mixed specimens, containing no antibiotic, was significantly greater than the moduli of all the other specimen groups which did not differ from each other. Vacuum mixing reduced the apparent porosity of the specimens fivefold, and while the addition of antibiotic did not effect porosity of the air-mixed specimens, that of the vacuum-mixed specimens was doubled. Although initial rapid decreases were seen, leaching of antibiotic from the cement and antibacterial activity continued through the 21-day monitoring period.     

Influence of oscillatory mixing on the injectability of three acrylic and two calcium-phosphate bone cements for vertebroplasty

Injecting acrylic and, increasingly, calcium-phosphate cements into the porous bone structure is an emerging procedure, referred to as vertebroplasty, for the augmentation of osteoporotic vertebrae. Despite the benefits of vertebroplasty, it has limitations. The limitations of interest in this study are the injectability of bone cements and their mixing variability (i.e., low reproducibility of resulting viscosity). The objective of this study is to investigate the effect of oscillatory versus manual mixing on cement viscosity and mixing variability. Five cements are tested: (a) Vertebroplastic, (b) DP-Pour, (c) Antibiotic Simplex, (d) chronOS Inject, and (e) Biopex. Compared to manual mixing, oscillatory mixing significantly decreased the mean viscosity and the mixing variability, which was inferred from the coefficient of variation. For example, under oscillatory mixing, the viscosity and the variability for Vertebroplastic decreased to one-third of the corresponding values for manual mixing. Similar results were obtained for the other cements. The decrease in viscosity is attributed to the pseudo-plastic behavior of bone cements. The decrease in the variability of cement viscosity was attributed to greater dispersive mixing of the cement components under oscillatory mixing. The decrease in viscosity eases the injection by reducing the pressure required. The decrease in the variability of cement viscosity increases reproducibility of the cement injection. Oscillatory mixing appears to have the potential to contribute to improving vertebroplasty.     

Bisphosphonate-laden acrylic bone cement: mechanical properties, elution performance, and in vivo activity

Cemented total hip replacements generally fail after 10-20 years, often due to implant loosening from bone resorption. Bisphosphonates such as zoledronic acid (ZA) and pamidronate (PAM) are potent inhibitors of bone resorption. The local delivery of bisphosphonates via acrylic bone cement could decrease osteolysis and prolong implant lifespan. Conflicting studies suggest that bisphosphonate loading may or may not reduce the mechanical properties of acrylic bone cement. We assayed acrylic bone cement laden with ZA or PAM at different concentrations and diluent volumes. Four-point bend testing and compressive testing indicated that high volumes of diluent (with or without bisphosphonate) significantly reduced bending modulus and compressive strength. Radiography and electron microscopy indicated that high diluent volumes generated abnormal acrylic bone cement structure. After 6 weeks of incubation in saline, only 0.9% w/w of the total bisphosphonate incorporated in acrylic bone cement eluted in vitro, indicating a slow elution rate. In vivo testing was performed using a rat model. Cement cylinders were inserted into incisions in rat distal femora and ZA delivered locally (via elution from acrylic bone cement) or systemically (via injection). At 4 weeks postoperatively, dual energy X-ray absorptiometry demonstrated no significant increase in local bone mineral density (BMD) adjacent to ZA-laden implants. In contrast, systemic ZA delivery (0.1 mg/kg) led to a large (48.6%) and significant increase in BMD. Thus, systemic delivery appears more effective than local delivery.     

Influence of mixing method on the cement temperature-mixing time history and doughing time of three acrylic cements for vertebroplasty

Acrylic cements are increasingly being used to augment osteoporotic vertebrae in a procedure called vertebroplasty. Two significant factors that may complicate the use of acrylic cements are: (a) short handling time, which may result in insufficient filling of the vertebra; and (b) exothermic setting (curing) behavior, which may result in thermal damage of the surrounding tissue. It has been previously reported that mixing the cement components under oscillation, as compared to manual mixing, increases the handling time. More specifically, it seems that oscillatory mixing slows down the cement polymerization process and, consequently, widens the time window during which cement is injectable. However, the effect of oscillatory mixing on the exothermic setting behavior of cement undergoing polymerization has not been examined. In this study, the exothermic setting behavior of three commercially available acrylic cements--Antibiotic Simplex, DP-Pour&trade, and Vertebroplastic--were examined for both manual and oscillatory mixing methods. For each combination of cement and mixing method, the parameters that were measured were the exothermic setting curve (and hence the cement setting temperature and setting time) and the cement doughing time. It was found that oscillatory mixing had no significant effect on any of these parameters. Based on the results of this study, it can be concluded that, for the tested cements, the setting process is a reaction-controlled process rather than a diffusion-controlled one. Clinically, this implies that oscillatory mixing may be used to increase the working period for acrylic cements without increasing the risk of thermal damage to surrounding tissue.     

Influence of powder particle size distribution on complex viscosity and other properties of acrylic bone cement for vertebroplasty and kyphoplasty

For use in vertebroplasty and kyphoplasty, an acrylic bone cement should possess many characteristics, such as high radiopacity, low and constant viscosity during its application, low value of the maximum temperature reached during the polymerization process (T(max)), a setting time (t(set)) that is neither too low nor too high, and high compressive strength. The objective of this study was to investigate the influence of the powder particle distribution on various properties of one acrylic bone cement; namely, residual monomer content, T(max), t(set), complex viscosity, storage and loss moduli, injectability, and quasi-static compressive strength and modulus. It was found that the formulations that possessed the most suitable complex viscosity-versus-mixing time characteristics are those in which the ratio of the large poly(methyl methacrylate) beads (of mean diameter 118.4 microm) to the small ones (of mean diameter 69.7 microm) was at least 90% w/w. For these formulations, the values of the other properties determined were acceptable.     

Effect of surface modification of polymer beads on the mechanical properties of acrylic bone cement

The effect of surface modification of polymer filler on the static mechanical properties of acrylic bone cement was studied. The surface of polymer beads was modified with carboxylic and amino groups by photochemical reaction with azide compounds. Monomer modifiers (maleic anhydride, methacrylic acid and p-aminostyrene) are attached to the functionalized surface of polymer beads. Functional allyl groups, which are capable of the graft polymerisation reaction, are attached to the surface via photochemical reaction with N-(2-nitro-4-azidophenyl)-N-(-propen) amine. This approach to bone cement provides the additional covalent bonds between the polymer beads and the inter-bead matrix. The static mechanical properties of bone cements containing modified polymer beads were investigated and compared with the static mechanical properties of unmodified cements. The absolute values of compressive strength for the modified and unmodified cements were found to be similar. An increase in flexural strength for the modified cements (dry and after water storage) was observed. The structure of the surface functional groups affects the methyl methacrylate grafting resulting in a higher value of flexural strength for the maleic anhydride- and p-aminostyrene-modified cements. The scanning electron microscopy examination of the fracture surface of the cement samples showed an improvement of the adhesion between the beads and the matrix after modification.