|
|
Journal
of
Bone
and
Joint
Surgery
-
British
Volume,
Vol
89-B,
Issue
7,
851-857. The role of polymethylmethacrylate bone cement in modern orthopaedic surgeryJ. C. J. Webb, BSc(Hons), MBChB(Hons), FRCS(Trauma & Orth), Orthopaedic Specialist Registrar1; and R. F. Spencer, MD, FRCS, FCS(SA)Orth, Consultant Orthopaedic Surgeon2
1
Avon
Orthopaedic
Centre,
Southmead
Hospital,
Bristol
BS10
5NB,
UK. Correspondence should be sent to Mr J. C. J. Webb; e-mail: jcjwebb{at}doctors.org.uk
This article describes the current uses and limitations of polymethylmethacrylate in orthopaedic surgery. It focuses on its mechanical and chemical properties and links these to its clinical performance. The behaviour of antibiotic-loaded bone cement are discussed, together with areas of research that are now shedding light upon the behaviour of this unique biomaterial.
Polymethylmethacrylate was unveiled by the chemical industry in 1843 and named ‘acide acrylique’ on account of the acrid smell of the monomer.5 In 1936 it was noted that mixing ground polymer with monomer produced a dough that could be manipulated and moulded; hence it became one of the early biomaterials. Early applications were in dentistry.6 In 1945 and 1950 respectively, Scales and Herschell7 and Judet and Judet8 employed PMMA prostheses of the femoral head for arthritis of the hip. Its use as a grout to improve implant fixation was pioneered in 1953 by Haboush.9 However, the major breakthrough in the use of PMMA in total hip replacement (THR) was the work of Charnley10 in 1970 who used it to secure fixation of the acetabular and femoral components and to transfer loads to bone.
The
structure
of
methylmethacrylate
monomer
allows
polymerisation
at
room
temperature
to
produce
solid
PMMA.11
The
avidity
of
the
polymer
to
dissolve
in
monomer
aids
this
reaction.
The
contents
of
commercial
packs
of
cement,
including
additives,
are
listed
in
Table
I
Table I. Commercial constituents of bone cement
The cement must be liquid enough during the working phase to be forced through a delivery device and then flow under pressure to penetrate the interstices of cancellous bone, achieving micro-interlock.10,15 Manufacturers produce cements of varying viscosities:14
Low.
Medium.
High. High viscosity cements are therefore forgiving for the surgeon and are in predominant use in the United Kingdom.16 However, the rates of curing are very sensitive to environmental factors. Low ambient temperatures during storing and mixing,17 and high humidity both prolong setting time.18
The polymerisation of PMMA is exothermic.14 Catalysts form free radicals which break the covalent C=C bonds of the monomer, allowing them to bind to the lengthening polymer chains. This reaction releases 52 KJ/mole of monomer, equating to heat production of 1.4 to 1.7 x 108 J/m3 of cement.14 The production of heat by the curing cement has been studied in vitro and in vivo and modelled using finite element analysis.19 In vitro studies have shown that the production of heat is increased by thicker cement mantles, higher ambient temperatures and an increased ratio of monomer to polymer.17 Recorded temperatures range between 70°C and 120°C.20 Collagen denatures with prolonged exposure to temperatures in excess of 56°C, and the risk of causing thermal damage to bone has been raised by several authors.20,21 However, in vivo studies have recorded lower peaks of temperature.14 In 1977, Reckling and Dillon22 measured the temperature at the bone cement interface in 20 THRs. The maximum temperature was 48°C but the range of the rise was from 3° to 17°C. These modest rises were attributed to the cooling effects of the local blood supply, the metallic stem, the large surface area of the interface and poor thermal conductivity of the cement. Harving, Soballe and Bunger23 recorded temperatures above 56°C but only for two to three minutes. Even if such temperatures may sometimes be reached, animal studies have indicated no adverse effects.24 Nevertheless, concerns regarding thermal and chemical injury persisted and much effort was expended on low exotherm alternatives. Boneloc (Biomet Inc., Warsaw, Indiana) was a methylmethacrylate/n-decylmethacrylate/isobotinyl-methacrylate (MMA/DMA/IBMA) co-polymer cement. Its setting temperature was 58°C in vitro.25 However, clinical results were poor with a rate of aseptic loosening of 34% at three years because of abnormal visco-elastic behaviour.26 Chemical changes made to the composition of cement can therefore have profound effects upon function, as can manipulation of the mix of the constituents, a feature that has been exploited for specific indications such as percutaneous vertebroplasty.
Percutaneous vertebroplasty was originally developed as a treatment for angiomas,3 but its application to the osteoporotic spine has been shown to provide significant and prolonged relief of pain.4 It controls the symptoms of compression fractures by recreating mechanical stability.28 The technique involves the percutaneous transpedicular injection of low viscosity biomaterial into the vertebral body guided by an image intensifier. It has become common practice for clinicians to alter the mix constituents of the PMMA in order to facilitate the procedure.29 To ease injection they reduce viscosity by increasing the liquid to powder proportions of the mix. As detailed earlier, this would seem likely to increase the maximum setting temperature and setting time of cement,11 a cause for concern when considering the adjacent neurological and vascular structures. Another practice is the addition of extra opacifiers (barium sulphate, zirconium dioxide or powdered tungsten) to help with radiological visualisation.4,11,30 These departures from traditional practice may significantly reduce the compressive strength of the resulting cement, the former by reducing polymer chain concentrations and the latter by introducing multiple stress risers.11,31 Care should be taken when performing such unpredictable alterations especially as the mechanical properties of new percutaneous vertebroplasty biomaterials have now been described.29
The performance of cemented THR is strongly supported by both registry figures16,36 and clinical research.35,40,41 This reflects the practice of surgeons in many countries who are comfortable with their cementing technique. The mechanical characteristics of PMMA are key to this success.
Cemented implants have two interfaces, the implant/cement junction and the bone/cement interface, both of which ensure preservation of mechanical stability. Success depends upon the surgical technique, the design of the implant and the properties of the cement. Cemented acetabular components, generally made of ultra high molecular weight polyethylene (UHMWPE) (Young’s modulus of approximately 1 GPa), have a closer stiffness to cement and bone than they do to metal stems. Macro-interlock with cement is achieved using deep grooves in the UHMWPE, and most are overlapped to assist cement pressurisation. Transmitted forces are predominantly compressive with some shear. Charnley38 based the principles of ‘low friction arthroplasty’ on limiting these dangerous shear stresses.
Many
different
philosophies
of
design
have
been
applied
to
cemented
stems.
The
main
differences
between
them
occurs
in the
texture
of
shape
and
surface,
which
determine
the
nature
and
magnitude
of
forces
at the
interfaces
because
of the
way
they
interact
with
cement.
The
survival
of the
bone/cement
interface
governs
the
outcome
of
cemented
THR.
In 1976, Lautenschlager et al45 highlighted the lack of standardisation governing cement and the consequent difficulty in making comparisons between different studies. There are now international standards concerning biomaterials, including bone cements.46 These were updated in 2002, specifying mechanical and working properties for proprietary cements in clinical use. The International Organisation for Standardisation Document (ISO) 5833:200246 tests the working and static strength properties of bone cement under unphysiological laboratory conditions. Cement companies are required to provide a graph of the working properties with each of their packs. However, over 90% of complaints from clinical users indicate that handling in vivo does not match these properties.14
The
principal
problem
with
ISO
and
other
testing
standards
is
concentration
on
short-term
static
strength
properties,
which
are
poor
at
distinguishing
between
different
formulations
of
cement
and
additive.14
The
static
properties
of the
leading
cement
brands
are
summarised
in
Table
II Polymethylmethacrylate has the unique property of continued polymerisation in vivo but this is a prolonged process lasting for between 28 and 70 days.49 The long-term properties of bone cement, including fatigue behaviour, the visco-elastic properties of creep and stress relaxation are central to the success of cemented hip replacement33 and designs that exploit these properties have been clinically validated.36
Creep.
Stress
relaxation. Polymers demonstrate features of both elastic solids and viscous liquids under conditions of low strain and hence are described as visco-elastic. At a molecular level, relatively weak non-covalent bonds exist between adjacent polymer side-chains, and these may be breached, resulting in visco-elastic properties. Mathematical models have been applied to this behaviour.49,50 At the implant level the trend towards polished tapered stem designs has been facilitated by the visco-elastic properties of PMMA. Robust evidence from both finite element analysis and laboratory studies indicates that the subsidence of a stem within the cement mantle by the process of creep protects the vital bone/cement interface and hence the replacement overall.51,52 This is supported by excellent clinical results using such a combination of components.36,41,44 Those who favour shape-closed designs have not exploited visco-elastic behaviour and have indeed taken measures to reduce it by altering the cement.53,54 The visco-elastic behaviour of PMMA is therefore increasingly under investigation. The creep behaviour of leading cement brands can differ significantly even though their static properties are similar.55 In vivo, cement is bathed in water which permeates the PMMA and acts as a plasticiser (internal lubricant). Plasticisers, which include unreacted monomer and lipids, increase the creep of the cement.56,57 The use of co-polymers with high hydrophilicity, such as methacrylate-methylmethacrylate (MAMMA) copolymer in Palacos cement (Heraeus Medical Gmbh, Hanau, Germany), also increases creep.2,58 Polymethylmethacrylate continues to polymerise for weeks after implantation and the creep is higher in this younger cement.49,58 The constraint of the proximal femur has a profound limiting influence on the visco-elastic properties.59 An increased understanding of the effects of additives to cement upon creep is now developing. Antibiotics increase the creep of PMMA and this appears to be related to the porosity of the cement.60 There is much yet to be discovered in this field.
In 1970 Buchholz and Engelbrecht61 incorporated gentamicin in PMMA for the treatment of infection in prosthetic joints. Initially the antibiotic was added by hand, and subsequently during manufacture, making antibiotic-loaded acrylic cement widely available as part of antimicrobial prophylaxis in primary arthroplasty. There is valid evidence to support the prophylactic use of antibiotic-loaded acrylic cement62 which remains standard practice in the United Kingdom, Western Europe and Scandinavia, and is in transition in the USA. In 2003 the Food and Drug Administration63 accepted the use of three commercial antibiotic-loaded acrylic cements in the second stage of revision surgery for prosthetic joint infection. Their use in primary total joint replacement remains unauthorised. The American Academy of Orthopaedic Surgeons has produced guidelines regarding the use of antibiotic-loaded acrylic cement and advises its use as a prophylactic measure only in cases where the patient has significant risk factors for infection.63 The use of antibiotic-loaded acrylic cement in joint replacement provides short- to medium-term protection against prosthetic infection. It aims to overlap with, and then replace, the prophylaxis provided by peri-operative intravenous antibiotics. To achieve this it must be released from cement in high enough concentrations to exceed the minimum inhibitory concentration of potential colonising bacteria. The elution behaviour of acrylic bone cement has been studied extensively.64 Gentamicin is the most common additive because it has, amongst other features, a good spectrum of concentration-dependent bactericidal activity, thermal stability and high water solubility.65,66 In 1980, Wahlig and Dingeldein65 gave robust evidence of gentamicin release from Palacos cement for up to five and a half years in patients who had undergone THR. Following this they collaborated with Buchholz67 in a trial assessing the release of differing concentrations of gentamicin from Palacos cement in patients with a THR. Palacos/gentamicin was established as an ideal antibiotic delivery system.67 Others have confirmed reliable release of gentamicin from Palacos R (Heraeus Medical GMbH) cement (0.5 g per 40 g mix).68 However, concerns about antibiotics in cement still persist: Induction of antibiotic resistance. In 1989 Hope et al69 found that 90% of Staphylococcal strains isolated from infected hip replacements were resistant to gentamicin but if plain cement had been used at the initial operation the rate was only 16%. Other studies have confirmed that antibiotic-loaded acrylic cement reduces infection in total joint replacement at the price of increasing resistance.70,71
Hypersensitivity
and
toxic
side
effects.
Unsuitable
antibiotics.
Prolonged
release
of
antibiotic.
Adverse
effects
on the
mechanical
strength
of
polymethylmethacrylate. There remain a number of deficiencies in the literature regarding the behaviour of antibiotic-loaded acrylic cement. Most mechanical studies have assessed the static short-term mechanical properties. These are less clinically relevant than the fatigue life or visco-elastic properties.57 Single antibiotic additives have usually been the focus of mechanical studies but this trend is now changing as the need for antibiotic combinations becomes recognised as a result of the prevalence of multi-resistant bacteria.79 There is a need for continued research into the effects of single and multiple antibiotic additives upon the static and visco-elastic properties of PMMA. These should be performed, where possible, under standardised conditions and should reflect modern techniques of cement preparations. Polymethylmethacrylate bone cement continues to have numerous uses in orthopaedic practice. Clinicians have acquired understanding of many of its properties through both chance and direct research. Continued research is still needed into its long-term mechanical behaviour58 and its interaction with additives such as antibiotics or radio-opacifiers.
| ||||||||||||||||||||||||||||||||||||||