VERTEBROPLASTY:

PMMA bone cements
(author: Thammo Weise)

PMMA-based bone cement has been successfully used in endoprosthetics and dental surgery for over 40 years now. The plastic polymethyl methacrylate (PMMA) was developed back in 1902 by the chemist Otto Röhm and has since been known as Perspex®. Its excellent biocompatibility was ascertained indirectly in the Second World War. The cockpit roofs of many aircraft were made of PMMA, as it was far easier to shape than glass. Pilots who had crashed and survived and were operated many years later revealed Perspex splinters which had indeed penetrated the skin but had left no rejection reactions whatsoever thus demonstrating basic human acceptance.

PMMA-based bone cements for vertebroplasty consist of two components: The polymer powder consisting of 60-70% polymethyl methacrylate, 0.4-0.6% initiator (benzoyl peroxide), 25-45% X-ray contrast agent (barium sulphate or zirconium oxide) and additional components, such as dyes, plasticisers or calcium phosphate compounds (hydroxyapatite). The liquid monomer comprises 90-97% methacrylate (MMA), 0.2-0.25% activator and additives, such as dyes, inhibitors and stabilisers*. Mixing the two components triggers a redox reaction through the initiator, which generates free radicals. These radicals allow the MMA to bind to the powder PMMA thereby initiating the formation of extremely long-chain polymers. Additives, such as inhibitors, serve to control the rate of the polymerisation process; plasticisers keep the implant elastic within limits.

During hardening a reaction heat of 57 kJ/mol is liberated, which causes an increase in temperature to 40-46°C in the boundary layer between the implant and the spongiosa. Loosening and therefore inflammation can arise in orthopaedics as a consequence of this primary damage, however, in vertebroplasty the heat is attributed an analgesic effect. Polymerisation shrinkage also takes place during the course of the reaction, which, depending on cell porosity, may amount to around 6-7% and is therefore lower in manually mixed cements than in vacuum-mixed cements. The reasons for the volume reduction are the physical shrinkage of the cement on cooling, but also the 2-6% of monomer gases released, which are not bound by the reaction. As the gases are toxic to cells, it is assumed that nociceptive nerve endings in the periosteum are damaged and this also contributes to a reduction in pain. Animal studies show that the substances used for X-ray opacity have an osteolytic effect on the bone, whereby the effect is more extreme with barium sulphate than with zirconium oxide. This effect can be reduced by lowering the proportions in the powder, although the Xray contrast also declines. An alternative is the addition of hydroxyapatite, a bone-like calcium phosphate compound that not only improves the osteoactivity of the implant thereby reducing the risk of inflammation, but is also X-ray opaque.

Studies of persons working in areas exposed to monomer gas have shown that the reactions are diverse and it is therefore hard to generalise. Two areas are generally distinguished – those where there is exposure to a certain monomer concentration over a prolonged period and those in which very high exposures can exist for a short period, as in the clinical case. Occupational health and safety guidelines take the view that no more than 100 ppm MMA should be present in the air breathed for a brief period and no more than 50 ppm MMA over a period of 8 hours. Nevertheless, diverse reactions are described for all the occupational groups subject to exposure, whose occurrence is not unequivocally attributable to the effect of MMA. These effects can be manifested as skin irritation, impairment of the sense of smell, an eczema-like rash and inflammation of the nasal mucus membrane through to asthma, chronic bronchitis and migraine headaches. Similar research results have been sought for carcinogenicity and genotoxicity, but no definitive conclusions can be drawn here either.

The data available demonstrates, however, that a health hazard may be assumed from monomer gases in breathing air. Consequently, there is also an increasing tendency in clinical practice to reconsider mixing PMMA-based cements. In the long term the use of a closed mixing system will become standard. As well as the significantly improved mixing results - in terms of inhomogeneous mixing of components, mechanical properties and reproducibility of the cement - the minimisation of monomer gas exposure was another decisive reason for SOMATEX® to establish the SOMIX® mixing system on the market as early as 2004 and to expand its product portfolio for vertebroplasty.

Sincerely yours, Thammo Weise

*The volume specifications refer to the quantities related to the individual components and not to the ready mixed cement. The composition, ratios of contents and particularly the additives can vary considerably between manufacturers.