New bone cement formulations with reduced side effects are being studied at the University of the Basque Country. Traditional use of such adhesives, based on on polymethylmetacrylate polymers, (PMMA, also known by the trade names Plexiglas, Perspex and Lucite) has been setting of the prothesis inside bone during hip replacements. A newer usage of these acrylic cements is in a new technique known as vertebroplasty.
Vertebroplasty is mostly applied in treating vertebral fractures caused by osteoporosis or bone tumors. The goal is to reinforce the bone and alleviate pain.
The technique is minimally invasive and quick, taking 40 minutes per vertebra, and efficacious in alleviating pain, due to the mechanical reinforcement provided by the cement. The cement, in vertebroplasty, is injected into the affected vertebra via long narrow needles, and can be visualized with X-rays.
A 1998 study reported 80 patients showed complete relief of pain in over 90 percent of osteoporosis cases. A follow-up of these patients population also showed evidence of extended pain relief.
However, risk of migration of the cement and of bone necrosis has to be taken into account. PMMA for orthopedic application is supplied as a powder with liquid methyl methacrylate (MMA). When mixed these become a dough-like cement that gradually hardens, and in doing so, releases heat of quite a high temperature, killing the bone in the surrounding area.
Additionally, even though PMMA is biologically compatible, MMA is considered to be an irritant and a possible carcinogen. PMMA has also been linked to cardiopulmonary events in the operating room due to hypotension.
Researchers at the Department of Polymer Science and Technology at the University of the Basque Country focused on these issues in this study. What with the recent news on the effect of oral bisphosphonates such as Fosamax on bone necrosis, this is good timing.
Old and New Formula Applications
The formula used for the vertebroplasty cement consists chiefly of the MMA monomer, PMMA pearls and a radiopaque agent. The last ingredient is what enables visualisation of the cement bulk during the injection .
These formulas must work within the following constraints: appropriate viscosity and high radiopacity. The cement must have a certain consistency so as not to drip, and sufficient fluidity to be injected, as well as being highly visual with X rays, so that the surgeon can see what is being injected.
To be able to adapt the basic formula to new applications, surgeons typically modify the cements when operating. In order to ease the injection, they either add more monomer in liquid to reduce the viscosity and increase working time or, otherwise, increasing their visibility for the X rays by the addition of more radiopaque agents. All these changes in turn affect the properties of the cement and its toxicity.
Scientists at the Department of Polymer Science and Technology at the UPV/EHU are trying to develop new formula for acrylic bone cements designed specifically for injectable use and which provide what could possibly be an additional therapeutic action.
The researchers have observed that it is possible to obtain injectable bone cements with rheological properties and with suitable selection of PMMA pearl particle size. The greater the size of the pearls, the heat produced during polymerisation is dissipated more, and less heat is produced in the polymerisation reaction, thus producing a greater heating of the tissue.
Once the PMMA pearl particle size is selected, radiopaque and/or therapeutic agents are incorporated into the formula. These can intervene in the process of curing and quantify the effects produced in the properties of the cement.
On the one hand, bismuth salicylate has been added, combining the analgesic effects of salycilic acid with that of the bismuth, a metal easily visible using X rays. Thus, the results reflect a suitable radiopacity provided by the bismuth, a therapeutic effect of the salycilate and less toxicity and good compatibility overall.
Also, acrylic cements are formulated by adding bioactive elements, the idea being to obtain the interaction between the cement and the biological tissue, in some way causing the fixing of the tissue (osteoregeneration). In fact, strontium hydroxiapatite has been incorporated in order to combine the visibility of strontium and the immediate fixing of acrylic cement with the long-term fixing of the bioactive ingredient.
Lastly, in collaboration with other research centers, the EHU-UPV researchers did in vitro and in vivo biocompatibility studies. The studies undertaken to date have not given any more problems than cements with traditional commercial formula.
1.Cotten A, Boutry N, Cortet B et al. (1998), Percutaneous vertebroplasty: state of the art. Radiographics 18(2):311-320
2. Deramond H, Depriester C, Galibert P, Le Gars D (1998) Percutaneous vertebroplasty with polymethylmethacrylate Technique, indications, and results. Radiol Clin North Am 36(3):533-546.
3. American Journal of Neuroradiology, 23:601-604, April 2002.
4. Gangi A, Kastler BA, Dietemann JL (1994), Percutaneous vertebroplasty guided by a combination of CT and fluoroscopy. AJNR Am J Neuroradiol 15(1):83-86
Image:X-ray of hip replacement prosthesis- Wellcome Images Library./ Creative Commons License
Photo: Manfred Kielnhofer CC BY-SA
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