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How Scientists Tackle Chronic Osteomyelitis using Bioactive Glass

October 10, 2022

If you asked doctors how to treat chronic osteomyelitis, they would likely all say the same thing: antibiotics, amputation, or bone grafts. However, if you asked the scientists at Galeazzi Orthopedic Institute, you might get told that the best way to treat chronic osteomyelitis is with bioactive glass S53P4, one of the most recent and promising medical advancements for bone treatment. But what makes bioactive glass S53P4 so special? 

First off, we need to understand what osteomyelitis is, and subsequently what chronic osteomyelitis is. Osteomyelitis is an infection of the bone tissue which can occur due to bone damage, surrounding soft tissue damage, or nearby surgery which allows pathogens to penetrate the protective outer layer of the bone. Once within the bone, pathogens can cause varying degrees of bone loss as the infection progresses. Ultimately, this bone loss can result in limb amputation, sepsis, or even death as a progressed infection can result in organ failure. 

As mentioned above, the traditional treatments for osteomyelitis consist of antibiotics to kill the responsible pathogen and stop the spread of the infection; however, antibiotics are not always the best option as they can affect other microorganisms in the body. Furthermore, overuse of antibiotics in a clinical setting has allowed for the development of antibiotic resistant pathogens, such as methicillin resistant staphylococcus aureus (MRSA), which will eventually render antibiotics useless. Furthermore, higher degrees of bone loss can result in a very weak bone which cannot be treated with antibiotics alone. So, what are our other options? 

Figure 1: Xray of a knee with osteomyelitis, as highlighted in red.

Clinically, if you want to avoid losing a limb, the next best options would be antibiotic loaded polymethylmethacrylate beads (PMMA) or bone grafting. Both of these methods work through the surgical removal of the necrotic bone tissue and the replacement of that bone tissue with PMMA or fresh bone from a graft.

Visual depiction of PMMA in bone
Figure 2: Xray of PMMA that is packed into the tibia of a patient after the removal of necrotic bone from osteomyelitis.

 

However, there are some drawbacks as these methods are only designed to fill the bone cavity left behind from the infection, provide limited local antibiotics, and take a long time to produce results. Sadly, bone doesn’t grow overnight! So, what if there was something that could fill the bone cavity, stimulate bone growth, and was naturally antibiotic resistant?

Enter bioactive glass S53P4 (BAG S53P4). Bioactive glass itself is a silica based biodegradable glass which has been shown to have antibiotic, osteoconductive, and angiogenic properties. Which is essentially a way of saying it stimulates bone growth and blood vessel growth all while repelling those pesky pathogens! BAG S53P4 takes it a step further and is composed of SiO2, Na2O, CaO, and P2O5 which further stimulates bone growth by chemically binding to surrounding bone. This almost sounds too good to be true, so researchers at Galeazzi Orthopedic Institute set out to understand how BAG S53P4 is so effective and determine its safety in a clinical setting. 

To determine the source of BAG S53P4s antibiotic properties and to evaluate its safety, the research team took 27 patients with chronic long bone osteomyelitis from antibiotic resistant pathogens and treated them using the bioactive glass.  From their study, they were able to determine that the antibiotic resistant properties of BAG S53P4 stems from its contact with an aqueous solution. By contacting an aqueous solution, BAG S53P4 activates the release of ions which increase the surrounding pH. This increased pH creates a hostile environment for bacterial growth stopping infection in its tracks. As a result, 90% of the treated patients showed no signs of infection after 18 months. X Rays of the patient treated with BAG S53P4 were also taken over the course of 18 months. From these X Rays, the team was able to determine that the vascularization and bone growth seen in these patients far surpassed that of previous methods and was equally safe in its application. 

Figure 3: Before and after Xray’s of a patient treated with BAG S53P4 over the course of 2 years for chronic osteomyelitis.

Ultimately, this research determined that BAG S53P4 was a safe and effective treatment for patients suffering from chronic osteomyelitis. So next time you’re asked how to treat chronic osteomyelitis, consider the less traditional route and give BAG S53P4 a try!  

Source:

Drago, L., Romanò, D., De Vecchi, E., Vassena, C., Logoluso, N., Mattina, R., & Romanò, C. L. (2013). Bioactive glass BAG-S53P4 for the adjunctive treatment of chronic osteomyelitis of the long bones: An in vitro and prospective clinical study. BMC Infectious Diseases, 13(1), 1-8.

https://pubmed.ncbi.nlm.nih.gov/24325278/

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About Author

As a GT undergrade in biology and medical scribe, Jamesie has a passion for medicine and understanding the physiological and underlying mechanisms behind our favorite diseases.

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  Timothy Durham was convicted of rape when a test showed his DNA genotype matched the DNA recovered from the crime scene. Eye witnesses testified that Durham was in a different state at the time of the incident, but he wasn’t exonerated from his 3000 year sentence until follow up DNA analysis showed that the preliminary forensic analysis used in the trial was misinterpreted (Thomas et al.). DNA testing serves an invaluable part in our criminal justice system, but it comes with complications and bias that can lead to wrongful convictions and misinformed juries.  

Background:

Forensic genetics aims to identify the origin of a biological sample. It can be traced back to Karl Landsteiner who discovered human ABO blood groups. With blood groups, suspects could be eliminated based on their blood type. For example, if a suspect had type A blood and there was type B blood left at the scene by the perpetrator, the investigators could rule out the suspect. Unfortunately, the reverse didn’t work. If the suspect and perpetrator both had the same blood type, it can’t be concluded that the suspect was guilty. Blood identifiers evolved into 8 distinct categories which improved the ability to eliminate suspects, but could only conclude that (if the system matched) it might be the perpetrator or this person might be related to the perpetrator (Jobling and Gill). The field evolved in the 1980s with the discovery of Minisatellites, lines of repetitive DNA that don’t encode proteins. Minisatellite patterns in DNA create what we know today as the DNA fingerprint, and it has a much higher accuracy rate than previous methods (Augustyn et al.). Around the same time, a breakthrough for victims of sexual assault was discovered. In the case of assault, bodily fluids of both the victim and the assaulter can get mixed. A process called differential lysis was created which could selectively increase the concentration of sperm in a fluid sample thereby allowing for accurate DNA testing (Jobling and Gill). Forensics evolved to use single-locus probe testing after several years because of its ease of interpretation. It looked at specific minisatellites that had high variability between subjects. This was the first DNA-based method to be used in a criminal investigation. Two murder homicides from several years apart were connected using DNA evidence. The evidence was then used to exonerate an innocent man, and the guilty party was found when he tried to evade mandatory DNA testing for all men in the small town. His guilt was then reinforced when the DNA profiles matched, and he gave a confession (Jobling and Gill). Finding DNA at a crime scene doesn’t guarantee that you’ll find a murderer. There are issues with non-pure samples and limited samples that make DNA work difficult, and accreditation of facilities and new techniques and take time (Jobling and Gill).  

Subjectivity of DNA Interpretation:

In a 2009 publication, the National Academy of Science discusses the possibility for subjective influence in lab based forensics. The interpretation bias happens in complex cases where, for example, there could be a mixture of DNA. A study published in 2011 looked specifically at this issue. A gang rape happened in Georgia, and the mixture in DNA from the case was used to prosecute one suspect after another suspect took a plea bargain to testify against him. With DNA mixtures, there are three possible conclusions: suspect excluded, suspect cannot be excluded, and inconclusive. If the suspect is excluded, it means that there’s little to no possibility that his DNA is part of the sample. If the suspect cannot be excluded, it means that there’s a possibility that his DNA is part of the sample. In the trial, the DNA examiners who knew the context of the case concluded that the suspect being prosecuted could not be excluded. The 2011 study gave the DNA evidence from this case and the DNA profiles of the suspects to 17 forensic examiners. These examiners had no context of the case, and they all worked independently. Of the 17, only 1 came to the same conclusion (suspect cannot be excluded) as the examiners who knew the context of the case. Twelve of the 17 concluded that the suspect who was prosecuted and convicted had no relation to the DNA found in the sample. Not only does this show that subjectivity occurs due to the context of the case, but the 17 examiners came up with different findings based on their past experiences meaning that not all DNA analysis is objective. Some organizations like the Scientific Working Group on DNA Analysis Methods say that quantitative statistical evidence should be presented with every categorical conclusion, but the US doesn’t require this (Dror and Hampikian).

False Positives:

There are two categories that cause wrongful identification in a DNA report: coincidental matches and false positives. Coincidental matches are DNA matches between two unrelated people. The probability of these matches is about 1 to 500,000 for white individuals and about 1 to 350,000 for black individuals. This small probability of coincidental matches makes people feel confident in DNA evidence. False positives, on the other hand, are matches between DNA and test DNA that result from issues in the forensics lab. There have been multiple cases of forensics labs accidentally switching victim and suspected rapist DNA which lead to convictions that were later overturned when the lab realized the error. There are also cases of misreading or misunderstanding a sample. In a case from 1993, a man was convicted of rape because someone interpreted a mixed sample of victim and perpetrator DNA as an individual sample. The conviction was again overturned. To prevent false convictions, retesting DNA is allowed, but it’s not an efficient solution. Many people are pushing for statistical information on the probability of false positives, so that the jurors can make accurate judgements based on DNA evidence (Thomas et al.).  

Conclusion:

DNA analysis is a useful tool for the criminal justice system, but subjectivity can be an issue in forensic testing. To combat wrongful convictions, there are organizations like The Innocence Project who use DNA testing to free the innocent, but reformed forensic testing standards should be put in place to prevent subjectivity and to ensure juries are correctly informed during trials. https://www.innocenceproject.org/    

Citation:

Augustyn , Adam, et al. “DNA Finerprinting.” Encyclopedia Britannica , 26 Apr. 2018, www.britannica.com/science/DNA-fingerprinting#ref153186. Dror, Itiel E., and Greg Hampikian. “Subjectivity and Bias in Forensic DNA Mixture Interpretation.” Science & Justice, vol. 51, no. 4, 2011, pp. 204–208., doi:10.1016/j.scijus.2011.08.004. Jobling, Mark A., and Peter Gill. “Encoded Evidence: DNA in Forensic Analysis.” Nature Reviews: Genetics, vol. 5, no. 10, Oct. 2004, pp. 739–751., doi:10.1038/nrg1455. Thompson, William C, et al. “How the Probability of a False Positive Affects the Value of DNA Evidence.” Journal of Forensic Sciences, vol. 48, no. 1, Jan. 2003, pp. 1–8., doi:10.1520/jfs2001171.