Our Trust has been part of a successful international research study – discovering a genetic link to explain why some patients develop pain and early joint replacement failures.
In a world first, the research, involving our surgical team, could transform the way orthopaedic surgery is carried out globally.
The finding follows over 14 years of research into joint failure led by Dr David Langton, managing director at ExplantLab. David has worked closely with the Trust.
The discovery was published by ExplantLab in leading biomedical research journal, Nature Comms Medicine on 24 June. And it could transform surgery, making it routine for patients to undergo genetic testing before having medical implants.
Tony Nargol, consultant orthopaedic surgeon at the Trust, said: “This exciting discovery comes as a result of the close working relationship our fantastic staff have had with Mr Langton and his team, as well as health staff from organisations across the world.
“This work will help provide a practical way for health professionals to help patients in selecting the best type of implants for their individual bodies. It will mean better outcomes for our patients and could transform the quality of care we provide to our patients.”
What causes joint replacement failure?
Currently, around 10% of the population in the UK will have a joint surgically replaced in their lifetime. This is a proven way to treat joint ailments such as arthritis.
But as populations around the world grow older and heavier, this is leading to more joint replacement being performed. Some five million surgeries are carried out across the world each year. And this number which is forecast to double over the next two decades.
Whilst the majority of patients are satisfied with the results of their surgery, a significant number of joint replacements fail early following adverse immune responses. This can lead to potentially dangerous and costly repeat surgery.
Recognising that longer lasting joint replacements are required, billions of pounds are spent by medical implant manufacturers, to improve implant design, implant materials and to optimise implant alignment using robotic technology.
One of the most popular implant materials used in the majority of joint replacements globally is cobalt chrome (CoCr).
When small particulates from CoCr joints are released into the blood, it can result in pain and joint failure in some people.
Dr Langton, a qualified surgeon with a PhD in immune responses to implants, explains: “A large percentage of joint failures are due to adverse immune responses, where small particles from the joint implant are released into the blood through wear and tear, stimulating an immune response in the body.
“Essentially, the immune system attacks the implant in a process similar to how a patient rejects an organ transplant. How quickly this “sensitisation” happens is variable and unpredictable, but it appears to be dependent on the type of material, the amount of wear debris released and other patient specific factors.”
However, the reasons why some patients reacted so differently to CoCr had proved elusive – until now.
Dr Langton wanted to better understand this. He began to research specific failed joints, the materials they were made from, and how they were being implanted.
Following 14 years of extensive international research, he and his team at ExplantLab, have established a “risk” genotype which places some patients at greater risk of developing CoCr metal sensitivity.
He continued: “Through our research we have been able to demonstrate that a significant percentage of patients carry a genotype that makes it more likely for them to have a reaction to a joint replacement made of a CoCr component(s).”
The ground-breaking study published in Nature Medicine, represents a major step forward in understanding patient-specific responses to CoCr, which is used in around 70% of orthopaedic joints implanted throughout the world.
Orthotype
Taking the research one step further, ExplantLab has worked in collaboration with a number of organisations to develop a machine learning algorithm called Orthotype. This uses a patient’s genotype to provide a risk profile of that patient developing hypersensitivity to CoCr.
Those involved in the development are bioengineers, medical staff and patients from:
- University Hospital of North Tees
- Newcastle University
- Hospital for Special Surgery, New York
- Royal Perth Hospital, Australia
The patented software developed by ExplantLab, uses an algorithm which was developed and validated from the results from 606 patients implanted with metal on metal hip replacements and resurfacings. Each of these patients had been followed for a mean duration of ten years.
Using Orthotype to identify patients and understand the risks prior to surgery, represents a significant advance in orthopaedic care for patients, and a step-change for orthopaedic surgeons. It has potentially significant repercussions for global healthcare systems through the avoidance of repeat surgery.
Not only this, Dr Langton believes the algorithm will be invaluable in the investigation of patients who complain of joint pain after other obvious causes, such as infection, have been ruled out.
Orthotype can be used before or after joint replacement surgery. If used prior to surgery, it can help to guide surgeons in their selection of implant, based on the manufactured material most suited to the individual patient.
Post-operatively, it can be used in conjunction with the measurement of cobalt and chromium concentrations, to allow clinicians to accurately determine a clinical prognosis.
Concluding, Dr Langton said: “We are very grateful to the patients who gave their time, and our academic partners (Newcastle University, University Hospital of North Tees, Hospital for Special Surgery, New York and the Centre for Implant Retrieval Analysis in Perth, Australia. Tees, Perth, HSS NYC) and Arthroplasty for Arthritis who that contributed their hard work and expertise to this research.
Orthotype has since been registered with the MHRA for use in the United Kingdom.
ExplantLab accessed the same technological and statistical expertise for the study which saw them produce award-winning research into COVID-19.
Working with Newcastle University as well as Northumbria Healthcare, Newcastle Hospitals Trust and University of Oslo, ExplantLab was also the first to describe a gene which confers protection against severe complications of COVID: HLA-DRB1*04:01.
Dr Langton added: “Interestingly, the frequency of this particular gene strongly correlated with a population’s latitude, potentially providing some understanding of the global variation in the impact of the disease.”
The paper was given an award at the recent European Federation of Immunogenetics and Histocompatibility Annual Meeting.
