Based on analysis of the genetic variants associated with developing knee and hip osteoarthritis, researchers can now identify which variants are associated with the risk of requiring surgery. A researcher says that this improves knowledge of knee and hip osteoarthritis, which is necessary to improve diagnosis and develop new treatments.
An estimated 530 million people have osteoarthritis. In Europe, about 7% of the population does.
This debilitating disease affects people differently. Some people experience mild symptoms, and others need hips and knees replaced.
Now researchers have analysed the genetics behind osteoarthritis and have found which genetic variants are associated with an increased risk of requiring surgery for osteoarthritis and how this is linked to other chronic pain conditions.
The research has been published in Annals of the Rheumatic Diseases.
“Knee and hip osteoarthritis has a substantial genetic component, and now we have investigated how genetics affects disease severity. This kind of research improves our understanding of the disease and may point towards opportunities to develop drugs to combat it. It can potentially also be used to detect people with a high genetic risk of severe knee and hip osteoarthritis early so they can receive treatment before it worsens,” explains a researcher behind the study, Cecilie Henkel, physician and PhD Candidate, Department of Orthopaedic Surgery, Copenhagen University Hospital Hvidovre, Copenhagen.
Data on more than 700,000 people
To learn more about the genetics behind the severity of knee and hip osteoarthritis, the researchers used biobank and registry data from Denmark, Iceland and the United Kingdom. They examined data on more than 700,000 people: some had osteoarthritis, and others did not.
Through the registries, the researchers had access to information about these people’s osteoarthritis status and whether they had undergone surgery for knee or hip osteoarthritis and comprehensive analysis of their genetics.
This enabled the researchers to link the individual genetics with the risk of developing knee or hip osteoarthritis and to investigate whether specific genetic variants are associated with a greater risk of osteoarthritis requiring surgery versus not requiring surgery.
“We know that the heritability of osteoarthritis is about 50%, and more than 100 genetic variants that affect the risk have already been identified. But we do not know how and to what extent the individual genetic variants affect the disease trajectory, such as whether the variants cause relatively mild osteoarthritis or severe osteoarthritis requiring surgery,” says Cecilie Henkel.
52 genetic variants associated with increased risk of knee or hip osteoarthritis
The researchers examined the data for 23 million genetic markers to find differences between people with and without knee or hip osteoarthritis and between people with knee or hip osteoarthritis needing and not needing surgery.
The researchers also examined the genetic overlap between knee or hip osteoarthritis and other pain conditions, including back pain and fibromyalgia.
The data showed the following.
- 22,525 people with knee osteoarthritis required surgery.
- 38,626 people with knee osteoarthritis did not require surgery.
- 20,221 people with hip osteoarthritis required surgery.
- 17,847 people with hip osteoarthritis did not require surgery.
In addition, the researchers found that 52 genetic variants were associated with an increased risk of developing knee or hip osteoarthritis. Of these, 18 were associated with an increased risk of developing knee osteoarthritis and 34 with an increased risk of developing hip osteoarthritis.
“These genetic variants all affect the risk slightly, and the more variants one has that are associated with developing knee or hip osteoarthritis, the greater the risk. We also identified 10 genetic variants that have not previously been found to be associated with the risk of developing osteoarthritis,” explains Cecilie Henkel.
41 genetic variants increase the risk of requiring surgery
The researchers found that 41 of the 52 genetic variants were associated with an increased risk of requiring a knee or hip replaced.
“This study is the first to directly compare the genetics of patients on opposite sides of the treatment trajectory of osteoarthritis. The results are interesting because they indicate that some genetic variants are associated with an increased risk of severe osteoarthritis, with people so badly affected that they need surgery. Severe osteoarthritis vastly affects people’s quality of life; they may have difficulty working, pursuing their leisure activities or carrying out daily tasks. And this harms not just the person with osteoarthritis but also society, which has to pay for surgery and sick days,” says Cecilie Henkel.
Inverse association with other pain conditions
In the second part of the study, the researchers found that people with osteoarthritis not requiring surgery versus requiring surgery had greater genetic overlap with pain conditions such as back pain and fibromyalgia.
At first glance, the result seems counterintuitive, but Cecilie Henkel explains that a possible human component may play a role.
“Speculatively, people with a genetic tendency to experience more pain may visit a doctor with milder degrees of osteoarthritis when surgery is not yet relevant. They are thus diagnosed without being offered surgery. Conversely, people with low pain levels or good pain management may not seek health care until their condition has progressed to a state in which surgery is required. We also know that people with fibromyalgia have a greater risk of complications and chronic pain after joint replacement surgery, and surgeons may therefore be more reluctant to operate on them,” explains Cecilie Henkel.
Improved understanding may identify drug targets
Cecilie Henkel says that the study is a first step towards improving our understanding of osteoarthritis as a disease for which there is no optimal treatment.
The results may potentially be useful for assessing people’s risk of severe osteoarthritis, so that preventive measures can potentially be introduced before it becomes so severe that surgery is required.
In addition, the results can also make researchers more aware of the genetic component of osteoarthritis and thereby identify new possible drug targets to curb the disease.
“We need drugs that can change the disease trajectory, and by knowing the genetic variants that make the disease more serious, we can target the development of drugs towards these disease processes. There is still a long way to go, but the potential is great and this is an important first step,” concludes Cecilie Henkel.