Gene test can help stave off knee and hip replacement

3 minute read

Identifying those at increased risk of advanced OA means prevention and treatment can start earlier.

Australian researchers have developed a polygenic risk score for knee and hip osteoarthritis that can help identify individuals at greater risk of advanced OA and subsequent knee or hip replacement surgery.

The polygenic risk score (PRS) was validated in a study of over 12,000 people with findings published in Arthritis & Rheumatology.

With 100 independent OA-associated variants across 11 OA phenotypes, the PRSs are based on 10 genetic sequence variants for predicting risk of needing knee replacement surgery and 37 for predicting the risk of hip replacement surgery.

“The way such a genetic risk score could be used is as part of a personalised approach to management of OA,” senior author Professor Flavia Cicuttini of Monash University told Rheumatology Republic.

“This score does not change across a person’s life so it can provide the person early in life with information about their risk of severe OA.

“This means they can consider preventive strategies – including preventing weight gain and the development of obesity, losing weight if this is necessary and maintaining physical activity to optimise joint health – early on in order to reduce this risk,” said Professor Cicuttini.

The aim of the study was to validate the PRSs for knee and hip OA in a cohort independent of those used in studies to a derive the PRSs.

Over 12,000 Australian participants enrolled in the international ASPirin in Reducing Events in the Elderly (ASPREE) trial were included in the analysis. Participants were of European descent, aged at least 70 years old (mean 75 years) and had no significant comorbidities. Detailed information about joint replacements before and during the trial was collected.

Around 12% had at least one knee replacement and almost 11% had at least one hip replacement. Participants with high-risk scores (quintile 5) were 44% more likely to have a knee replacement and 88% more likely to have a hip replacement compared with those who had low-risk scores (quintile 1).

Associations between PRS and risk of hip replacement were higher in women than men, with high-risk women more than twice as likely to have a hip replacement than low-risk, and high-risk men one-and-a-half times more likely than low-risk.

The association between hip PRS and hip replacement was stronger than knee PRS and knee replacement, which the authors suggested reflects the greater genetic component of hip OA and the importance of hip bone shape.

One limitation of the study was the older age group, which while covering the majority of joint replacement recipients limits its applicability to younger patients, and the authors said the genetic influence in younger patients warrants further investigation. The European ethnicity and relatively good health of the study group also potentially affects its applicability to the broader OA population.

In practical terms, Professor Cicuttini suggested one way this genetic risk could be used is in the case of a person having joint pain.

“For example, in the case of knee pain, community-based studies of women 18–55 years old have shown that 1 in 3 at any time report ‘any knee pain’. Such knee pain can be ‘a call to action’ where attention to joint health should be considered…preventing weight gain, exercise.

“These early-stage symptoms could be an opportunity to do the risk score as this additional information on personalised risk may help the individual make decisions on how to prevent and slow their OA,” she said.

Professor Cicuttini said the risk scores also provide the opportunity to identify those who should be considered for new treatments as they develop, and could help identify ‘fast progressors’ to take part in clinical trials.

Arthritis & Rheumatology 2022, online 4 May

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