Blood Biomarkers Predict Knee Osteoarthritis Years in Advance

A small number of blood biomarkers can identify patients who will develop knee osteoarthritis (OA) up to 8 years before signs of the disease are detectable via X-ray, according to new research.

The study “provides more evidence for a pre-radiographic phase of disease,” wrote Virginia Byers Dr. Kraus, MD, PhD, a professor of medicine, pathology, and orthopedic surgery at Duke University School of Medicine in Durham, North Carolina, and colleagues. The results also “provide valuable information for understanding the molecular events of early disease that could inform strategies to develop disease-modifying drugs for preclinical OA,” they continued.

In the study, published in Science Advances, researchers analyzed blood samples from a population-based, longitudinal study of women in London that assessed participants annually for osteoporosis and OA. They selected individuals at low risk for radiographic knee OA, who did not have traditional risk factors for knee OA such as a history of major knee injury, knee surgery, or OA of the hand or opposite knee.

The researchers analyzed serum of 100 women who went on to develop radiographic knee OA and 100 controls who were matched by age and body mass index (BMI). Participants were, on average, aged 54 years with a BMI of 26 and all were White. They analyzed serum peptides via mass spectrometry and used machine learning to select which out of the 115 identified peptides were most predictive of OA. 

Ultimately, the team zeroed in on six peptides, corresponding to six proteins, that could most accurately distinguish women who went on to develop radiographic signs of OA from controls (area under the receiver operating characteristic curve, 0.77) up to 8 years before x-rays detected these changes. 

“The value of our study is a panel that, in the absence of clinical factors indicative of high-risk knee OA, has the potential to discriminate individuals at risk for incident radiographic knee OA from those not at risk,” the authors wrote.

In earlier work, a similar group of biomarkers could accurately diagnose knee OA as well as predict the progression of the disease. More than half (58%) of biomarkers that predicted incident OA also predicted OA progression.

“Even for the ones that didn’t overlap with OA progression, they all pointed to the same sort of disease process, which is an unresolved acute phase response type of biological process,” Dr. Kraus told this news organization. 

Commenting on the study, Andrew Grose, MD, an orthopedic trauma surgeon at the Hospital for Special Surgery in New York City, noted that the methods and conclusions seemed sound but cautioned that the study only looked for radiographic evidence of OA, and not symptomatic OA. 

“Clinically relevant OA is correlated with what you see on an x-ray, but the x-ray is definitely not the whole story,” he said in an interview with this news organization.

To be clinically relevant, patients must also have symptoms, such as pain and stiffness, and interfere with daily life. But what shows up on an x-ray is not necessarily indicative of what patients are experiencing, he said. Solely focusing on radiographic findings could lead to overdiagnosis and overtreatment of OA, he said.

The study population was also small, and only included White women, he added, so further validation is necessary. Dr. Kraus and colleagues also acknowledged these limitations.

“Further validation will be needed in independent and larger cohorts, preferability prospectively collected and including male participants and the combination of incident radiographic and symptomatic OA,” they wrote. They noted that while this current study included only women, the biomarkers were not associated with sex in previous studies that used larger and mixed-sex cohorts.

“If they did more studies showing that this [test] was able to predict clinically relevant OA, then I think you could have a meaningful conversation with a patient in a primary care doctor’s office,” Dr. Grose added. “Until that time, just the fact that it predicts an x-ray finding is a little bit of a red herring.”

This work was supported by grants from the National Institutes of Health. Dr. Kraus is an inventor on a patent related to OA progression biomarkers. Dr. Grose had no relevant disclosures. 

A version of this article appeared on Medscape.com.

A small number of blood biomarkers can identify patients who will develop knee osteoarthritis (OA) up to 8 years before signs of the disease are detectable via X-ray, according to new research.

The study “provides more evidence for a pre-radiographic phase of disease,” wrote Virginia Byers Dr. Kraus, MD, PhD, a professor of medicine, pathology, and orthopedic surgery at Duke University School of Medicine in Durham, North Carolina, and colleagues. The results also “provide valuable information for understanding the molecular events of early disease that could inform strategies to develop disease-modifying drugs for preclinical OA,” they continued.

In the study, published in Science Advances, researchers analyzed blood samples from a population-based, longitudinal study of women in London that assessed participants annually for osteoporosis and OA. They selected individuals at low risk for radiographic knee OA, who did not have traditional risk factors for knee OA such as a history of major knee injury, knee surgery, or OA of the hand or opposite knee.

The researchers analyzed serum of 100 women who went on to develop radiographic knee OA and 100 controls who were matched by age and body mass index (BMI). Participants were, on average, aged 54 years with a BMI of 26 and all were White. They analyzed serum peptides via mass spectrometry and used machine learning to select which out of the 115 identified peptides were most predictive of OA. 

Ultimately, the team zeroed in on six peptides, corresponding to six proteins, that could most accurately distinguish women who went on to develop radiographic signs of OA from controls (area under the receiver operating characteristic curve, 0.77) up to 8 years before x-rays detected these changes. 

“The value of our study is a panel that, in the absence of clinical factors indicative of high-risk knee OA, has the potential to discriminate individuals at risk for incident radiographic knee OA from those not at risk,” the authors wrote.

In earlier work, a similar group of biomarkers could accurately diagnose knee OA as well as predict the progression of the disease. More than half (58%) of biomarkers that predicted incident OA also predicted OA progression.

“Even for the ones that didn’t overlap with OA progression, they all pointed to the same sort of disease process, which is an unresolved acute phase response type of biological process,” Dr. Kraus told this news organization. 

Commenting on the study, Andrew Grose, MD, an orthopedic trauma surgeon at the Hospital for Special Surgery in New York City, noted that the methods and conclusions seemed sound but cautioned that the study only looked for radiographic evidence of OA, and not symptomatic OA. 

“Clinically relevant OA is correlated with what you see on an x-ray, but the x-ray is definitely not the whole story,” he said in an interview with this news organization.

To be clinically relevant, patients must also have symptoms, such as pain and stiffness, and interfere with daily life. But what shows up on an x-ray is not necessarily indicative of what patients are experiencing, he said. Solely focusing on radiographic findings could lead to overdiagnosis and overtreatment of OA, he said.

The study population was also small, and only included White women, he added, so further validation is necessary. Dr. Kraus and colleagues also acknowledged these limitations.

“Further validation will be needed in independent and larger cohorts, preferability prospectively collected and including male participants and the combination of incident radiographic and symptomatic OA,” they wrote. They noted that while this current study included only women, the biomarkers were not associated with sex in previous studies that used larger and mixed-sex cohorts.

“If they did more studies showing that this [test] was able to predict clinically relevant OA, then I think you could have a meaningful conversation with a patient in a primary care doctor’s office,” Dr. Grose added. “Until that time, just the fact that it predicts an x-ray finding is a little bit of a red herring.”

This work was supported by grants from the National Institutes of Health. Dr. Kraus is an inventor on a patent related to OA progression biomarkers. Dr. Grose had no relevant disclosures. 

A version of this article appeared on Medscape.com.

A small number of blood biomarkers can identify patients who will develop knee osteoarthritis (OA) up to 8 years before signs of the disease are detectable via X-ray, according to new research.

The study “provides more evidence for a pre-radiographic phase of disease,” wrote Virginia Byers Dr. Kraus, MD, PhD, a professor of medicine, pathology, and orthopedic surgery at Duke University School of Medicine in Durham, North Carolina, and colleagues. The results also “provide valuable information for understanding the molecular events of early disease that could inform strategies to develop disease-modifying drugs for preclinical OA,” they continued.

In the study, published in Science Advances, researchers analyzed blood samples from a population-based, longitudinal study of women in London that assessed participants annually for osteoporosis and OA. They selected individuals at low risk for radiographic knee OA, who did not have traditional risk factors for knee OA such as a history of major knee injury, knee surgery, or OA of the hand or opposite knee.

The researchers analyzed serum of 100 women who went on to develop radiographic knee OA and 100 controls who were matched by age and body mass index (BMI). Participants were, on average, aged 54 years with a BMI of 26 and all were White. They analyzed serum peptides via mass spectrometry and used machine learning to select which out of the 115 identified peptides were most predictive of OA. 

Ultimately, the team zeroed in on six peptides, corresponding to six proteins, that could most accurately distinguish women who went on to develop radiographic signs of OA from controls (area under the receiver operating characteristic curve, 0.77) up to 8 years before x-rays detected these changes. 

“The value of our study is a panel that, in the absence of clinical factors indicative of high-risk knee OA, has the potential to discriminate individuals at risk for incident radiographic knee OA from those not at risk,” the authors wrote.

In earlier work, a similar group of biomarkers could accurately diagnose knee OA as well as predict the progression of the disease. More than half (58%) of biomarkers that predicted incident OA also predicted OA progression.

“Even for the ones that didn’t overlap with OA progression, they all pointed to the same sort of disease process, which is an unresolved acute phase response type of biological process,” Dr. Kraus told this news organization. 

Commenting on the study, Andrew Grose, MD, an orthopedic trauma surgeon at the Hospital for Special Surgery in New York City, noted that the methods and conclusions seemed sound but cautioned that the study only looked for radiographic evidence of OA, and not symptomatic OA. 

“Clinically relevant OA is correlated with what you see on an x-ray, but the x-ray is definitely not the whole story,” he said in an interview with this news organization.

To be clinically relevant, patients must also have symptoms, such as pain and stiffness, and interfere with daily life. But what shows up on an x-ray is not necessarily indicative of what patients are experiencing, he said. Solely focusing on radiographic findings could lead to overdiagnosis and overtreatment of OA, he said.

The study population was also small, and only included White women, he added, so further validation is necessary. Dr. Kraus and colleagues also acknowledged these limitations.

“Further validation will be needed in independent and larger cohorts, preferability prospectively collected and including male participants and the combination of incident radiographic and symptomatic OA,” they wrote. They noted that while this current study included only women, the biomarkers were not associated with sex in previous studies that used larger and mixed-sex cohorts.

“If they did more studies showing that this [test] was able to predict clinically relevant OA, then I think you could have a meaningful conversation with a patient in a primary care doctor’s office,” Dr. Grose added. “Until that time, just the fact that it predicts an x-ray finding is a little bit of a red herring.”

This work was supported by grants from the National Institutes of Health. Dr. Kraus is an inventor on a patent related to OA progression biomarkers. Dr. Grose had no relevant disclosures. 

A version of this article appeared on Medscape.com.