A major hurdle to developing treatment for osteoarthritis — other than pain relief medications — is that there has been no way to spot the condition in its earliest stages. Researchers are surmounting this shortcoming with the development of simple blood tests to predict the future risk of knee osteoarthritis progression.
A team led by Duke rheumatologist and research scientist Virginia Byers Kraus, MD, PhD, recently published data on a new test that they describe as “best-in-class” compared with the other research-use-only tests currently available.
Kraus says that traditional measures used to predict osteoarthritis progression — such as age, sex, BMI, and radiographic severity — offer little prognostic value in practice. As a result, researchers cannot differentiate whether joint pain is a transient event or a sign of significant future problems. So clinical trials assessing potential therapies must enroll patients based on evidence of joint damage from radiographs or MRIs — patients whose disease has already progressed.
More than a decade ago, Kraus began looking in synovial fluid and blood for biomarker proteins that could be the earliest harbingers of future disease and disease progression. From the thousands of possibilities, she eventually identified the most promising.
“We found that as few as 11 proteins could predict the risk of knee X-ray worsening over the next two to four years. Only 10 proteins are needed to predict pain worsening. And there is one protein that is of great interest called cartilage acidic protein 1 that predicts both X-ray and pain progression,” Kraus says. “A test will be most useful for clinical trials to determine if a drug is effective for stopping disease progression.”
Kraus is teaming with Duke colleagues to apply this biomarker expertise in an ongoing study of the future risk of osteoarthritis among patients who are undergoing a second ACL repair. The study is looking at markers in synovial fluid, imaging of the knee, and biomechanical effects of how the patients move their knees.
Brian Lau, MD, a sports medicine orthopaedic surgeon collaborating on that study, cites a theory that this injury triggers a cascade of injury. “When the knee swells up after an injury, you develop all these enzymes and cytokines that break down the cartilage,” Lau says. “If you have an ACL injury, should we take the fluid off as quickly as possible to prevent that material from breaking down the cartilage? Part of the study is trying to understand what happens, and if we can prevent the damage.”
Kraus questions the generally accepted belief that “osteoarthritis is a normal accompaniment of aging, a wear-and-tear disease that is an inevitable part of life.” She believes that recognizing the disease in its earliest stages is the first step identifying the mechanisms that cause damage — a prerequisite to finding ways to prevent or treat it.