In this month’s Q&A column, the panelists discuss the potential of genetic research and how it may lead to new treatment options for osteoarthritis (OA). They also speculate about the possibilities of biologic therapy in the treatment of OA and review their clinical experiences with the use of ultrasound in facilitating appropriate treatment.

Q: How do you think genetic research will impact breakthroughs in the diagnosis and treatment of OA?
A: The panelists agree that genetic research offers promise in facilitating a better understanding of the disease and possibly identifying those who are at a higher risk for developing OA.

There is an increased recognition of the complex, heterogenous nature of OA genetic susceptibility, according to Ara Dikranian, MD. He says genetic polymorphisms that affect knee OA vary between the sexes. However, he notes that variants of the frizzle-related protein (FRZB) gene may have an effect in OA development in multiple joints with a specific, severe involvement of the hip among women.¹

In regard to genetic polymorphisms, Dr. Dikranian says there may be a role for asporin (ASPN), serum cartilage oligomeric matrix protein (COMP), FRZB and the COL2A1 gene when it comes to knee OA among Caucasians. He adds that researchers have recently reported a compelling genetic association with OA of two functional alleles in the asporin gene in a Japanese population. However, other researchers have not found this to be a major influence on OA etiology in a Caucasian population in the United Kingdom, according to Dr. Dikranian.

More specifically, Dr. Dikranian notes that researchers have repeatedly shown that COMP levels correlate with OA symptoms, radiographic severity and progression. Similarly, he says studies have demonstrated correlation in regard to synovial fluid dermatan sulfate and aggrecan levels with knee injury and OA severity.² However, Dr. Dikranian says further research is needed.

“The role of COMP and other biomechanical markers in OA pathogenesis and their potential use in monitoring therapeutic response remains unclear,” notes Dr. Dikranian.

Puja Chitkara, MD, says ongoing clinical research in twin and non-twin studies, genome-wide scanning and population studies show genetic predispositions in some OA patient subsets. She adds that studies have shown a 40 to 65 percent higher risk of hand and knee OA, and a 70 percent higher risk of spine OA.^3,4

Dr. Chitkara notes that researchers have implicated certain genetic mutations such as mutations in collagen genes and extracellular matrix protein genes. She adds that premature OA can develop with certain genetic disorders such as Stickler’s syndrome and familial chondrocalcinosis. Dr. Chitkara says ongoing research in this arena may lead to the development of “newer and more effective therapies.”

Q: Do you think there is potential for biologic therapies in treating OA?
A: Patrick Astourian, MS, PA-C, says cartilage regeneration represents a key target when it comes to the possibility of biologic therapies for OA in the future. He notes that new discoveries in stem cell technology may allow a process in which one can harvest a patient’s existing cartilage and grow it outside of the body. Astourian says we may also see chondrocytes induced to replicate and increase mitosis rates.

Early results of antiresorptive drugs have shown variable reduction in knee pain associated with OA, according to Dr. Dikranian. He adds that antiresorptive therapy has shown expected favorable effects on microscopic structural integrity and radiographic evidence of the decreased subchondral bone lesions associated with decreased biomechanical markers of cartilage degradation.

Key Insights On Current Therapies For OA Knee Pain

Dr. Chitkara says studies have found that the IL-1 cytokine plays a major role as researchers have shown an increased level of IL-1 among patients with knee OA. (Dr. Chitkara adds that the IL-6 cytokine may have a pathologic role as well.) There may eventually be a role for anti-IL-1 therapies in a subset of patients with OA, according to Dr. Chitkara. However, she says the current risk-to-benefit ratio does not allow for this intervention at this time.

The role of anti-TNF therapies in OA is less clear, according to Dr. Chitkara. Dr. Dikranian concurs. Dr. Dikranian notes that none of the currently available biologic therapies for inflammatory arthritis have shown convincing effects in OA. He points out that an open-label pilot study of adalimumab (Humira, Abbott) for the treatment of erosive and inflammatory hand OA did not reveal significant improvement of signs and symptoms with three months of treatment.

Drs. Chitkara and Dikranian agree that more research is necessary to determine if biologic agents have a future role in managing OA pain.

Q: How has ultrasound aided you in the diagnosis and treatment of OA?
A: Dr. Dikranian says the principal indications for using ultrasound include the delineation of changes within articular cartilage and identifying synovial and adjacent soft tissue pathology. Dr. Chitkara calls musculoskeletal ultrasound “a helpful tool in the bedside evaluation of a patient with joint pain.” She notes it also helps to differentiate inflammation of soft tissues around the joint from synovitis.

“The quality of results in ultrasonography is dependent on the characteristics of the equipment, knowledge of relevant anatomy and pathology, the experience of the sonographer, the techniques one uses and patient positioning,” points out Dr. Dikranian.
With further experience and standardization, Dr. Dikranian says ultrasound may emerge as an imaging tool for following the progression of OA.

One can also utilize ultrasound to facilitate the aspiration and injection of joints with OA, according to Dr. Dikranian. Astourian concurs, adding that ultrasound is also helpful in identifying areas where osteophytes are in contact with ligaments and tendons.
“Clinicians can then inject with more precision and better outcomes,” adds Astourian.

Ultrasound is “very good” at identifying small tears and collections of fluid that may also be causing pain, according to Astourian. For example, he points out that Baker’s cysts are common causes of posterior knee pain and one can use ultrasound to aspirate with more precision and less risk than a blind aspiration. Astourian says pes anserine bursitis is another common cause of knee pain that can be difficult to aspirate but is easy to identify with ultrasound.

In regard to ultrasound therapy, Dr. Chitkara says ultrasound waves generate heat to increase tissue extensibility. While ultrasound therapy requires multiple small sessions, Dr. Chitkara notes it “has the potential of increasing range of motion by increasing muscle contracture.” However, she concedes clinical studies have not shown great benefit and the optimal dosage, frequency and duration of sessions is still unclear. Dr. Chitkara says ultrasound therapy may be useful as an adjunct to physical therapy modalities and exercise.

Dr. Keller is Founder of San Diego Arthritis Medical Clinic in San Diego. He is the principal investigator of over 100 studies. Drs. Chitkara and Dikranian are practicing rheumatologists at the San Diego Arthritis Medical Clinic. Astourian is a physician assistant at the San Diego Arthritis Medical Clinic.