Osteoarthritis: new diagnostic test may help detect it earlier
Fluorescent probe could help detect and track osteoarthritis in its early stages
Osteoarthritis is one of the 10 most disabling diseases in developed countries today, affecting nearly one in 10 men and one in five women aged over 60. In most cases, the joint disease is diagnosed only in an advanced stage, when a patient is in pain.
Earlier diagnosis might lead to better management and patient outcomes. A new fluorescent probe, devised by researchers from the Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts, could make the detection and monitoring of early stage osteoarthritis easier.
The fluorescent probe, reported in a study published in the February issue of Arthritis & Rheumatology, makes it easy to see the activities that lead to cartilage breakdown in the initial and moderate stages of osteoarthritis, which is needed for early detection and adequate monitoring of the disease.
"The imaging tests most frequently used, X-rays, don't indicate the level of pain or allow us to directly see the amount of cartilage loss, which is a challenge for physicians and patients," says Averi A. Leahy, co-lead author of the study.
An optical imaging system detects and measures the near infrared wavelengths emitted by the probe, giving doctors a non-invasive look inside the knee.
Osteoarthritis is the most common type of arthritis, which causes pain, swelling, and reduced motion by breaking down the cartilage that normally covers the ends of our bones to absorb the shock of movement. It normally results from an injury, or long-term wear and tear of the hip, hands, or knees.
According to the World Health Organisation, 9.6 per cent of men and 18 per cent of women aged over 60 years have symptomatic osteoarthritis.
A local survey by Chinese University in 2000 revealed that 17 per cent of men and 24 per cent of women over the age of 50 had persistent knee pain, and 7 per cent of men and 13 per cent of women suffered from osteoarthritis.
There are no current statistics available on the number of osteoarthritis cases in Hong Kong, but the age-related disease is expected to have an increasing impact on the territory's health care system due to the ageing population.
More than 20 per cent of the local population is expected to be 65 or older by the early 2020s. But it's not just the elderly who are affected by osteoarthritis - the Centre for Health Education and Health Promotion at Chinese University is getting more inquiries from younger people, some in their late 30s, seeking help for joint pain.
The Tufts researchers conducted lab tests on 54 mice over a two-month period. The right knees of the mice were affected by injury-induced osteoarthritis and served as the experimental group (the mice received pain medication). The healthy, left knees of the mice served as the control group.
The researchers injected a liquid molecule, invisible to the human eye, into the knee joints of mice to detect the activity leading to cartilage loss, a key characteristic of osteoarthritis. Fortnightly images of each knee were taken to determine if the fluorescent probe emitted a signal.
Strikingly, the signal became brighter in the injured right knee, at every examined time point, through the early to moderate stages of osteoarthritis. The probe emitted a lower signal in the healthy left knee, and did not increase significantly over time.
While the findings were promising, Leahy says it's still only early-stage work done with mice. "We cannot predict if or when this form of monitoring could be done on humans," she says. "Previous research had identified that an increase in enzymes called matrix metalloproteinases (MMP) contributes to the cartilage degradation that occurs with osteoarthritis. The fluorescent probe was introduced into the knee joint and measured MMP activity.
"This probe has not been tested or approved for use in humans. We used a probe that has a base that is similar to one that has been approved by the FDA, but ours is enzyme-specific."
The next step of the research is to monitor the fluorescent probe over a longer period of time to determine whether the same results are seen during the late stages of osteoarthritis.
Li Zeng, associate professor in the department of integrative physiology and pathobiology at Tufts School of Medicine, hopes to use the probe to help develop treatments for other animals such as dogs, as they are also prone to osteoarthritis.
There are two main categories of treatment available to those with osteoarthritis - conservative and operative. Conservative treatments include weight reduction, modification of daily activities (for example, avoiding carrying heavy goods, or climbing stairs), appropriate exercise, use of walking aids, analgesics, physical therapy and viscosupplement (oral or intra-articular injection).
For young patients with osteoarthritis limited to just one part of the knee joint, operative treatment could include either high tibial osteotomy (that is, bone cut to shift the load to the other side of knee joint) or a unicompartmental knee replacement. For older patients or young patients with osteoarthritis involved diffusely, total knee replacement might be the only option.
The probe could help with early detection and avoidance of surgery. But Dr Yuen Wai-hong, a specialist in orthopaedics and traumatology in Hong Kong, is sceptical that the probe will have any practical use in humans.
"The florescent probe may be useful for research. However, in my opinion, it is not useful for clinical management of patients at present," says Yuen, who is not related to the study.
"Osteoarthritis is a slowly progressive disease, and can be diagnosed by a patient's history and physical examination. It is well known that the severity of a patient's symptom has poor correlation with the severity of radiographic osteoarthritis changes, so I am not sure if the activity of the probe signal has any correlation with the patient's symptoms.
"The management of patients relies on the severity of patients' symptoms, not on the X-ray or findings of any investigation."