OSTEOARTHRITIS

What is osteoarthritis?

Osteoarthritis is the collective name for a family of bone diseases involving the degeneration of cartilage and abnormal growth of new bone and connective tissue. In late stage cases, abnormal bone growth causes visible bumps and ridges around the joints. Osteoarthritis can affect most joints, including the spine, but is more common in the knees, hips, feet and hands. Nodal osteoarthritis, affecting the finger joints, which occurs predominantly in middle-aged women, is clinically distinct from, for example, osteoarthritis of the knees, which is often related to obesity and shows a more even sex distribution. Symptoms depend on the joints affected, but include pain, stiffness and loss of function. Pain can become severe in the later stages of osteoarthritis, when replacement of the joint affected may be necessary. In 2005, there were 62,677 hip replacements and 62,818 knee replacements carried out in England and Wales.

Who does osteoarthritis affect and what does it cost?

By the age of 65, 80 per cent of people show evidence of osteoarthritis in X-rays, although only about 25 per cent have symptoms. Estimates have put the number of people suffering from osteoarthritis in the United Kingdom at 8.5 million, with more than 2 million visiting their GP each year because of osteoarthritis. The prevalence of osteoarthritis increases markedly with age in both men and women.

The total cost of arthritis (of which osteoarthritis makes up the largest component) to the NHS and social services has been estimated at £5.5 billion in 2000. Of this, the cost of operations to replace hip and knee joints was £405 million, other hospital costs were £259 million, GP consultations cost £307 million, and the cost of medications was £341 million. In addition, 206 million working days were lost in that year due to arthritis, corresponding to a loss of production of over £18 billion.

Present treatments and shortcomings

Current treatments for osteoarthritis are solely concerned with managing symptoms such as pain; there is no medication that has been proven to prevent the disease or modify its course. Exercises to build muscle are useful in people who are still active, simple painkillers or non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed for pain control, and corticosteroid injections into the joint can help in acute cases. In addition, various preparations are available for injection into the knee joint to improve the condition of the joints, but this does not alter the course of disease.

NSAIDs inhibit an enzyme called cyclo-oxygenase (COX), blocking the formation of inflammatory prostaglandins. COX exists in two forms: COX-1 and COX-2. Prostaglandins produced by COX-2 are inflammatory and damage the gut, leading to gastric ulcers and bleeding, but those from COX-1 have a protective effect. Of the older NSAIDs, some inhibit COX-2 more than COX-1 but are not entirely selective. Two of these are meloxicam (Mobic, Boehringer Ingelheim) and nabumetone (Relifex, Meda). Both have a lower risk of ulcers than NSAIDS that mainly inhibit COX-1, such as indomethacin, sulindac, aspirin and piroxicam.

COX-2 selective NSAIDs have been developed and introduced, but some have had to be withdrawn, following the finding of a raised incidence of heart problems. There is evidence that the risk of such side-effects differs from one selective COX-2 inhibitor to another and three remain available for pain relief in osteoarthritis. These are: celecoxib (Celebrex, Pfizer), etoricoxib (Arcoxia, Merck Sharp & Dohme), and lumiracoxib (Prexige, Novartis). Some of the older and widely used NSAIDs, ibuprofen and diclofenac, have also been associated with heart problems. While the risk of such side-effects remains small in all of these cases, the physician and patient must make any decision on the long-term use of high doses of painkillers on the basis of weighing up both risks and benefits.

What's in the development pipeline?

Additional pain-killers, including selective inhibitors of COX-2, are being studied for use in osteoarthritis and Daiichi-Sankyo has CS-706 in Phase 2 trial. NicOx is developing a version of naproxen (HCT 3012, naproxcinod), which has reached Phase 3 trial in osteoarthritis of the knee. This compound is expected not to show the blood pressure-raising effect of NSAIDs that may be responsible for the increased risk of heart problems. Pfizer also has a compound (CJ-23423) in phase 2 trial for osteoarthritis. Meanwhile, CombinatoRx Inc has reported positive results with a Phase 2 study of its CRx-102 for pain reduction in osteoarthritis of the hand.

New treatment approaches are also being studied by various companies. Sanofi-aventis has HOE 140 (icatibant) in Phase 2 trial and an oral form of calcitonin (SMC 021) being studied by Novartis and an anti-inflammatory compound (SC-84250) from Pfizer have reached the same stage. At Phase 1, Schwarz Pharma (UCB) is developing lacosamide and Wyeth (AGG-523, PLA-695) and Merck Sharp & Dohme (MK0822) also have compounds in development.

The possibility of modifying disease progress is also being investigated. Risedronate (Actonel, Procter & Gamble), a compound in the bisphosphonate group, slows bone destruction in osteoporosis and, as tiny fractures of bone at the joint surface have been suggested as a possible underlying cause of osteoarthritis, it might slow disease progress in osteoarthritis too. Although a reduction in pain was not found, risedronate did reduce the level of a marker of bone turnover that is associated with the progression of osteoarthritis. Also, GlaxoSmithKline is investigating an inhibitor (GSK 462795, relacatib) of an enzyme that may affect bone destruction, and this is at Phase 1.

FOR FURTHER INFORMATION CONTACT:

ARTHRITIS CARE
18 Stephenson Way
London, NW1 2HD
Phone: 0808 800 4050 (Helpline)
Website: www.arthritiscare.org.uk