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Long-term cold therapy to treat knee osteoarthritis: proof of concept


5 June, 2009  

While a cure for OA remains elusive, a new cryotherapy system mouldable to the affected body part offers the prospect of a safe alternative to traditional pharmacological management and may decrease cartilage breakdown

Yves Henrotin, Professor Bone and Cartilage Research Unit
Institute of Pathology CHU Sart-Tilman
Liège Belgium

Osteoarthritis (OA) is one of the most prevalent chronic diseases affecting the elderly. Its most prominent feature is the progressive destruction of articular cartilage, even if it is now accepted that OA is a global disease involving synovial  membrane, subchondral bone and periarticular soft tissues. The symptoms and signs characteristic of OA joints are pain, stiffness, limited joint function, gelling tenderness, bony enlargement and malalignment.

Cartilage degradation is driven by mechanical and biochemical factors. The main biochemical factors involved in this process are matrix metalloproteinases (MMPs) and reactive oxygen species (ROS), which are produced by chondrocytes, and synovial membrane cells. During OA pathology, synovial membrane undergoes a moderate inflammation, which may be most pronounced immediately adjacent to the OA lesion, indicating a link between cartilage lesion and synovium  inflammation.

The inflammatory reaction is triggered by mediators released from cartilage lesion, including inflammatory cytokines (mainly IL-1β and IL- 6), prostanoids (PGE2), matrix peptides (type II collagen peptide) and microcrystals. In response to these stimuli, synovial cells, including macrophages, T cells and fibroblasts, produce high levels of inflammatory cytokines (ie, IL-1β, TNFα), ROS, prostanoids (prostaglandins and leukotriens) and MMPs, which in turn directly degrade cartilage or stimulate chondrocytes to secrete more MMPs and ROS, resulting in an amplifying cycle and probably explaining the more rapid progression of chondropathy associated with flare episode.

Therefore, to trigger synovial membrane inflammation is a common therapeutic strategy, not only to relieve pain but also to reduce the inflammatory-associated cartilage degradation. Today, a cure for OA remains elusive, and the management of OA is largely palliative, focusing on the alleviation of symptoms (Table 1). Current recommendations for the management of OA include a combination of nonpharmacological and pharmacological modalities.[1]

Until now, the pharmacological management of OA has beeen dominated by nonsteroidal antiinflammatory drugs (NSAIDs) and analgesics (mainly paracetamol). Beside these conventional drugs, some new compounds classified as symptomatic slow-acting disease-modifying drugs (SYSADOAs) have shown symptomatic efficacy in human hip and knee OA. The term SYSADOA covers a range of agents, including glucosamine sulphate, chondroitin sulphate, diacerhein, hyaluronic acid (intra-articularly) and avocado soybean unsaponifiables (ASUs).

Nonpharmacological modalities of treatment are information and education, regular contact by phone, regular aerobic, muscle-strengthening and range of motion exercises, weight loss, walking aids, knee brace and thermal modalities, including heat and cold therapy. Currently, heat is applied for thigh muscle spasms and cold for inflamed joints. Several cryotherapy techniques are proposed, with cryogenic compresses currently the most frequently used. It is generally accepted that in cryotherapy the recommended interface temperatures have to be in the range of 5 to 15°C. Cryotherapy is deleterious below 5°C.

At temperatures of 35 to 36°C, as in synovitis and inflammatory joint disease, MMP activity, particularly aggrecanases, stromelysins and collagenases. can increase exponentially, leading to cartilage breakdown, whereas join temperatures of 30°C or lower result in negligible destruction.[2] Therefore, one goal of cold therapy should be  to decrease intra-articular temperature for a long-term period in actively inflamed joint. This can be achieved with isotherm systems with long-lasting and stable cooling effect.[3,4] Recently, we have tested a new isotherm mass, named  MORPHO (CE-marked device; previously FFleXX). MORPHO is a patented thermal structure – a set of cells containing the principal thermal material contained in an elastic articular system, which allows it to be moulded to fit any surface of the body, even in movement; and to induce a constant flow intended to cool the part to be treated with the right, preset constant temperature. A preliminary study conducted in small numbers of patients suffering from knee OA (n = 15) has  shown that MORPHO applied for one hour twice a day over seven days was more effective than a standard pharmacological treatment (NSAID and/or paracetamol) for relieving pain and improving joint mobility (personal communication).

In conclusion, the long-term cooling of OA joints with an external well-tolerated and safe cryotherapy system may potentially decrease cartilage breakdown by decreasing intra articular temperature. Continuous cryotherapy is also a safe alternative to pharmacological treatment in the management of OA symptoms.

TABLE 1. TREATMENT OF OA OF THE KNEE IS DIRECTED
TOWARDS:
• Reducing joint pain and stiffness
• Maintaining and improving joint mobility
• Reducing physical disability and handicap
• Improving health-related quality of life
• Limiting the progression of joint damage
• Educating patients about the nature of the disorder and its management.

References
1. Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidencebased, expert consensus guidelines. Osteoarthritis Cartilage 2008;16:137-62.
2. Horvath SM, Hollander JL. Intraarticular temperature as a measure of joint reaction. J Clin Invest 1949;28:469-73.
3. Oosterveld FG, and Rasker JJ. Effects of local heat and cold treatment on surface and articular temperature of arthritic knees. Arthritis Rheum 1994;37:1578-82.
4. Oosterveld FG, Rasker JJ, Jacobs JW, Overmars HJ. The effect of local heat and cold therapy on the intraarticular
and skin surface temperature of the knee. Arthritis Rheum 1992;35:146-51.