The Critical Role Of The Meniscus In Osteoarthritis Of The Knee

Main Category: Arthritis News
Article Date: 02 Mar 2006 - 7:00am (UK)

Cartilage loss is a major component of osteoarthritis (OA), a joint disease that affects over 20 million Americans. In knee OA, cartilage loss is influenced by knee injury, as well as obesity and age. Every healthy knee is supported and protected by a pair of meniscus. This C-shaped tissue has many functions in the knee, including load bearing, shock absorption, and stability enhancement. 

The onset of knee OA after meniscectomy, the surgical removal of all or part of a torn meniscus, (the cartilage disk that acts as a cushion between the ends of bones that meet in a joint) is fairly common and traditionally considered a result of the joint injury that leads to the operation in the first place.

While meniscectomy appears to be a significant risk factor for OA, researchers know little about the effect of meniscal damage and abnormalities on cartilage loss in knees with a predisposition for the disease. The March 2006 issue of Arthritis & Rheumatism shares the results of a study that sheds new light on the importance of an intact and functioning meniscus for patients with symptomatic knee OA.

The study, led by David Hunter of Boston University School of Medicine, focused on 257 subjects enrolled in the Boston Osteoarthritis of the Knee Study. The majority, 58 percent, were men and the mean age was 66.6 years. All subjects met the American College of Rheumatology criteria for symptomatic knee OA, confirmed by X-rays and self-reports of frequent knee pain and stiffness. At the study’s onset and follow-up examinations at 15 and 30 months, participants underwent magnetic resonance imaging (MRI) of the more symptomatic knee. Using the MR images, researchers measured the position of the meniscus, as well as evaluated and scored the severity of meniscal damage. Among the MRI-assessed knees, 29% had a previous injury, 27% had a previous surgery, and 5% had a previous meniscectomy.

The researchers, as expected, found a high correlation between meniscal malposition and meniscal damage. The impact of meniscal abnormality on cartilage lost was most pronounced in the medial tibiofemoral joint–the inner joint connecting the knee to the lower leg. Each measure of meniscal misalignment was associated with an increased risk of cartilage loss. There was also a strong association of meniscal tears with cartilage loss. Reductions in the coverage and height of the meniscus, provoked by partial dislocation of the meniscus, also increased the risk of cartilage loss.

This study does not distinguish the type of meniscal tear that may propel cartilage loss or implicate meniscus damage as a cause of OA. It does call attention to the potential of a strong, whole meniscus to protect the knee from rapid devastation in the early stages of OA, and perhaps even mitigate the need for need replacement surgery. "At present, efforts are being made to preserve a damaged meniscus rather than remove it, and an industry of meniscal replacement is developing," Dr. Hunter notes. "Our study points to the need for critical, prospective evaluation of these new therapeutic options."
 

Inflammation causes tissue-specific depletion of vitamin B₆

En-Pei Chiang Donald E Smith,² Jacob Selhub,³ Gerard Dallal,⁴ Yi-Cheng Wang,¹ and Ronenn Roubenoff⁵

Arthritis Res Ther. 2005; 7(6): R1254–R1262. I

Abstract

Previously we observed strong and consistent associations between vitamin B₆ status and several indicators of inflammation in patients with rheumatoid arthritis. Clinical indicators, including the disability score, the length of morning stiffness, and the degree of pain, and biochemical markers, including the erythrocyte sedimentation rate and C-reactive protein levels, were found to be inversely correlated with circulating vitamin B₆ levels. Such strong associations imply that impaired vitamin B₆ status in these patients results from inflammation. In the present study we examined whether inflammation directly alters vitamin B₆ tissue contents and its excretion in vivo.

A cross-sectional case-controlled human clinical trial was performed in parallel with experiments in an animal model of inflammation. Plasma and erythrocyte and pyridoxal 5′-phosphate concentrations, urinary 4-pyridoxic acid excretion, and the activity coefficient of erythrocyte aspartate aminotransferase were compared between patients and healthy subjects. Adjuvant arthritis was induced in rats for investigating hepatic and muscle contents as well as the urinary excretion of vitamin B₆ during acute and chronic inflammation.

Patients with rheumatoid arthritis had low plasma pyridoxal 5′-phosphate compared with healthy control subjects, but normal erythrocyte pyridoxal 5′-phosphate and urinary 4-pyridoxic acid excretion. Adjuvant arthritis in rats did not affect 4-pyridoxic acid excretion or muscle storage of pyridoxal 5′-phosphate, but it resulted in significantly lower pyridoxal 5′-phosphate levels in circulation and in liver during inflammation. Inflammation induced a tissue-specific depletion of vitamin B₆. The low plasma pyridoxal 5′-phosphate levels seen in inflammation are unlikely to be due to insufficient intake or excessive vitamin B₆ excretion. Possible causes of decreased levels of vitamin B₆ are discussed.

Copper chelation with tetrathiomolybdate suppresses adjuvant-induced arthritis and inflammation-associated cachexia in rats

Arthritis Res Ther. 2005; 7(6): R1174–R1182.

Tetrathiomolybdate (TM), a drug developed for Wilson’s disease, produces an anti-angiogenic and anti-inflammatory effect by reducing systemic copper levels.

We have hypothesized that TM may be used for the therapy of rheumatoid arthritis and have examined the efficacy of TM on adjuvant-induced arthritis in the rat, which is a model of acute inflammatory arthritis and inflammatory cachexia. TM delayed the onset of and suppressed the severity of clinical arthritis on both paw volume and the arthritis score.

Histological examination demonstrated that TM significantly reduces the synovial hyperplasia and inflammatory cell invasion in joint tissues. Interestingly, TM can inhibit the expression of vascular endothelial growth factor in serum synovial tissues, especially in endothelial cells and macrophages. Moreover, the extent of pannus formation, which leads to bone destruction, is correlated with the content of vascular endothelial growth factor in the serum. There was no mortality in TM-treated rat abnormalities. TM also suppressed inflammatory cachexia.

We suggest that copper deficiency induced by TM is a potent approach both to inhibit the progression of rheumatoid arthritis with minimal adverse effects and to improve the well-being of rheumatoid arthritis patients.

 

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