Athens University, 14, Makedonias Street, 153 41 Agia Paraskevi, Athens, Greece
Correspondence to: G. M. Papadimitriou. E-mail: gmpap{at}otenet.gr
SIR, The EULAR 2003 recommendations for knee osteoarthritis (OA) include a table with an evidence based final set of 10 recommendations [1]. Recommendation number 8 states: SYSADOA [symptomatic slow-acting drugs in osteoarthritis] (glucosamine sulphate, chondroitin sulphate, ASU [avocado and soya unsaponifiables], diacerein, and hyaluronic acid) have symptomatic effects and may modify structure. Concerning the modifying effect of glucosamine sulphate (GS), the authors refer to just one study (supported by a pharmaceutical manufacturer), including 106 patients with mild to moderate knee OA who showed delayed progression of joint space loss and improvement in pain and function scores with GS compared with placebo over a 3-yr period [2]. The authors also presented these EULAR recommendations at the annual British Society for Rheumatology meeting in Edinburgh in April 2004 and the abstract is included in the April 2004 supplement issue of Rheumatology [3].
I wonder if suggestions from studies (with questionable methodological considerations) offer a suitable evidence-based approach for the final EULAR recommendations. One basic comment is that the measure of the width of the medial tibiofemoral joint space in standing antero-posterior radiographs is a problematic approach and not a reliable index of structural modification [4]. It is also a common clinical observation that radiographic severity does not necessarily correlate with clinical symptoms.
We know that GS acts as a substrate for the biosynthesis of glycosaminoglycan chains (GAG) and subsequently for the production of proteoglycans (PG). Even if we accept that the absorption and metabolic fate of oral GS, until its distribution in the articular cartilage for the production of new PGs and cartilage repair, are all successful, we don't know if the quality of new products is normal. Besides, PG synthesis by chondrocytes is already increased in the early stages of the disease, but new PGs are different from normal ones in the composition and distribution of their GAG, the size of the PG subunit and their ability to aggregate with hyaluronic acid, and this can result in faulty organization of the repair molecules and could even accelerate the breakdown of the cartilage [5].
The same scepticism concerns all the SYSADOA in these final EULAR recommendations. Interestingly, concerning diacerein (DC) the authors identify only one randomized controlled trial in patients with knee OA [6]. Actually this study (again supported by a manufacturer) does not conclude structural modification but it compares only the efficacy of three DC dosages on symptoms of the disease.
I am afraid that at the moment there is no clear evidence for any of the available drugs or dietary supplements in the market that may modify OA progress. Even a symptomatic effect of GA is strongly disputed by many studies not supported by pharmaceutical manufacturers (e.g. [7]). These recommendations perhaps disorientate non-rheumatologists and young rheumatologists.
We know that OA is very slowly progressive and the diagnosis is usually based on morphological criteria. At that time OA is advancing, with PG concentration falling sharply, and the disease is progressing inexorably [5]. It is well known that ageing alone is not the cause of the disease, but age-related changes facilitate the development of the disease. It may be too late to modify age-related changes at the time of diagnosis.
I believe there is only one possibility for modifying the progression of the disease: very early diagnosis. MRI is a good diagnostic tool for the study of articular cartilage but it is expensive. Biochemical markers of bone and cartilage metabolism (BMBCM) help but they are not specific (they originate from several tissues, we don't know if their origin is catabolic or anabolic at a certain time, etc.) [8].When there is accurate and cost-effective imaging technology for articular cartilage and more specific (and cost-effective) BMBCM become available, the population at high risk for knee OA (e.g. age over 50, female sex, obese) could be screened for early diagnosis. There is now extensive research being done on BMBCM [9]. At the moment the only real management for this disease is to control pain and physical function of the joint using several factors or techniques (non-pharmacological, pharmacological, intra-articular or surgical). Non-pharmacological management, particularly exercises/physiotherapy/education, is the keystone of OA treatment, but unfortunately is under-utilized. In case of pharmacological treatment, as an adjunct [10], paracetamol is the first analgesic of choice as most guidelines suggest [11]. Doctors wishing to use GS or DC could include them in pharmacological management if they really control the pain and physical function of the joint, and probably for safety reasonsbut not as disease- or structure-modifying drugs. Medical doctors must be optimistic and convey their optimism to their patients, but in addition they have to be realistic and independent of the influence of pharmaceutical manufacturers.
The author has declared no conflicts of interest.
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