Arthrosis is a degenerative disease of the articular cartilage that affects almost 50% of those over 65 years of age 1 . Of the total affected, approximately 20% will develop symptoms such as joint stiffness, pain and functional impotence. This disease is responsible for 30% of visits to the general practitioner in older adults and the second cause of disability in the elderly after cardiovascular disease. It also represents an important cause of work absenteeism.
TNVitamins Glucosamine/Chondroitin/MSM Complex Triple Strength (240 Tablets)
The key site of the damage is the articular cartilage, where a progressive degeneration associated with a chronic inflammation that causes stiffness and pain occurs. The cause of joint deterioration is not known but certain predisposing factors such as advanced age and obesity have been identified.
The classic treatment has been aimed at improving symptoms, generally using anti-inflammatory drugs such as NSAIDs and other important measures: weight control, exercise, kinesiotherapy and local treatments with capsaicin and infiltrations with corticosteroids. These measures are effective in controlling pain in the medium term but chronic therapy with NSAIDs can cause gastrointestinal and renal adverse effects that limit their use.
In recent years, drugs have appeared that act at the level of cartilage, interacting with components such as proteoglycans and interfering with the oxidative mechanisms dependent on free radicals, which are thought to be related to the state of inflammation and chronic degeneration. Among them is Glucosamine Sulfate, a compound derived from glucosamine which is a normal component of cartilage and joint fluid. This drug is postulated as a disease modifier, since it interferes with the aforementioned degenerative mechanisms and could alter the long-term prognosis in addition to alleviating the symptoms.
The evidence on this compound has been increasing, and there are currently three published systematic reviews and a three-year follow-up clinical trial that provide data in favor of the efficacy of 1500 mg daily of this drug. These four works are summarized in the following table.
- RCT = Controlled and randomized clinical trial ; NS = Not significant; IC = Confidence interval; RA = Absolute risk; RR = Relative risk; RRA = Absolute risk reduction; NNT = Number needed to treat
- 1 Evaluated by validated scales; 2 The results were reported in this paper as a difference in effectiveness between interventions.
- 0 = no difference 0.5 = mild efficacy 1 = moderate efficiency 1.5 = important efficacy
- 3 Effectiveness is reported as effect size
- 0 = effect equal to placebo 0.2 = mild effect 0.5 = moderate effect 0.8 = important effect
Both meta-analyzes found methodological difficulties in the studies that evaluated chondroitin, so it is difficult to interpret the results related to this drug (they are not included in the table)
4 It was used as a measure of joint structural change. The cutoff point for a significant reduction was 0.3 mm.
In the three meta-analyzes 2-3-4 , similar results were obtained regarding the efficacy of glucosamine; it was mild or at best moderately better than Aines or placebo to control pain, joint stiffness and improve overall function. It is convenient to consider, however, that rescue studies were allowed in most studies, so the efficacy to reduce pain and improve joint function is difficult to evaluate. It should also be noted that the studies that evaluated chondroitin (another compound frequently used and that comes from the articular cartilage) included few patients and in the majority significant methodological flaws were detected that prevent valid conclusions.
In 2001, a clinical trial was published in the Lancet 5 that evaluated 212 patients over 50 years of age with osteoarthritis of the knee randomized to receive glucosamine sulphate versus placebo, with three years of follow-up. This study is important because until then there was only data from a few weeks of follow-up. The primary end point was the average width of the joint space in the medial compartment of the knee, which they used as a measure of structural change in the joint. The limit of 0.3 mm was taken as a limit of significant reduction of the joint space. Another final point was the change in scales of pain, rigidity and functional limitation, items evaluated at the beginning of the study, the year and the three years.
At the end of the study, the average decrease in joint space of the glucosamine group was not significant, while those assigned to placebo showed an average decrease at three years of 0.31 mm (CI -0.48 to -0.13). .
Treating 1500 mg of glucosamine daily for three years resulted in an absolute risk reduction of joint space narrowing of 16% and it would be necessary to treat 6 patients for three years to prevent a significant decrease in joint space (NNT). 6).
The patients assigned to glucosamine had a mild to moderate improvement in the symptoms at three years and those who received placebo did not present changes in relation to the basal scales. There were no differences in the stiffness scales and the two groups consumed the same amount of rescue Aines. There were also no differences in relation to the adverse effects and these were mild and not clearly related to the treatment. The authors concluded that long-term glucosamine treatment can prevent structural changes related to osteoarthritis of the knee and significantly improve symptoms.
The most recent meta-analysis 4 was published in July of this year and included 15 studies that evaluated the efficacy in controlling symptoms and modifying the joint structure of both glucosamine and chondroitin. This review found that glucosamine treatment had a significant effect on the articular cartilage modifier compared to placebo, but not chondroitin. Also those treated with glucosamine improved the symptoms in relation to the placebo (see table).
According to the information provided by these four studies, glucosamine can be considered a valid and safe option for the symptomatic treatment of patients with osteoarthritis, and there would also be a modifying effect of the joint architecture, although there is still no clear the utility of this parameter in the evaluation of the effectiveness of the treatment. It is not possible to say the same about chondroitin; Studies with more patients are required, longer follow-up and better methodological quality to draw conclusions about this drug.
While these studies show that glucosamine improved symptom scores, the changes were at best moderate and it is not clear yet what the actual clinical translation of this difference is.
In addition, we must bear in mind that glucosamine treatment is more expensive than using some NSAIDs; the approximate monthly cost of a treatment with 1500 mg daily of glucosamine is $ 57, four times more expensive than paracetamol and almost twice as much as ibuprofen at adequate doses. Another point to consider is that glucosamine takes a little more than a month to start acting, so it is not recommended as rescue medication, and the actual amount of glucosamine that exists in commercial preparations is not completely clear. that it comes in the form of salt and there is a lot of variability between the different preparations.
For these reasons, the US NIH study that is already in the patient recruitment phase will be very welcome; this work will compare glucosamine sulphate with placebo and other long-term Aines and hopefully clarify these unresolved points.
As a practical conclusion, we have good quality evidence to indicate 1500 mg daily of glucosamine to a patient who has contraindicated Aines or in whom these drugs have not been effective, although the role of glucosamine as the first line of Treatment is not yet clear, especially due to the lack of long-term efficacy and safety studies and their high cost.