Chondroitin Sulfate Effective for Knee Osteoarthritis

The efficacy of prescription-grade chondroitin sulfate is similar to that of celecoxib in reducing pain and improving function in patients with knee osteoarthritis (OA), according to results from a prospective, randomized, double-blind controlled trial.¹

Nonsteroidal anti-inflammatory drugs (NSAIDs), including celecoxib, are commonly used to treat patients with knee OA. Chondroitin sulfate — a major glycosaminoglycan component of the extracellular matrix of connective tissues, including bones — is categorized as a “symptomatic slow-acting drug for OA” (SYSADOA) and is commonly prescribed for the management of this condition.² Chondroitin sulfate is known to exert its beneficial anti-inflammatory action in human osteoarthritic chondrocytes through the inhibition of Nuclear Factor κ-B activation induced by Interleukin-1β.³

Approximately 37% of US adults ≥60 years of age have knee OA, and the number is expected to increase as rates of obesity and the aging population rise, according to data from a US Centers for Disease Control and Prevention National Health and Nutrition Examination Survey.⁴ Prescription chondroitin sulfate is not currently available in the United States; however, it is marketed as a dietary supplement, not approved by the US Food and Drug Administration.

The current study included outpatients from 5 European countries (n=603) who were older than 50 years and had primary knee OA of the medial and lateral femorotibial compartment. Patients were randomly assigned to receive one tablet of chondroitin sulfate 800 mg and one tablet of placebo celecoxib (n=199), one tablet of placebo chondroitin sulfate and one capsule of celecoxib 200 mg (n=199), or one tablet of placebo chondroitin sulfate and one capsule of placebo celecoxib (n=205), each combination administered daily for 6 months.

Patients were allowed to take paracetamol 500 mg to a maximum dosage of 3 g/d as rescue analgesia. No other pharmacologic or nonpharmacologic interventions for OA were allowed.

The 2 primary end points were the patient’s estimate of pain on a 100-mm visual analog scale (VAS) and the Lequesne Index, which assesses pain and function on a 0-to-24 scale.

Patients in the chondroitin sulfate and celecoxib treatment groups reported greater analgesia at the 6-month time point (but not at 1 or 3 months) than those in the placebo group (P =.001 and P =.009, respectively), as assessed by VAS scores; levels of pain reduction were similar in those 2 treatment groups (P =.446). Compared with placebo, chondroitin sulfate and celecoxib treatments also led to a greater reduction in Lequesne Index starting at 3 months (P =.05 and P =.027, respectively) and maintained after 6 months (P =.023 and P =.015, respectively).

“We confirmed the excellent safety profile of [chondroitin sulfate] that has been previously observed by others. This compelling benefit-risk profile, in light of the known clinical risks associated with chronic usage of NSAIDs and paracetamol, underscores the potential importance of pharmaceutical-grade [chondroitin sulfate] in the management of knee OA, especially in this older population requiring long-term treatment,” the researchers wrote. “More generally, this study corroborates the need for future clinical guidelines on the pharmacological management of knee OA to consider the study design, as well as the composition and quality of the test product, when assessing the effectiveness of SYSADOAs,” they added.

Donald M. Marcus, MD, an emeritus professor of medicine and immunology at Baylor College of Medicine in Houston, Texas, urged caution in a correspondence in the Annals of Rheumatic Diseases.⁵ Dr Marcus wrote that results from prior studies of chondroitin sulfate for pain relief in OA of the knee and hip have been conflicting. “In light of the apparent positive bias in industry-funded trials, I believe that acceptance of the positive results of this industry-funded study should be withheld pending confirmation by independently funded trials,” he wrote. 

Summary and Clinical Applicability

“These findings may change clinical practice in the countries where pharmaceutical grade chondroitin sulfate is available. These results cannot be extrapolated to [over-the-counter] or generic preparations,” said study lead author, Jean-Yves Reginster, MD, PhD, director of the Department of Public Health, Epidemiology and Health Economics and professor of Bioethics and Societal Medicine at the State University of Liege in Belgium. “Chondroitin sulfate can reasonably be considered as a background first-line therapy in osteoarthritis.”

• Pharmaceutical-grade chondroitin sulfate is as effective as celecoxib in alleviating pain and improving function in patients with knee OA.
• The findings are clinically relevant as they may provide clinicians with an alternative therapy to painkillers that can raise the risk of heart attack and stroke as well as gastrointestinal bleeding and ulcers. 

The study was funded by IBSA Institut Biochimique SA, a Switzerland-based pharmaceutical company manufacturing chondroitin sulfate. 

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Reference

1. Reginster J-Y, Dudler J, Blicharski T, Pavelka, K. Pharmaceutical-grade chondroitin sulfate is as effective as celecoxib and superior to placebo in symptomatic knee osteoarthritis: the ChONdroitin versus Celecoxib versus Placebo Trial (CONCEPT) [published online May 22, 2017]. Ann Rheum Dis. doi:10.1136/annrheumdis-2016-210860
2. Pecchi E, Priam S, Mladenovic Z, et al. A potential role of chondroitin sulfate on bone in osteoarthritis: inhibition of prostaglandin E₂ and matrix metalloproteinases synthesis in interleukin-1β-stimulated osteoblasts. Osteoarthr Cartil. 2012;20(2):127-135.
3. Largo R, Alvarez-Soria MA, Díez-Ortego I, et al. Glucosamine inhibits IL-1beta-induced NFkappaB activation in human osteoarthritic chondrocytes. Osteoarthr Cartil. 2003;11(4):290-298.
4. Dillon CF, Rasch EK, Gu Q, Hirsch R. Prevalence of knee osteoarthritis in the United States: arthritis data from the Third National Health and Nutrition Examination Survey 1991-94. J Rheumatol. 2006;33:2271-2279.
5. Marcus DM. Chondroitin sulfate for knee osteoarthritis [published online June 27, 2017]. Ann Rheum Dis. doi:10.1136/annrheumdis-2017-211915