According to the Centers for Disease Control and Prevention (CDC), the bone-on-bone pain of osteoarthritis affects least 30 million Americans. Understandably, most people simply want the pain to go away, and turn to over-the-counter analgesics like ibuprofen or prescription drugs like celecoxib (also known as Celebrex) for relief.

The problem is, these options bring a world of side effects with them, including stomach and liver damage, risk of heart failure, and digestive discomforts, just to name a few. And none of the OTC or prescription options address the underlying physical causes of osteoarthritis—the wear and tear of the joints and destruction of cartilage, collagen, and the whole support structure that makes them work.

Glucosamine and chondroitin are two nutrients that have often been used in tandem to address the narrowing of joint spaces (causing bones to rub together) and the degradation of cartilage caused, in part, by continual inflammation.

Some of the leading research on chondroitin alone shows that it reduced the sensations of pain, not just in subjective survey scores, but in actual MRI brain scans of patients. Other work with the same material has shown that it decreased synovitis—fluid and swelling in the knee—by 50 percent compared with a 123 percent increase in the group taking acetaminophen. So while the idea of taking an over-the-counter or prescription drug initially seems to make sense, it doesn’t ultimately help in the long term.

And that’s what researchers have found regarding glucosamine and chondroitin. They are long-term joint restorers. In recent years, a lot of the press surrounding both of these ingredients has been a mixed bag, but the truth is, they take time to work effectively.

In a clinical study comparing a combination of glucosamine and chondroitin versus celecoxib, the combo and the drug ultimately had matching effects on knee osteoarthritis pain and symptoms after six months of use. The difference was that while each group saw 50 percent reductions in pain, swelling, and synovitis, the nutrients don’t cause risky side effects.

Abstracts:
Monfort J, Pujol J, Contreras-Rodríguez O, et al. Effects of chondroitin sulfate on brain response to painful stimulation in knee osteoarthritis patients. A randomized, double-blind, placebo-controlled functional magnetic resonance imaging study. Med Clin (Barc). 2017 Jun 21;148(12):539-547.

INTRODUCTION: Knee osteoarthritis is causing pain and functional disability. One of the inherent problems with efficacy assessment of pain medication was the lack of objective pain measurements, but functional magnetic resonance imaging (fMRI) has emerged as a useful means to objectify brain response to painful stimulation. We have investigated the effect of chondroitin sulfate (CS) on brain response to knee painful stimulation in patients with knee osteoarthritis using fMRI.

METHODS: Twenty-two patients received CS (800mg/day) and 27 patients placebo, and were assessed at baseline and after 4 months of treatment. Two fMRI tests were conducted in each session by applying painful pressure on the knee interline and on the patella surface. The outcome measurement was attenuation of the response evoked by knee painful stimulation in the brain.

RESULTS: fMRI of patella pain showed significantly greater activation reduction under CS compared with placebo in the region of the mesencephalic periaquecductal gray. The CS group, additionally showed pre/post-treatment activation reduction in the cortical representation of the leg. No effects of CS were detected using the interline pressure test.

CONCLUSIONS: fMRI was sensitive to objectify CS effects on brain response to painful pressure on patellofemoral cartilage, which is consistent with the known CS action on chondrocyte regeneration.

The current work yields further support to the utility of fMRI to objectify treatment effects on osteoarthritis pain.

Tío L, Orellana C, Pérez-García S, et al. Effect of chondroitin sulphate on synovitis of knee osteoarthritic patients. Med Clin (Barc). 2017 Jul 7;149(1):9-16.

OBJECTIVE: To evaluate by ultrasonography the effect of chondroitin sulfate (CS) on synovitis in patients with knee osteoarthritis (KOA). To collaborate in the understanding of the biochemical mechanisms involved in the synovial inflammation process.

METHODS: Randomized, single-blind, controlled trial involving 70 patients with primary KOA treated for 6 months with CS or acetaminophen (ACT). Evaluation of KOA status at baseline, 6 weeks, 3 and 6 months included: ultrasonography to assess synovitis (following the OMERACT expertise group definition), visual analogue scale and Lequesne index to measure pain and function, and ELISA to quantify inflammatory mediators in serum and synovial fluid.

RESULTS: Synovitis presence was reduced by 50% in the CS group while a 123% increase was observed in ACT group. Conversely, patients without initial synovitis and treated with ACT reached 85.71% synovitis onset, but only 25% in CS group. Both therapies improved articular function, but only CS resulted in significant pain improvement at the end of the treatment. Changes in RANTES and UCN synovial fluid concentration were associated with CS treatment.

CONCLUSIONS: Treatment with CS had a sustained beneficial effect, preventing synovitis onset or reducing its presence as well as reducing KOA symptoms. ACT ameliorated clinical symptoms but had no effect on inflammation. The CS anti-inflammatory effect could be related to the observed changes in RANTES and UCN concentration.

Hochberg MC, Martel-Pelletier J, Monfort J, et al. Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib. Ann Rheum Dis. 2016 Jan;75(1):37-44.

OBJECTIVES: To compare the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain.

METHODS: Double-blind Multicentre Osteoarthritis interVEntion trial with SYSADOA (MOVES) conducted in France, Germany, Poland and Spain evaluating treatment with CS+GH versus celecoxib in 606 patients with Kellgren and Lawrence grades 2-3 knee osteoarthritis and moderate-to-severe pain (Western Ontario and McMaster osteoarthritis index (WOMAC) score ≥301; 0-500 scale). Patients were randomised to receive 400 mg CS plus 500 mg GH three times a day or 200 mg celecoxib every day for 6 months. The primary outcome was the mean decrease in WOMAC pain from baseline to 6 months. Secondary outcomes included WOMAC function and stiffness, visual analogue scale for pain, presence of joint swelling/effusion, rescue medication consumption, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria and EuroQoL-5D.

RESULTS: The adjusted mean change (95% CI) in WOMAC pain was -185.7 (-200.3 to -171.1) (50.1% decrease) with CS+GH and -186.8 (-201.7 to -171.9) (50.2% decrease) with celecoxib, meeting the non-inferiority margin of -40: -1.11 (-22.0 to 19.8; p=0.92). All sensitivity analyses were consistent with that result. At 6 months, 79.7% of patients in the combination group and 79.2% in the celecoxib group fulfilled OMERACT-OARSI criteria. Both groups elicited a reduction >50% in the presence of joint swelling; a similar reduction was seen for effusion. No differences were observed for the other secondary outcomes. Adverse events were low and similarly distributed between groups.

CONCLUSIONS: CS+GH has comparable efficacy to celecoxib in reducing pain, stiffness, functional limitation and joint swelling/effusion after 6 months in patients with painful knee osteoarthritis, with a good safety profile.