knee OA: tumeric helps

 A small study confirmed symptomatic improvement for knee osteoarthritis with the spice tumeric (see knee arthritis tumeric helps AIM2020 in dropbox, or doi:10.7326/M20-0990)

Details:

-- 70 people with symptomatic knee osteoarthritis, older than 40yo, knee pain of at least 40 mm on the Visual analog scale (VAS) of 0-100, and symptomatic osteoarthritis along with a moderate amount of ultrasonographically-defined effusion-synovitis 

    --Mean age 61, 56% female, BMI 30,

-- mean VAS score 55, mean effusion-synovitis 24 mL, mean cartilage T2 relaxation time 44 ms, radiographic joint space narrowing in 71%,  

-- mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score 1000 (score from 0-2400)

    --WOMAC pain score 200 (0-500), function score 720 (0-1700), stiffness score 92 (0-200)

-- baseline pain medications: acetaminophen 22%, NSAIDs 10%, opioids 3%

-- supplements: glucosamine with or without chondroitin 18%, vitamins 38%, fish oil 20%, coenzyme Q 3%

-- randomized to 2 capsules of 500 mg/d Curcuma longa (CL, the scientific name for tumeric), vs matched placebo: This is equivalent to 5 teaspoons of tumeric (though, the literature suggests that there is wide variability of what the teaspoon equivalents really are). Of note, the average adult in India consumes 2-2.5 grams per day (ie, 2000-2500 mg/d)

-- Primary outcomes: change in knee pain on VAS; effusion-synovitis volume on MRI. The minimal clinically important difference (MCID) for the VAS was considered to be 18 mm on the 100 mm scale

-- secondary outcomes: change in WOMAC pain scale and cartilage composition values

-- Study lasted 12 weeks

Results:

--tumeric vs. placebo:

    -- pain scale (VAS): -23.8 (decreased) with tumeric vs -14.6 for placebo, difference of -9.1 mm (-17.8 to -0.4), p=0.039 [though not reaching the MCID value of 18]

    -- no significant change in MRI effusion-synovitis volume of 3.2 mL (-0.3 to 6.8)

--WOMAC knee pain index: -47.2 mm (-81.2 to -13.2), p=0.006 (range 0-500)

--WOMAC knee function: -112.3 (-222.8 to -1.7), p=0.047 (range 0-1700)

--WOMAC knee stiffness: -20.2 (-36.9 to -3.4), p=0.019 (range 0-200)

--weight-bearing pain: -25.9 (-47.4 to -4.5), p=0.018 (range 0-300)

--non-weight bearing pain: -21.3 (-36.3 to -6.4), p=0.005 (range 0-200)

--9 patients in placebo group began or increased pain meds vs 4 in the CL group; 4 in CL group stopped or decreased pain meds vs 0 in placebo group

--post-hoc analysis: relative to median baseline effusion-synovitis volume of 20.45ml, people having smaller volume and getting CL had significant changes clinically (VAS -18.5; WOMAC pain -96.4, function -252.5, stiffness -37.9), but no significant changes in those with higher than median value at baseline [for the smaller volume group, did reach MCID]

-- adverse effects: similar, 14 (39%) on medication vs 18 on placebo (53%). 2 events on medication and 5 in the placebo group were considered to have been possibly treatment related

Commentary:

--so, taking CL at this quantity (or, presumably, eating sufficient tumeric) is associated with a consistent array of clinical improvements in knee OA, especially in those with smaller degrees of effusion-synovitis volume, though there was no significant change in MRI findings

    --in fact, though a post-hoc analysis, those with smaller effusion-synovitis volumes (in this case <20.45ml), had VAS more than the 18 difference in the VAS that the researchers considered to be the minimum for being clinically significant (MCID)

    --there was also a significant difference in MRI findings of effusion-synovitis volume depending on the initial volume, with small volume favoring CL and large volume placebo

    --and, by way of comparison, in a differentstudy acetaminophen had a VAS difference of only 3.7mm on the 100-point VAS and a less favorable safety profile

    --and another study found that effect size for CL was somewhat higher than for acetaminophen, COX-2 inhibitors and NSAIDs vs placebos
-- also, the use of fewer pain relievers found above in the CL group might decrease the actual measured effect size in this study

-- osteoarthritis is the common endpoint of different disease pathways, some OA associated with more inflammation (also reflected in higher high-sensitivity C-reactive protein levels) and associated with several pro-inflammatory cytokines including IL-1 beta, TNF alpha, and IL-6 (which all contribute to the progression of cartilage loss)

    -- localized inflammation in those symptomatic and with radiographic findings of osteoarthritis is found in about 50% of patients.

        -- the above study also found limited utility for knee xrays is determining the presence of knee OA,; this was also found in the Framingham prospective study where both the sensitivity and specificity was poor

-- effusion-synovitis volume on MRI or ultrasound is associated with cartilage defects, loss of cartilage volume, and increased bone marrow lesions (also not seen on xray...), as well as clinical progression of OA including future need for knee replacement

-- CL has been used for arthritis for eons, being part of both Ayuvedic and traditional Chinese medicine

-- CL has been found to have anti-inflammatory, analgesic, antioxidant, anticancer, and wound-healing properties

-- a systematic review found that CL reduced knee pain and improve quality of life, though the studies were done in China, were not methodologically rigorous and opened to bias, as well as of questionable generalizability to Western populations

-it was surprising that those with smaller effusion-synovitis volume did better. unclear why. ??those with higher volume had more advanced disease and were less amenable to therapy.  or, a short 12-week study was insufficient to find differences??  the fact that the treatment effect clinically did not plateau by 12 weeks suggest that additional treatment with CL might have been more effective, and possibly also in those with more advanced disease/more inflammation/larger effusion-synovitis volumes

Limitations of study:

--the biggest limitation is probably the short duration of the study. was the effect going to continue to increase and for how long?, decrease?

--also, this was a pretty small study. might be useful to have larger study. and perhaps with tumeric added to food instead of a pill???

--do the MRI changes take more time than the 12-week trial to become evident? would b useful to have longer followup

--over 50% of the patients were on supplements, which may be a select group and limit the generalizability and openness to the study (though this was an RCT, and non-generalizable patient population)

so, pretty interesting. pretty safe and seemingly effective therapy. would be great to have a larger study with a specific quantity of tumeric added to foods. only downside that i know of is that tumeric does tend to stain plates, pans and maybe teeth a bit. in fact, in this study there were more adverse effects with placebo....

also, this study confirms the limited utility of knee xrays in diagnosing knee OA, where radiographic joint space narrowing was found in only 71% though there were more sensitive radiologic markers (MRI) and clinical symptoms

geoff

 

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