Abstract
Background
Curcumin, a substance in Turmeric spices, has been shown to exhibit anti-inflammatory and chondroprotective properties in several preclinical studies. However, there is limited research on the efficacy and side effects of oral curcumin in treating hand osteoarthritis. Thus, the primary aim of this pilot study was to assess the therapeutic effects and potential adverse effects of curcumin in patients with hand osteoarthritis, specifically in terms of pain reduction, improvement in functional outcomes, and relevant blood test parameters.
Method
This pilot prospective double-blind, randomized controlled trial included patients over 50 years old diagnosed with hand osteoarthritis. Participants received a three-month oral administration of either a turmeric capsule containing curcumin (170 mg/day) or a placebo. The outcomes measures included the Visual Analogue Scale (VAS) for pain, the Disabilities of Arm, Shoulder, and Hand (DASH) score, hand grip and pinch strength, as well as side effects and blood tests at one, two, three, and six months.
Results
Twenty-seven patients were enrolled in this study—13 in the curcumin group and 14 in the placebo group. Baseline characteristics were similar between both groups. Although patients in the curcumin group showed reductions in VAS pain scores and improvements in DASH scores after one month, the differences were not statistically significant. However, by the third month, patients in the curcumin group demonstrated significant reductions in VAS pain scores at rest and during activity compared to the baseline scores, with mean differences of 1.37 ± 0.64 (p-value = 0.032) and 1.74 ± 0.73 (p-value = 0.017), respectively. Additionally, their DASH scores improved significantly with a mean difference of 11.84 ± 5.88 (p = 0.044). One patient in the curcumin group experienced gastrointestinal (GI) side effects, leading to withdrawal from the study, but no other adverse effects were reported.
Conclusion
Based on the results of this pilot study, the authors conclude that a three-month regimen of low-dose oral curcumin may improve pain and functional scores in patients with hand osteoarthritis compared to placebo. However, GI discomfort remains a potential side effect to monitor. Overall, curcumin appears to be a safe and feasible alternative treatment option for hand osteoarthritis, and a larger, definitive randomised controlled trial is warranted.
Trial registration
The trial has been registered in the Thai Clinical Trials Registry(TCTR) database. The identification number is TCTR20210929003.
Keywords: Curcumin, Hand osteoarthritis, Osteoarthritis of hand, Tumeric, Curcuma longa
Background
Hand osteoarthritis is a prevalent condition among the elderly, affecting approximately 12% of individuals over the age of 50, with a higher prevalence in women than men [1]. The disease typically presents with pain following prolonged use of the fingers and stiffness in the finger joints, which usually lasts less than 30 min. These symptoms can significantly disrupt daily activities [2]. The current treatment for hand osteoarthritis primarily begins with conservative approaches such as activity modification, physical therapy, and pain management. Medications include the use of non-steroidal anti-inflammatory drugs (NSAIDs), intra-articular corticosteroid injections, paracetamol (acetaminophen), and weak opioids [3]. Among these, NSAIDs are the most commonly recommended. However, long-term use of NSAIDs can lead to serious side effects, particularly in elderly patients. These adverse effects include cardiovascular complications (e.g., heart failure), acute kidney injury, and gastrointestinal bleeding [4].
Curcumin, a bioactive compound extracted from turmeric (Curcuma longa), is a traditional herb commonly used in its yellow pigmented powder form in Indian, Chinese and Thai cuisines, primarily to enhance the flavour of spicy dishes. In vitro study of human articular chondrocytes and in osteoarthritic rat models, the potential positive effects of curcumin for treating osteoarthritis were shown by the following mechanisms, (1) Anti-inflammation, by regulation of gene expression for pro-inflammatory activator(nuclear factor kappa-B signalling pathway) [5–7] (2) Anti-catabolic process, by inhibition of matrix metalloproteinase, thereby reducing the degradation of type II collagen, a major component of cartilage [7–10] (3) Improving the articular chondrocyte anabolism, cartilage extracellular matrix homeostasis especially collagen production [11, 12] (4) Prevention of the chondrocyte apoptosis by reducing the oxidative stress [13] (5) Controlling the quality of mitochondria in chondrocyte, by promoting mitophagy process [14, 15].
In previous human studies, curcumin has also demonstrated effectiveness in reducing pain in patients with knee osteoarthritis [16–18]. In addition, curcumin is safe, even at high daily doses over prolonged periods [19–21]. However, its impact on hand osteoarthritis remains unclear. As the evidences previously mentioned, it is hypothesised that curcumin could serve as a symptomatic slow-acting drug for hand osteoarthritis. Therefore, the objective of this study was to evaluate whether curcumin could reduce pain, alleviate hand stiffness, and improve hand function in patients with hand osteoarthritis. Pain was assessed using the Visual Analog Scale (VAS), while hand function was measured using the DASH questionnaire, as well as grip and pinch strength tests. In addition, side effects and relevant blood test results associated with curcumin usage were recorded.
Materials and methods
Following approval from the Institutional Review Board of Ramathibodi Hospital, Mahidol University (COA.MURA2021/763), this double-blinded randomised control trial study was conducted within the Orthopedic department at Ramathibodi Hospital from July 2022 to December 2023. The inclusion criteria encompassed patients aged over 50 years, diagnosed with hand osteoarthritis according to the American College of Rheumatology criteria for the condition [22]. Participants were required to present with hand pain or stiffness, as measured by a visual analogue scale (VAS) score of no less than three points. Exclusion criteria included patients with a history of major hand trauma, such as fractures or dislocations, previous hand surgery, inflammatory joint diseases (e.g., rheumatoid or psoriatic arthritis), and those with severe medical comorbidities, including the use of antiplatelet or anticoagulant drugs, abnormal liver function, chronic kidney disease, or allergies to curcumin or NSAIDs.
Baseline assessments for all patients included VAS scores for hand pain at rest, during activity, and morning stiffness (0–10 scale). Additionally, participants completed the DASH questionnaire (Thai version) to evaluate their quality of life and hand function [23]. Hand grip and pinch grip were measured using a hand-held dynamometer. Laboratory tests included a complete blood count (CBC), creatinine, electrolytes, liver function tests, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) to monitor safety and assess inflammatory response. Hand radiographs in anteroposterior and oblique views were taken to exclude other inflammatory joint diseases, by assessing for radiographic features such as erosions and periarticular osteopenia [24]. All participants provided informed consent, and demographic data, including age, gender, height, weight, body mass index (BMI), and dominant hand, were collected.
As this was a feasibility study, no conventional sample size calculation was performed, and the study was not powered to test the relative efficacy of curcumin versus placebo. Initially, it was estimated that 74 participants would be required to observe variability in the outcomes, with the intention of powering a full-scale trial. However, a proportionally reduced sample size was deemed sufficient to test the primary feasibility outcomes. The clinical trials unit and the trial steering committee agreed on this adjustment based on prior pilot study sample sizes [25–30]. Ultimately, 27 participants were recruited for this study.
The randomization of treatment allocation (curcumin group vs. placebo group) was carried out using STATA 16.1 software (Stata Corp in College Station, Texas, USA) with a block randomisation method. The treatments were sealed in envelopes and organised according to the participants’ enrolment order to maintain blinding of the physicians to treatment allocation. Outcome assessors remained blinded to the treatment data throughout the follow-up period.
In the curcumin group, participants received a drug containing 500 mg of turmeric powder (Curcuma longa L.) from Chaophraya Abhaibhubejhr Hospital, equivalent to 28.75 mg of curcuminoids per capsule. The medication, indistinguishable in appearance from the placebo, was administered as two capsules, three times daily for three months. Rescue medications (acetaminophen and naproxen) were provided for additional pain management if needed. Participants were also asked to maintain a Visual Analog Scale (VAS) pain diary, recording daily pain levels (scale 0–10) in three categories: pain at rest, pain during activity, and morning hand stiffness. Follow-up visits were scheduled at 1, 2, 3, and 6 months after treatment initiation.
At each follow-up visit, the VAS pain diary was collected, and the mean VAS scores for the preceding month were calculated for the three categories (at rest, during activity, and morning stiffness). Additionally, the participants completed the DASH questionnaire to assess hand function. Hand grip and pinch strength (in kilograms) were measured using a handheld dynamometer, and blood tests were repeated as previously outlined. Potential side effects related to the treatment were also monitored. After three months of medication use, patients discontinued the treatment and were monitored for an additional three months, for a total follow-up period of six months. This phase was intended to compare pain, hand function, and laboratory test results between the treatment period and the drug discontinuation phase.
The primary study endpoint was to evaluate the therapeutic effects of curcumin compared with placebo on pain reduction and functional improvement (hand grip, pinch strength, and DASH score) at one month. Secondary endpoints included the evaluation of pain reduction and functional improvement at 2, 3, and 6 months. The study also monitored adverse effects of curcumin throughout the trial period.
Statistical analysis
The analysis and presentation of results adhered to the guidelines of the CONSORT 2010 statement: extension to randomised pilot and feasibility trial [26]. Data analysis was performed using SPSS Inc., Version 18.0 (PASW Statistics, Released 2009) Continuous variables were expressed as means and medians, while categorical variables were presented as percentages. For the comparison of demographic data between the curcumin and placebo groups, the independent t-test was used for normally distributed continuous variables, while the Mann–Whitney U test was applied to non-normally distributed data. To account for the interaction between treatment group and time, a mixed-model analysis with mean (S.E.) was employed to assess the statistical significance of the primary and secondary endpoints. A p-value of less than 0.05 was considered statistically significant.
Results
A total of 27 patients were included in this study, with 13 assigned to the curcumin group and 14 to the placebo group. The CONSORT flow chart outlining patient allocation is presented in Fig. 1. The average age of participants was 63.54 ± 5.52 years in the curcumin group and 65.07 ± 5.21 years in the placebo group. The mean body mass index (BMI) was 24.02 ± 3.42 in the curcumin group and 24.86 ± 2.75 in the placebo group. Notably, 24 patients (88%) were female. The patient characteristics, including VAS pain scores, hand grip strength, pinch strength, DASH scores, and laboratory results, are detailed in Table 1, with no statistically significant differences observed between the groups.
Fig. 1.
CONSORT flow chart
Table 1.
The patient characteristics
| Curcumin group (N = 13) |
Placebo group (N = 14) |
p-Value | |
|---|---|---|---|
| Age, Mean (S.D.) | 63.54 (5.52) | 65.07 (5.21) | 0.465 |
| BMI, Mean (S.D.) | 24.02 (3.42) | 24.86 (2.75) | 0.486 |
| Gender (Female/Male) | 13/0 | 11/3 | 0.222 |
| VAS Pain at rest, Median (IQR) | 3 (3,5) | 3 (2,4) | 1.000 |
| VAS Pain at activity, Median (IQR) | 4 (3,5) | 3 (3,5) | 0.408 |
| VAS morning stiffness, Median (IQR) | 3 (3,6) | 3 (3,5) | 1.000 |
| Hand grip, Rt side (kg), Mean (S.D.) | 22.35 (3.29) | 24.82 (5.03) | 0.152 |
| Hand grip, Lt side (kg), Mean (S.D.) | 19.35 (3.52) | 21.71 (5.67) | 0.208 |
| Tip pinch, Rt thumb (kg), Mean (S.D.) | 3.88 (0.92) | 4.68 (1.15) | 0.061 |
| Tip pinch, Lt thumb (kg), Mean (S.D.) | 3.75 (1.07) | 4.25 (1.35) | 0.299 |
| DASH, Median (IQR) | 33.62 (14.17, 45.83) | 31.665 (5, 40) | 0.709 |
| WBC, Mean (S.D.) | 6,602.31 (1,818.39) | 6,581.54 (1,465.156) | 0.975 |
| ESR, Median (IQR) | 33 (25, 35) | 19 (12, 38) | 0.073 |
| CRP, Median (IQR) | 1.52 (1, 4.5) | 1.14 (1, 2.88) | 0.721 |
| Creatinine, Mean (S.D.) | 0.72 (0.09) | 0.76 (0.21) | 0.560 |
| GFR, Mean (S.D.) | 88.64 (11.27) | 86.63 (15.40) | 0.708 |
| AST, Mean (S.D.) | 25.46 (5.43) | 23.54 (5.90) | 0.395 |
| ALT, Mean (S.D.) | 20.77 (7.36) | 22.54 (7.59) | 0.552 |
| ALP, Mean (S.D.) | 75.54 (17.24) | 77.31 (14.90) | 0.782 |
| GGT, Median (IQR) | 21 (16, 30) | 24 (16, 31) | 0.537 |
| TB, Median (IQR) | 0.5 (0.4, 0.8) | 0.6 (0.5, 0.8) | 0.510 |
| DB, Mean (S.D.) | 0.23 (0.11) | 0.24 (0.09) | 0.846 |
BMI Body mass index, VAS Visual analogue scale, DASH Disabilities of the arm, shoulder, and hand, WBC White blood cell, ESR Erythrocyte sedimentation rate, CRP C-reactive protein, GFR Glomerular filtration rate, AST Aspartate transaminase, ALT Alanine transaminase, ALP Alkaline phosphatase, GGT Gamma-glutamyl transferase, TB Total bilirubin, DB Direct bilirubin
Graphs in Fig. 2. illustrate the changes over time in the mean (standard error) values of VAS hand pain at rest, VAS hand pain during activity, VAS hand morning stiffness, DASH score, hand grip, pinch strength at baseline, 1 month, 3 months, and 6 months for both groups. The data showing these changes over time, along with the data on rescue drug usage, are summarised in Table 2.
Fig. 2.
Changes over time in mean VAS scores (for pain at rest, pain during activity, and morning stiffness), DASH scores, hand grip strength, and pinch strength at baseline, 1 month, 3 months, and 6 months
Table 2.
Study parameters, mean (S.E.) changes over time
| Mean score | Baseline | At 1 month | At 3 months | At 6 months | ||||
|---|---|---|---|---|---|---|---|---|
| Placebo | Curcumin | Placebo | Curcumin | Placebo | Curcumin | Placebo | Curcumin | |
| Pain at rest | 3.44 ± 0.57 | 4.48 ± 0.57 | 3.63 ± 0.57 | 3.94 ± 0.58 | 2.62 ± 0.60 | 2.30 ± 0.61 | 2.45 ± 0.62 | 3.26 ± 0.63 |
| Pain at activity | 4.18 ± 0.59 | 4.92 ± 0.60 | 3.97 ± 0.59 | 4.12 ± 0.60 | 3.51 ± 0.63 | 2.50 ± 0.64 | 2.96 ± 0.66 | 3.98 ± 0.67 |
| Morning stiffness | 4.12 ± 0.65 | 4.47 ± 0.66 | 3.74 ± 0.65 | 3.56 ± 0.66 | 2.99 ± 0.68 | 2.03 ± 0.70 | 2.30 ± 0.71 | 2.99 ± 0.72 |
| DASH | 31.07 ± 4.61 | 36.38 ± 4.63 | 32.17 ± 4.59 | 27.28 ± 4.80 | 24.12 ± 4.90 | 17.58 ± 5.06 | 25.67 ± 5.17 | 24.71 ± 5.24 |
| Right hand grip | 25.16 ± 1.20 | 22.90 ± 1.31 | 25.88 ± 1.20 | 23.23 ± 1.31 | 25.32 ± 1.23 | 24.05 ± 1.32 | 23.81 ± 1.25 | 22.94 ± 1.34 |
| Left hand grip | 21.38 ± 1.31 | 19.74 ± 1.42 | 22.59 ± 1.30 | 20.34 ± 1.42 | 22.75 ± 1.33 | 21.46 ± 1.44 | 21.41 ± 1.35 | 19.92 ± 1.45 |
| Right pinch strength | 4.82 ± 0.29 | 4.02 ± 0.32 | 4.99 ± 0.29 | 4.85 ± 0.32 | 5.20 ± 0.31 | 4.63 ± 0.33 | 4.88 ± 0.32 | 4.61 ± 0.34 |
| Left pinch strength | 4.19 ± 0.30 | 3.76 ± 0.33 | 4.78 ± 0.30 | 4.04 ± 0.32 | 4.98 ± 0.32 | 4.87 ± 0.34 | 4.76 ± 0.33 | 4.49 ± 0.35 |
|
Acetaminophen usage (tablet per month) |
- | - | 1.64 ± 1.42 | 1.92 ± 1.06 | 1.00 ± 0.68 | 1.00 ± 0.91 | 3.00 ± 1.56 | 3.07 ± 2.08 |
|
Naproxen usage (tablet per month) |
- | - | 1.78 ± 0.96 | 1.84 ± 1.42 | 1.71 ± 0.98 | 1.84 ± 1.53 | 2.28 ± 1.45 | 2.30 ± 1.66 |
DASH Disabilities of the arm, shoulder, and hand
Study parameter
In the between-group analysis (Fig. 2), no significant differences were observed in VAS hand pain at rest, VAS hand pain during activity, VAS hand morning stiffness, DASH score, hand grip, pinch strength and rescue drug usage at 1, 3, and 6 months.
However, in the within-group comparison at 3 months, the curcumin group demonstrated significant improvements compared to baseline. There was a reduction in VAS hand pain at rest by 1.37 ± 0.64 (p = 0.032) and in VAS hand pain during activity by 1.74 ± 0.73 (p = 0.017) compared to the placebo group. Additionally, the curcumin group exhibited a significant improvement in DASH scores at 3 months, with a reduction of 11.84 ± 5.88 (p = 0.044) from baseline. Further details of the within-group comparison are presented in Table 3.
Table 3.
The mean differences within-curcumin group at 3 months compared with baseline, means (S.E.)
| Mean score | Mean difference at 3 months compared with baseline |
P-value | 95% CI |
|---|---|---|---|
| Pain at rest | 1.37 ± 0.64 | 0.032* | [0.12, 2.62] |
| Pain at activity | 1.74 ± 0.73 | 0.017* | [0.32, 3.17] |
| Morning stiffness | 1.31 ± 0.70 | 0.061 | [−0.06, 2.68] |
| DASH | 11.84 ± 5.88 | 0.044* | [0.31, 23.37] |
| Right hand grip | 0.99 ± 0.82 | 0.229 | [−0.62, 2.59] |
| Left hand grip | 0.35 ± 0.83 | 0.671 | [−1.27, 1.98] |
| Right pinch strength | 0.24 ± 0.35 | 0.5 | [−0.45, 0.92] |
| Left pinch strength | 0.33 ± 0.35 | 0.94 | [−0.36, 1.01] |
DASH Disabilities of the arm, shoulder, and hand
*statistical significant
Safety parameter
One patient in the curcumin group experienced a gastrointestinal side effect (severe dyspepsia) after one week of curcumin treatment, resulting in withdrawal from the study. No other adverse effects were reported by the remaining patients. There were no significant changes in laboratory data, including white blood cell count, creatinine, electrolytes, liver function tests, erythrocyte sedimentation rate, and C-reactive protein, across patients in both groups. These results are summarised in Table 4.
Table 4.
Laboratory, mean (S.E.) changes over time
| Mean | Baseline | At 1 month | At 3 months | At 6 months | ||||
|---|---|---|---|---|---|---|---|---|
| Placebo | Curcumin | Placebo | Curcumin | Placebo | Curcumin | Placebo | Curcumin | |
| WBC | 6581.54 ± 395.30 |
6602.31 ± 395.30 |
6855.39 ± 395.30 |
6157.04 ± 403.60 |
7049 ± 419.62 |
5549.51 ± 431.21 | 6764.71 ± 441.28 | 5969.25 ± 443.06 |
| ESR | 27.85 ± 4.39 | 32.08 ± 4.39 | 23.54 ± 4.39 | 28.11 ± 4.45 | 26.32 ± 4.58 | 33.33 ± 4.67 | 24.99 ± 4.74 | 35.04 ± 4.76 |
| CRP | 2.09 ± 0.92 | 3.72 ± 0.92 | 1.65 ± 0.92 | 1.74 ± 0.96 | 1.96 ± 1.05 | 2.34 ± 1.10 | 2.26 ± 1.17 | 5.81 ± 1.17 |
| Creatinine | 0.76 ± 0.04 | 0.72 ± 0.04 | 0.77 ± 0.04 | 0.74 ± 0.04 | 0.77 ± 0.04 | 0.74 ± 0.04 | 0.77 ± 0.04 | 0.75 ± 0.04 |
| GFR | 86.63 ± 3.73 | 88.64 ± 3.73 | 85.18 ± 3.73 | 86.62 ± 3.75 | 86.24 ± 3.80 | 86.75 ± 3.84 | 85.63 ± 3.87 | 85.73 ± 3.88 |
| AST | 23.54 ± 1.56 | 25.46 ± 1.56 | 23.69 ± 1.56 | 23.87 ± 1.61 | 23.80 ± 1.70 | 28.12 ± 1.76 | 21.13 ± 1.82 | 25.89 ± 1.83 |
| ALT | 22.54 ± 2.08 | 20.77 ± 2.08 | 23.31 ± 2.08 | 18.70 ± 2.14 | 20.84 ± 2.25 | 23.25 ± 2.33 | 20.57 ± 2.41 | 20.26 ± 2.42 |
| ALP | 77.31 ± 3.78 | 75.54 ± 3.78 | 81.85 ± 3.78 | 71.88 ± 3.84 | 76.42 ± 3.96 | 71.26 ± 4.04 | 77.73 ± 4.11 | 72.95 ± 4.13 |
| GGT | 25.69 ± 3.05 | 23.31 ± 3.05 | 22.23 ± 3.05 | 21.55 ± 3.13 | 24.38 ± 3.27 | 26.96 ± 3.37 | 23.31 ± 3.47 | 24.05 ± 3.48 |
| TB | 0.62 ± 0.08 | 0.63 ± 0.08 | 0.63 ± 0.08 | 0.62 ± 0.08 | 0.69 ± 0.09 | 0.73 ± 0.09 | 0.59 ± 0.09 | 0.76 ± 0.09 |
| DB | 0.24 ± 0.03 | 0.23 ± 0.03 | 0.24 ± 0.03 | 0.21 ± 0.03 | 0.25 ± 0.03 | 0.26 ± 0.03 | 0.21 ± 0.03 | 0.28 ± 0.03 |
WBC White blood cell, ESR Erythrocyte sedimentation rate, CRP C-reactive protein, GFR Glomerular filtration rate, AST Aspartate transaminase, ALT Alanine transaminase, ALP Alkaline phosphatase, GGT Gamma-glutamyl transferase, TB Total bilirubin, DB Direct bilirubin
Discussion
The role of pro-inflammatory cytokines in the early stages of osteoarthritis is well recognised. The production of IL-1 and tumour necrosis factor, and the subsequent activation and release of metalloproteases, lead to cartilage damage and reactive or inflammatory changes in the synovium. Curcumin has been shown to mitigate these processes by reducing serum levels of inflammatory mediators, modulating inflammatory signalling pathways, and inhibiting chondrocyte apoptosis in animal osteoarthritis study [31–35]. A recent meta-analysis supports the use of oral curcumin for pain relief in knee osteoarthritis, demonstrating comparable efficacy at both low and high doses, with curcumin recommended as an adjunctive treatment [21]. Based on this evidence, we hypothesised that curcumin would be similarly effective in treating hand osteoarthritis as a symptomatic slow-acting drug.
To the best of our knowledge, this is the first double-blind, randomised, placebo-controlled trial to evaluate the efficacy of curcumin in hand osteoarthritis. Although this is a pilot study, our data have suggested promising outcomes. Patients receiving curcumin experienced reductions in VAS pain scores and improvements in DASH scores at 1 month, although statistical significance was not yet observed. However, by 3 months, the cumulative effect of curcumin resulted in significant reductions in both VAS pain at rest and during activity, when compared to the baseline and the placebo group. DASH scores also improved significantly at 3 months in the curcumin group, further supporting its therapeutic potential. Importantly, curcumin was well tolerated by the majority of participants, and laboratory tests confirmed its safety regarding liver and renal function. These findings are consistent with previous studies [36, 37] on knee osteoarthritis, which have demonstrated both the safety and efficacy of curcumin. The possible clinical implication of the present findings is that curcumin can improve patient outcomes in hand osteoarthritis.
However, one patient in the curcumin group experienced severe dyspepsia, which led to withdrawal from the study. While this side effect warrants caution, existing literature presents a more nuanced perspective. Some studies, such as that by Panahi et al., have indicated that curcumin may actually alleviate dyspepsia symptoms [38]. Additionally, Kongkam et al. found curcumin to be comparable to omeprazole in the treatment of functional dyspepsia, without any serious adverse effects [39]. Minor side effects such as diarrhea, headache, itching, rash, and yellow stool reported in other studies at higher doses [36, 40] were not observed in our study, likely due to the relatively low dosage of curcumin administered.
A key strength of our study was the daily monitoring of VAS scores through patient-maintained diary records, which minimised recall bias. Additionally, we utilized a mixed-effects model to assess both the effects of curcumin and changes over time, enhancing the robustness of our analysis. Another important feature was the monitoring of rescue drug use (Acetaminophen and Naproxen) across the groups at 1, 3 and 6 months, with no significant differences observed, allowing us to better isolate the effects and safety profiles of curcumin.
Despite these strengths, our study has limitations. This was a pilot trial with a reduced sample size due to difficulties in recruiting research participants. While our findings were statistically significant, a larger sample size is necessary for a definitive study. Furthermore, the inclusion of a wash-out period after 3 months of drug administration enabled us to observe that both VAS and DASH scores returned to baseline by the 6-month mark, suggesting that curcumin’s benefits are dependent on continued administration. This highlights the need for future studies to explore the long-term efficacy of curcumin in managing hand osteoarthritis symptoms.
Conclusion
The administration of low-dose oral curcumin over a 3-month period demonstrated significant improvements in pain reduction and hand function in patients with hand osteoarthritis. While the potential for dyspepsia should be considered, no severe adverse events were recorded, and curcumin was found to be safe overall. These findings suggest that curcumin is a viable alternative treatment option for hand osteoarthritis, meriting further investigation in a full-scale clinical trial.
Acknowledgements
Nattaphong Rattanavirotkul, Ph.D. proofread the manuscript.Chaophraya Abhaibhubejhr Hospital for their assistance in providing the experimental drug in this study.
Abbreviations
- BMI
Body mass index
- DASH
Disabilities of the Arm, Shoulder, and Hand
- GI
Gastrointestinal
- NSAIDs
Non-steroidal anti-inflammatory drugs
- VAS
Visual analogue scales
Authors’ contributions
Panithan Tuntiyatorn is the first author in this study. Tulyapruek Tawonsawatruk is the corresponding author in this study.P.T., C.L. and T.T created conceptualization and study design. C.L., and T.T conducted experiment and data curation.T.T. contributed data analysis.P.T. and C.L. prepared original draft preparation.P.T., C.L. T.K., I.W., and T.T writing-review and editingAll authors reviewed the manuscript.
Funding
Open access funding provided by Mahidol University. Ramathibodi Hospital, Mahidol University.
Data availability
The datasets generated and/or analysed during the current study are available from the corresponding author upon reasonable request to ensure compliance with ethical and privacy considerations.
Declarations
Ethics approval and consent to participate
The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of Mahidol university, Human research ethics committee, Faculty of medicine Ramathibodi hospital, Mahidol university. Protocol code COA. MURA2021/763, date of approval 14 September 2021. The trial has been registered in the Thai Clinical Trials Registry(TCTR) database. The identification number is TCTR20210929003. Informed consent was obtained from all subjects involved in the study.
Consent for publication
The authors affirm that human research participants provided informed consent for publication.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Marshall M, et al. Hand osteoarthritis: clinical phenotypes, molecular mechanisms and disease management. Nat Rev Rheumatol. 2018;14(11):641–56. [DOI] [PubMed] [Google Scholar]
- 2.Kroon FPB, et al. Efficacy and safety of non-pharmacological, pharmacological and surgical treatment for hand osteoarthritis: a systematic literature review informing the 2018 update of the EULAR recommendations for the management of hand osteoarthritis. RMD Open. 2018;4(2):e000734. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Kolasinski SL, et al. American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Rheumatol. 2019;72(2):220–33. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Harirforoosh S, Asghar W, Jamali F. Adverse effects of nonsteroidal antiinflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications. J Pharm Pharm Sci. 2013;16(5):821–47. [DOI] [PubMed] [Google Scholar]
- 5.Pintatum A, et al. In vitro anti-inflammatory, anti-oxidant, and cytotoxic activities of four curcuma species and the isolation of compounds from curcuma aromatica rhizome. Biomolecules. 2020. 10.3390/biom10050799. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Chin K-Y. The spice for joint inflammation: anti-inflammatory role of curcumin in treating osteoarthritis. Drug Des Devel Ther. 2016. 10.2147/DDDT.S117432. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Shakibaei M, et al. Suppression of NF-kappaB activation by Curcumin leads to Inhibition of expression of cyclo-oxygenase-2 and matrix metalloproteinase-9 in human articular chondrocytes: implications for the treatment of osteoarthritis. Biochem Pharmacol. 2007;73(9):1434–45. [DOI] [PubMed] [Google Scholar]
- 8.Swallow J, Seidler K, Barrow M. The mechanistic role of curcumin on matrix metalloproteinases in osteoarthritis. Fitoterapia. 2024;174:105870. [DOI] [PubMed] [Google Scholar]
- 9.Wang J, et al. Regulation of type II collagen, matrix metalloproteinase-13 and cell proliferation by interleukin-1β is mediated by curcumin via inhibition of NF-κB signaling in rat chondrocytes. Mol Med Rep. 2017;16(2):1837–45. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Henrotin Y, et al. Biological actions of curcumin on articular chondrocytes. Osteoarthritis Cartilage. 2010;18(2):141–9. [DOI] [PubMed] [Google Scholar]
- 11.Zhang R, et al. Curcumin supplementation enhances bone marrow mesenchymal stem cells to promote the anabolism of articular chondrocytes and cartilage repair. Cell Transplant. 2021;30:0963689721993776. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Zhou Y, et al. Chemically modified curcumin (CMC2.24) alleviates osteoarthritis progression by restoring cartilage homeostasis and inhibiting chondrocyte apoptosis via the NF-κB/HIF-2α axis. J Mol Med (Berl). 2020;98(10):1479–91. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Feng K, et al. Curcumin inhibits the PERK-eIF2α‐CHOP pathway through promoting SIRT1 expression in oxidative stress‐induced rat chondrocytes and ameliorates osteoarthritis progression in a rat model. Oxidative Med Cell Longev. 2019;2019(1):8574386. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Jin Z, et al. Curcumin exerts chondroprotective effects against osteoarthritis by promoting AMPK/PINK1/Parkin-mediated mitophagy. Biomed Pharmacother. 2022;151:113092. [DOI] [PubMed] [Google Scholar]
- 15.Yao J, et al. Curcumin-Alleviated Osteoarthritic progression in rats fed a High-Fat diet by inhibiting apoptosis and activating autophagy via modulation of MicroRNA-34a. J Inflamm Res. 2021;14:2317–31. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Daily JW, Yang M, Park S. Efficacy of turmeric extracts and Curcumin for alleviating the symptoms of joint arthritis: A systematic review and Meta-Analysis of randomized clinical trials. J Med Food. 2016;19(8):717–29. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Bannuru RR, et al. Efficacy of curcumin and Boswellia for knee osteoarthritis: systematic review and meta-analysis. Semin Arthritis Rheum. 2018;48(3):416–29. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Onakpoya IJ, et al. Effectiveness of curcuminoids in the treatment of knee osteoarthritis: a systematic review and meta-analysis of randomized clinical trials. Int J Rheum Dis. 2017;20(4):420–33. [DOI] [PubMed] [Google Scholar]
- 19.Soleimani V, Sahebkar A, Hosseinzadeh H. Turmeric (Curcuma longa) and its major constituent (curcumin) as nontoxic and safe substances. Rev Phytother Res. 2018;32(6):985–95. [DOI] [PubMed] [Google Scholar]
- 20.Zeng L, et al. The efficacy and safety of curcuma longa extract and curcumin supplements on osteoarthritis: a systematic review and meta-analysis. Biosci Rep. 2021. 10.1042/BSR20210817. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Hsiao AF, et al. The efficacy of high- and low-dose curcumin in knee osteoarthritis: a systematic review and meta-analysis. Complement Ther Med. 2021;63:102775. [DOI] [PubMed] [Google Scholar]
- 22.Altman R, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand. Arthritis Rheum. 1990;33(11):1601–10. [DOI] [PubMed] [Google Scholar]
- 23.Tongprasert S, Rapipong J, Buntragulpoontawee M. The cross-cultural adaptation of the DASH questionnaire in Thai (DASH-TH). J Hand Ther. 2014;27(1):49–54. [DOI] [PubMed] [Google Scholar]
- 24.Ezzati F, Pezeshk P. Radiographic findings of inflammatory arthritis and mimics in the hands. Diagnostics. 2022. 10.3390/diagnostics12092134. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Lancaster GA, Thabane L. Guidelines for reporting non-randomised pilot and feasibility studies. Pilot Feasibility Stud. 2019;5(1):114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Eldridge SM, et al. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016;355:i5239. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharm Statistics: J Appl Stat Pharm Ind. 2005;4(4):287–91. [Google Scholar]
- 28.Lancaster GA, Dodd S, Williamson PR. Design and analysis of pilot studies: recommendations for good practice. J Eval Clin Pract. 2004;10(2):307–12. [DOI] [PubMed] [Google Scholar]
- 29.Teare MD, et al. Sample size requirements to estimate key design parameters from external pilot randomised controlled trials: a simulation study. Trials. 2014;15:264. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Browne RH. On the use of a pilot sample for sample size determination. Stat Med. 1995;14(17):1933–40. [DOI] [PubMed] [Google Scholar]
- 31.Zeng L, et al. Efficacy and safety of curcumin and curcuma longa extract in the treatment of arthritis: a systematic review and meta-analysis of randomized controlled trial. Front Immunol. 2022;13:891822. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Shang W, et al. Curcumin inhibits osteoclastogenic potential in PBMCs from rheumatoid arthritis patients via the suppression of MAPK/RANK/c-Fos/NFATc1 signaling pathways. Mol Med Rep. 2016;14(4):3620–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Manca ML, et al. Potential therapeutic effect of Curcumin loaded hyalurosomes against inflammatory and oxidative processes involved in the pathogenesis of rheumatoid arthritis: the use of fibroblast-like synovial cells cultured in synovial fluid. Eur J Pharm Biopharm. 2019;136:84–92. [DOI] [PubMed] [Google Scholar]
- 34.Zhang Z, et al. Curcumin slows osteoarthritis progression and relieves osteoarthritis-associated pain symptoms in a post-traumatic osteoarthritis mouse model. Arthritis Res Ther. 2016;18(1):128. [DOI] [PMC free article] [PubMed] [Google Scholar] [Research Misconduct Found]
- 35.Yabas M, et al. A next generation formulation of Curcumin ameliorates experimentally induced osteoarthritis in rats via regulation of inflammatory mediators. Front Immunol. 2021;12:609629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Nakagawa Y, et al. The efficacy and safety of highly-bioavailable curcumin for treating knee osteoarthritis: a 6-month open-labeled prospective study. Clin Med Insights Arthritis Musculoskelet Disord. 2020;13:1179544120948471. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Panahi Y, et al. Curcuminoid treatment for knee osteoarthritis: a randomized double-blind placebo-controlled trial. Phytother Res. 2014;28(11):1625–31. [DOI] [PubMed] [Google Scholar]
- 38.Panahi Y, et al. Effect of Curcumin on severity of functional dyspepsia: a triple blinded clinical trial. Adv Exp Med Biol. 2021;1308:119–26. [DOI] [PubMed] [Google Scholar]
- 39.Kongkam P, et al. Curcumin and proton pump inhibitors for functional dyspepsia: a randomised, double blind controlled trial. BMJ Evidence-Based Med. 2023;28(6):399–406. [DOI] [PubMed] [Google Scholar]
- 40.Lao CD, et al. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med. 2006;6:10. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated and/or analysed during the current study are available from the corresponding author upon reasonable request to ensure compliance with ethical and privacy considerations.