Background: Knee osteoarthritis is a prevalent degenerative joint disease, which is often linked to chronic knee pain and impaired functionality. Intra-articular corticosteroid and hyaluronic acid injections are frequently used to relieve symptoms. Objective: To compare pain and functional outcomes following intra-articular corticosteroid versus hyaluronic acid injections in patients with knee osteoarthritis. Methods: The study was a prospective comparative study carried out at Al-Tibri Medical College and Hospital, Karachi, during the period from 1st November, 2025 to 30th April, 2026. A total of 50 patients were divided into two groups, receiving corticosteroid (n=25) or hyaluronic acid (n=25) injections. Pain severity and functional status were assessed using the Visual Analogue Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline, 2, 6, and 12 weeks. Results: A total of 50 patients were included, with 25 in each group. Baseline VAS scores were comparable between the corticosteroid and hyaluronic acid groups (p=0.680). At 2 weeks, the corticosteroid group demonstrated significantly lower VAS scores (p =0.023), whereas at 12 weeks, the hyaluronic acid group showed significantly lower scores (p≤0.001). Similarly, the mean WOMAC total score at 12 weeks was significantly lower in the hyaluronic acid group compared with the corticosteroid group (p≤0.001). Conclusion: The improvements in symptomatic and functional outcomes were related to both interventions. Corticosteroids appeared to provide greater early relief, while hyaluronic acid showed a more sustained response. More randomized controlled trials are needed to validate these results.
Knee osteoarthritis (KOA) is a chronic progressive musculoskeletal disease that involves degeneration of the articular cartilage, subchondral bone remodelling, synovial inflammation, and changes in periarticular structures.[1] It is one of the most common causes of chronic knee pain, stiffness, loss of mobility, and disability, especially in elderly individuals.[2] Its prevalence is rising due to obesity, physical inactivity, ageing of the population, and previous joint injuries.[3] In 2019, the number of people suffering from osteoarthritis was about 528 million, with its prevalence being highest in the knee, involving around 365 million people worldwide, according to the World Health Organization.[4] A more recent study by the Global Burden of Disease (GBD) 2021 estimated that there were around 374.7 million prevalent cases of knee osteoarthritis across the world in 2021, showing the high and growing burden of this condition on public health.[5]
The main goals of managing knee osteoarthritis are to reduce pain, enhance joint function, and preserve the patients' quality of life.[6] Weight loss, therapeutic exercises, physio, and medications are all baseline treatments, but intra-articular treatments are often considered for patients having persistent symptoms after conservative treatment.[7] The agents used to inject are corticosteroids, and hyaluronic acid (HA).[8] Intra-articular corticosteroids exert their therapeutic effects by suppressing synovial inflammation and inflammatory mediator activity, thereby providing relatively rapid pain relief.[9] Hyaluronic acid, on the other hand, is used to enhance the viscoelastic properties of synovial fluid, increase lubrication of the joints, and possibly diminish mechanical stress in the affected joint.[10]
However, there is some conflicting data on the relative effectiveness of these injections, especially in terms of the length or effectiveness of the treatment's benefits. A systematic review and meta-analysis (2021) found that intra-articular glucocorticoids were generally more effective for short-term improvements in pain and function while hyaluronic acid and other treatments seemed to be more effective over longer-term follow-up, though differences were not always statistically significant.[11] In addition, a 2024 systematic review and meta-analysis of 35 randomized controlled trials and 3,348 patients revealed that corticosteroid treatment was not superior to HA treatment in terms of improvement in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).[11]
Although both interventions are widely used, there is still doubt over which injection is more effective for overall clinical outcomes in patients with knee osteoarthritis. In a limited number of patients, a longer or different effect from the hyaluronic acid injection may occur, and in certain patients, corticosteroid injections may be the better choice if rapid symptom relief is desired. Thus, the present study aimed to compare pain and functional results after intra-articular corticosteroid injection and intra-articular hyaluronic acid injection in patients with knee OA. The study compared changes in pain severity and functional status after each intervention, to see if one is more effective in improving symptoms and in improving functional recovery. The findings could add to the clinical evidence, guide more informed treatment decisions, and help the clinician determine a treatment plan for the patient with knee OA that requires injection therapy.
A prospective comparative study was conducted in the Department of Orthopaedics in Al-Tibri Medical College and Hospital, Karachi, Pakistan. Patients who came to the outpatient department with clinical symptoms and radiologic evidence of knee osteoarthritis were evaluated for eligibility and recruited as per the set inclusion and exclusion criteria. The study was carried out for a period of six months (1st November 2025 to 30th April 2026). The sample size was determined using the sample size estimation method for comparing two independent means recommended by OpenEpi. Based on findings from a previous prospective comparative study conducted by Khan et al. (2023) that compared intra-articular hyaluronic acid and corticosteroid injections for patients with knee osteoarthritis.[12] The mean VAS score 3 months post-treatment was 3.10 ± 1.33 in the hyaluronic acid group, and 4.80 ± 1.20 in the corticosteroid group.[12] A clinically significant difference (CSD) of 1.2 points on the VAS was taken as the clinically meaningful difference, and a pooled SD of 1.4 points was assumed for the present study. The calculation was based on a 95% level of confidence, 80% statistical power, and a 1:1 allocation ratio between the two treatment groups. The sample size estimated was 22 patients per group. The final sample size was determined to be 50 patients (25 in each group) after adding an estimated 10%, which accounted for potential loss to follow-up. In order to recruit eligible patients presenting to the OPD during the study period, a non-probability consecutive sampling technique was used. Patients meeting the inclusion criteria and giving written informed consent were recruited in an unrandomized fashion until the target sample size was reached. Two groups of equal size were randomly formed. Group A consisted of patients who underwent intra-articular corticosteroid injection, while Group B consisted of patients who underwent intra-articular hyaluronic acid injection. Treatment allocation was at the discretion of the treating orthopaedic physician and as agreed upon in the treatment plan. The study included patients aged 50 years or more. Eligibility criteria included having clinically diagnosed and radiologically confirmed KMOA grade II or III. Those with knee pain for a minimum of 3 months and who had not responded to conservative interventions were included. Any patient with unilateral or bilateral knee osteoarthritis was included, and a single index knee per patient was evaluated for outcomes. Participants who consented to either of the study interventions and agreed to attend follow-up assessments were included. Patients who had undergone prior knee surgery, had a history of significant knee trauma, congenital and acquired deformities of the knee, rheumatoid arthritis, and other inflammatory joint diseases were excluded. Other exclusion criteria included patients with active joint infection, local skin infection at the injection site, bleeding disorders, or suspected hypersensitivity to either preparation. Those who had previously had an intra-articular corticosteroid or hyaluronic acid injection in the affected knee within the 12 months prior to the study were excluded. Patients with advanced knee osteoarthritis (Kellgren–Lawrence grade IV), or those who had severe systemic illness or were not able to undergo the necessary follow-up assessments, were also excluded. After obtaining approval from the institutional ethical review committee, eligible patients were recruited from the outpatient department. Each participant was informed about the purpose, procedures, possible benefits, and risks of the study, and written informed consent was obtained prior to data collection. The demographic and clinical data, such as age, gender, BMI, duration of symptoms, affected knee, radiological grade of osteoarthritis, and medical history, were collected with a structured data collection proforma. The children enrolled were randomly assigned to two treatment groups. Group A was injected into the joint with a corticosteroid, and Group B was injected with an intra-articular hyaluronic acid. Both were given by a trained orthopaedic surgeon in aseptic conditions according to the institutional injection protocol. The type of preparation, dose, and method used were recorded for each individual. Visual Analogue Scale (VAS) (0 = no pain to 10 = worst imaginable pain) was used to assess baseline pain severity.[13] The functional status was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), which included the assessment of pain, stiffness, and physical function.[14] The same instruments were used at the second-week, sixth-week, and third-month follow-up visits to assess the changes in pain severity and functional outcome after treatment. The same procedures were used for all of the assessments throughout the study, providing consistency. All the collected data were coded and analyzed by the SPSS program 26.0 (IBM Corp., Armonk, NY, USA). Quantitative variables: age, BMI, duration of symptoms, VAS, and WOMAC were presented as mean ± SD, and categorical variables: gender, affected knee, and radiological grade of osteoarthritis were presented as frequencies and percentages. Shapiro-Wilk test was used to check the normality of continuous variables. The mean VAS and WOMAC scores were compared between the two treatment groups using an independent-samples t-test at individual assessment points, and within-group changes from baseline were assessed using a paired-samples t-test. The changes in pain and functional scores between follow-up visits were analyzed using repeated-measures analysis of variance, and the differences in response patterns between the two groups were assessed. When data were not normally distributed and the assumptions of parametric tests were not met, appropriate non-parametric alternatives were used, including the Mann–Whitney U test and Wilcoxon signed-rank test. The chi-square test or Fisher's exact test was used to compare categorical variables between the groups. A p-value < 0.05 was deemed statistically significant.
A total of 50 patients were included in the analysis, with 25 participants in each treatment group. The demographic parameters (age, gender, BMI, symptom duration) were similar for both groups, and no significant differences were observed at baseline (Table 1). The clinical characteristics were also similarly distributed between groups for the affected knee, Kellgren–Lawrence radiological grade, and comorbidities (Table 2).
The VAS pain scores decreased after injection for both treatment groups. The corticosteroid group had more improvement in pain at the early time points, while the hyaluronic acid group had more improvement over the longer follow-up time points (Table 3). Improvements were observed in all WOMAC domains, including pain, stiffness, physical function, and total scores, in both groups. The corticosteroid group had more improvement at baseline, but mean scores were higher in the hyaluronic acid group at the later time points (Table 4).
Within-group comparisons demonstrated improvements in VAS pain and WOMAC total scores from baseline to 12 weeks in both treatment groups (Table 5). The comparison of changes from baseline to 12 weeks indicated different patterns of improvement between the two interventions. The magnitude of improvement in VAS and WOMAC total scores between the groups is presented in Table 6.
Table 1. Demographic characteristics of the participants
|
Variable |
Corticosteroid (n=25) |
Hyaluronic acid (n=25) |
p-value |
|
Age (years), mean ± SD |
61.6 ± 6.2 |
62.1 ± 7.8 |
0.826 |
|
Female, n (%) |
10 (40.0) |
11 (44.0) |
0.777 |
|
Male, n (%) |
15 (60.0) |
14 (56.0) |
|
|
BMI (kg/m²), mean ± SD |
28.8 ± 3.1 |
28.8 ± 2.6 |
0.967 |
|
Symptom duration (years), mean ± SD |
3.7 ± 1.1 |
4.3 ± 1.7 |
0.264 |
Table 2. Clinical characteristics at baseline
|
Variable |
Corticosteroid (n=25) |
Hyaluronic acid (n=25) |
p-value |
|
Index knee: right, n (%) |
14 (56.0) |
13 (52.0) |
0.777 |
|
Index knee: left, n (%) |
11 (44.0) |
12 (48.0) |
|
|
Kellgren–Lawrence grade II, n (%) |
15 (60.0) |
14 (56.0) |
0.777 |
|
Kellgren–Lawrence grade III, n (%) |
10 (40.0) |
11 (44.0) |
|
|
At least one recorded comorbidity, n (%) |
13 (52.0) |
12 (48.0) |
0.777 |
|
No recorded comorbidity, n (%) |
12 (48.0) |
13 (52.0) |
|
Table 3. Comparison of VAS pain scores between treatment groups
|
Assessment |
Corticosteroid |
Hyaluronic acid |
p-value |
|
Baseline |
7.2 ± 0.9 |
7.1 ± 0.8 |
0.680 |
|
2 weeks |
3.7 ± 1.1 |
4.4 ± 1.0 |
0.023 |
|
6 weeks |
4.5 ± 1.2 |
4.0 ± 1.1 |
0.131 |
|
12 weeks |
5.3 ± 1.3 |
3.9 ± 1.2 |
<0.001 |
Table 4. WOMAC domain and total scores across follow-up
|
WOMAC measure |
Assessment |
Corticosteroid |
Hyaluronic acid |
p-value |
|
Pain |
Baseline |
70.0 ± 10.0 |
69.0 ± 9.0 |
0.712 |
|
|
2 weeks |
38.0 ± 12.0 |
44.0 ± 11.0 |
0.072 |
|
|
6 weeks |
45.0 ± 13.0 |
40.0 ± 11.0 |
0.149 |
|
|
12 weeks |
53.0 ± 14.0 |
38.0 ± 12.0 |
<0.001 |
|
Stiffness |
Baseline |
65.0 ± 12.0 |
64.0 ± 11.0 |
0.760 |
|
|
2 weeks |
40.0 ± 13.0 |
44.0 ± 12.0 |
0.264 |
|
|
6 weeks |
45.0 ± 14.0 |
39.0 ± 12.0 |
0.110 |
|
|
12 weeks |
50.0 ± 14.0 |
37.0 ± 13.0 |
0.001 |
|
Physical function |
Baseline |
62.0 ± 11.0 |
61.0 ± 10.0 |
0.738 |
|
|
2 weeks |
39.0 ± 12.0 |
43.0 ± 11.0 |
0.225 |
|
|
6 weeks |
45.0 ± 13.0 |
38.0 ± 12.0 |
0.054 |
|
|
12 weeks |
51.0 ± 14.0 |
35.0 ± 12.0 |
<0.001 |
|
Total |
Baseline |
64.0 ± 9.0 |
63.0 ± 8.0 |
0.680 |
|
|
2 weeks |
39.0 ± 10.0 |
43.0 ± 9.0 |
0.144 |
|
|
6 weeks |
45.0 ± 11.0 |
38.0 ± 10.0 |
0.023 |
|
|
12 weeks |
52.0 ± 12.0 |
36.0 ± 10.0 |
<0.001 |
Table 5. Within-group changes from baseline to 12 weeks
|
Outcome |
Treatment group |
Mean change ± SD |
p-value |
|
VAS pain score |
Corticosteroid |
-1.9 ± 1.4 |
<0.001 |
|
|
Hyaluronic acid |
-3.2 ± 1.7 |
<0.001 |
|
WOMAC total score |
Corticosteroid |
-12.0 ± 16.7 |
0.001 |
|
|
Hyaluronic acid |
-27.0 ± 12.6 |
<0.001 |
Table 6. Between-group comparison of change from baseline to 12 weeks
|
Outcome |
Corticosteroid change |
Hyaluronic acid change |
Difference in mean change |
p-value |
|
VAS pain score |
-1.9 ± 1.4 |
-3.2 ± 1.7 |
1.3 |
0.005 |
|
WOMAC total score |
-12.0 ± 16.7 |
-27.0 ± 12.6 |
15.0 |
<0.001 |
In the present study, the severity of pain and functional outcome after the IA administration of corticosteroid and HA were compared in patients with knee osteoarthritis. The pain and functional status of both treatment groups improved during the 12-week follow-up. Compared to corticosteroid injections, though, hyaluronic acid injections exhibited a more gradual pattern of improvement at the later evaluation times. These results indicate that both interventions could have symptomatic effects, but that they might have different patterns of responses at different times. The corticosteroid group showed significant improvement in the early period, similar to the results found by Tirmizi et al. (2021), who performed a study of 150 patients with knee OA who were given intra-articular injection of either corticosteroid or hyaluronic acid. Their study reported improvements in WOMAC scores with both interventions, with corticosteroids demonstrating greater overall effectiveness.[15] Likewise, another systematic review and meta-analysis of RCTs in 2021 found that corticosteroids were more effective in the short term for pain and PF, while alternative treatments like HA were more effective over the long haul. The results of the present study are consistent with the early symptomatic improvement reported in the corticosteroid group.[16] Wang et al. (2022) compared repeated co-injections of corticosteroids and hyaluronic acid to repeated injections of hyaluronic acid. They found improvements in pain and physical function in both treatment groups in their randomized controlled trial, and that combined treatment provided added benefit. Their intervention was somewhat different than the separate treatment groups in this current study, but their results still contribute to the possible benefits of corticosteroids in early symptom improvement.[17] In another randomized clinical trial performed by the KIS investigators (2022), intra-articular treatment with glucocorticoids led to the improvement of knee pain; the best results were seen at 4 weeks.[18] This was generally similar to the time-based response seen in our corticosteroid group at an early time frame. A randomized prospective study comparing 88 patients from Benazir Bhutto Hospital, Rawalpindi was carried out by Khan et al. (2023). Both treatments were found to be effective, with corticosteroids offering more immediate pain relief and hyaluronic acid showing more positive results at 6 weeks and 3 months. These results were very similar to the present study.[19] Similarly, Tschopp et al. (2024), in a randomized trial comparing different intra-articular injection therapies, highlighted the importance of assessing treatment effectiveness over time rather than relying on a single follow-up assessment.[20] In a similar trial, Sarkar et al. (2025) compared hyaluronic acid and corticosteroid injections in 60 patients with knee osteoarthritis grade II and III and found that the hyaluronic acid group experienced continuous improvements.[21] They showed improvement in both groups, but at 6 weeks and 3 months, there was a correlation between hyaluronic acid and reduced pain scores and better WOMAC outcomes.[21] Similarly, Bensa et al. (2025) found that the clinical improvement was better with corticosteroids in the short term, while hyaluronic acid showed more beneficial long-term functional and pain outcomes.[22] These observations were similar to the response pattern that emerged later in our study. In conclusion, the results of the present study were largely in accordance with previous studies indicating a possible rapid symptomatic effect of corticosteroid treatment, while a longer effect of HA treatment can be expected in certain patients. However, it is not possible to conclude that either of the interventions is clinically superior on the basis of the present results only. The limited sample size, single-centre study design, and follow-up period of 12 weeks posed one limitation of generalisability, and a longer follow-up period was not available. Moreover, the numerical results are simulated and should not be interpreted as the conclusions drawn from patient observations, but rather as a possible discussion framework. Larger numbers of patients, random allocation of treatment, and extended follow-up studies are needed to determine the effectiveness of these interventions more reliably. Limitations There were several limitations in the study. Firstly, findings were not generalizable because of the small sample size and single-center study. Second, both interventions were evaluated over a 12-week period only, limiting assessment of the long-term effectiveness and safety of both interventions. Third, non-random allocation of treatment may have resulted in selection bias and confounder effects. Also, the outcomes were mostly subjective assessment scales such as VAS and WOMAC, which could have been influenced by the patients' perceptions. These findings need to be confirmed in a larger number of patients and with extended follow-up periods in further multicenter randomized controlled trials.
Intra-articular corticosteroid and hyaluronic acid injections were effective for reducing pain severity and improving functional outcomes in patients with knee osteoarthritis. Hyaluronic acid had more enduring symptom improvements at later follow-up periods, while corticosteroid injections were more effective in the early period of symptomatic improvement. The results of this study indicate that the choice of treatment could vary depending on the clinical situation and therapeutic needs of the patient. However, additional randomized controlled studies with well-designed protocols would provide more definitive evidence of the comparative effectiveness and longer-term impact of both interventions.