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Research Article | Volume 17 Issue 11 (None, 2025) | Pages 1 - 5
A Prospective Randomized Study Comparing Platelet-Rich Plasma and Hyaluronic Acid Injections for Pain and Functional Outcomes in Degenerative Shoulder Arthritis
 ,
 ,
1
Assistant Professor, Department of Orthopedics, Bharatratna Atalbihari Vajpayee Medical, College, Pune‐411011, India
2
Associate Professor & HOD, Department of Orthopedics, Govt Medical College, Sindhudurg-416812, India
3
Consultant Orthopedic Surgeon, Dhage Orthopedic Spine Clinic, Akola 444001, India.
Under a Creative Commons license
Open Access
Received
Sept. 16, 2025
Revised
Oct. 10, 2025
Accepted
Nov. 5, 2025
Published
Nov. 6, 2025
Abstract

Background: Degenerative shoulder arthritis leads to chronic pain and functional limitation. Intra-articular biologic therapies such as platelet-rich plasma (PRP) and hyaluronic acid (HA) have gained increasing attention as joint-preserving alternatives to corticosteroid injections and surgery. This study aimed to compare the efficacy of PRP and HA injections in improving pain and shoulder function in patients with degenerative shoulder arthritis. Methods: A total of 70 patients diagnosed with degenerative shoulder arthritis were prospectively enrolled and randomized into two groups: Group A received PRP (n=35) and Group B received HA (n=35) intra-articular injections under ultrasound guidance. Pain and functional outcomes were assessed using the Visual Analogue Scale (VAS) and Constant-Murley Shoulder Score at baseline, 4, 12, and 24 weeks. Data were analyzed using Student’s t-test, chi-square test, and repeated-measures ANOVA, with a significance level of p<0.05. Results: Baseline demographic and clinical characteristics were comparable between the two groups (p>0.05). The mean reduction in VAS from baseline to 24 weeks was significantly greater in the PRP group (−4.6 ± 1.1) compared to the HA group (−3.6 ± 1.2) (p=0.0003). Similarly, the mean increase in Constant-Murley score was higher in the PRP group (+30 ± 9) than in the HA group (+21 ± 10) (p<0.001). A higher proportion of PRP-treated patients achieved clinically significant improvement in both pain (85.7% vs. 62.9%; p=0.029) and function (77.1% vs. 54.3%; p=0.044). No serious adverse events were reported in either group. Conclusion: PRP injections were more effective than HA in reducing pain and enhancing functional recovery in patients with degenerative shoulder arthritis, with comparable safety. PRP thus represents a promising, biologically driven treatment option for patients seeking non-surgical management of shoulder arthritis.

Keywords
INTRDUCTION

Degenerative shoulder arthritis is a chronic, progressive condition characterized by the deterioration of articular cartilage, subchondral bone changes, and synovial inflammation, leading to pain, stiffness, and functional impairment. It most frequently affects older adults but may also occur in younger individuals due to repetitive microtrauma, prior injury, or instability. The shoulder joint, particularly the glenohumeral articulation, plays a critical role in upper limb mobility, and thus degeneration severely affects the quality of life and daily functioning. Traditional conservative management strategies include physiotherapy, oral analgesics, corticosteroid injections, and surgical interventions for advanced cases. However, concerns regarding the short duration of symptom relief and potential adverse effects of repeated corticosteroid use have driven interest toward biological and regenerative alternatives.[1]

Among emerging biological therapies, platelet-rich plasma (PRP) and hyaluronic acid (HA) injections have gained considerable attention as minimally invasive, joint-preserving options for osteoarthritic joints. PRP, derived from autologous blood centrifugation, is rich in platelets and growth factors such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-β). These bioactive molecules promote angiogenesis, cellular proliferation, and tissue regeneration, thereby reducing inflammation and stimulating cartilage repair. HA, on the other hand, is a naturally occurring glycosaminoglycan and a major component of synovial fluid that contributes to joint lubrication, shock absorption, and modulation of inflammatory responses. In osteoarthritic joints, decreased HA concentration and altered molecular weight lead to reduced viscoelastic properties and increased mechanical stress on cartilage surfaces. Exogenous HA supplementation aims to restore these properties, thereby improving joint biomechanics and pain relief.[2][3]

Although both PRP and HA have shown efficacy in various joint pathologies, including knee osteoarthritis, their comparative effectiveness in shoulder arthritis remains an area of ongoing research. Some studies have suggested that PRP provides more prolonged pain relief and functional improvement compared to HA due to its regenerative properties, whereas others have reported equivalent outcomes. The variability in PRP preparation protocols, injection techniques, and disease stages complicates the interpretation of existing evidence. A well-designed randomized comparative trial focusing specifically on degenerative shoulder arthritis is therefore warranted to establish relative efficacy and guide clinical decision-making.[4][5]

Aim:
To compare the efficacy of platelet-rich plasma (PRP) and hyaluronic acid (HA) injections in improving pain and functional outcomes in patients with degenerative shoulder arthritis.

 Objectives:

  1. To assess the reduction in pain scores following PRP and HA injections using the Visual Analogue Scale (VAS).
  2. To evaluate functional improvement using the Constant-Murley Shoulder Score at predefined follow-up intervals.
  3. To compare the overall clinical outcomes and safety profile between PRP and HA treatment groups.
MATERIAL AND METHODOLOGY

Source of Data: Patients diagnosed with degenerative shoulder arthritis attending the Orthopedics Outpatient Department and Physical Medicine Rehabilitation Unit at Bharatratna Atalbihari Vajpayee Medical College, Pune, were enrolled after obtaining ethical clearance and informed consent.

Study Design: This was a prospective, randomized, controlled, comparative interventional study.

Study Location: Department of Orthopedics, at Bharatratna Atalbihari Vajpayee Medical College, Pune.

Study Duration: The study was conducted over a period of 18 months from January 2023 to June 2024, including patient recruitment, intervention, and follow-up.

Sample Size: A total of 70 patients were included, randomly divided into two groups:

  • Group A: PRP injection group (n=35)
  • Group B: Hyaluronic acid injection group (n=35)

 Inclusion Criteria:

  • Patients aged 40–75 years with radiologically confirmed degenerative shoulder arthritis.
  • Patients with chronic shoulder pain (>3 months) refractory to conservative management.
  • Patients willing to provide informed consent and comply with follow-up.

 Exclusion Criteria:

  • Inflammatory arthropathies (rheumatoid arthritis, gout, etc.).
  • Shoulder infection, fracture, or prior surgery.
  • Coagulopathies or platelet disorders.
  • Use of anticoagulant or corticosteroid therapy within the last 4 weeks.
  • Uncontrolled diabetes or systemic illness precluding injection therapy.

 Procedure and Methodology: Patients were randomized into two groups using a computer-generated randomization table. In the PRP group, 20 mL of autologous venous blood was drawn into tubes containing acid-citrate-dextrose solution and centrifuged using a double-spin method (first at 1500 rpm for 10 minutes to separate plasma, followed by 3500 rpm for 10 minutes to concentrate platelets). Approximately 4 mL of PRP was aspirated and injected intra-articularly under aseptic conditions into the glenohumeral joint.

In the HA group, 2 mL of high molecular weight sodium hyaluronate (20 mg/mL) was injected intra-articularly under similar aseptic precautions. All injections were performed using ultrasound guidance with a posterior approach. Patients were advised relative rest for 24 hours, followed by supervised physiotherapy and range-of-motion exercises.

Sample Processing: PRP preparation and activation were performed under sterile conditions in a laminar flow hood. Platelet concentration was verified microscopically to ensure at least a 4–5-fold increase above baseline count before injection.

Data Collection: Pain and function were assessed using VAS and Constant-Murley Shoulder Scores at baseline, 4 weeks, 12 weeks, and 24 weeks. Adverse events were recorded throughout follow-up.

Statistical Methods: Data were entered in Microsoft Excel and analyzed using SPSS version 26. Quantitative data were expressed as mean ± SD and compared using unpaired t-tests or repeated measures ANOVA. Qualitative variables were analyzed using chi-square tests. A p-value <0.05 was considered statistically significant.

OBSERVATION AND RESULTS

OBSERVATION AND RESULTS

 

Table 1: Baseline profile and primary efficacy (N=70)

Measure

PRP (n=35)

HA (n=35)

Effect & Test of significance

95% CI

p-value

Age (years), Mean (SD)

61.9 (7.8)

62.6 (8.1)

Mean diff = −0.70; Welch t=−0.37

−4.48 to +3.08

0.713

Male sex, n (%)

18 (51.4)

19 (54.3)

RR = 0.95; χ²(1)=0.06

0.61 to 1.48

0.811

Symptom duration (months), Mean (SD)

16.2 (6.0)

15.8 (6.3)

Mean diff = +0.40; Welch t=0.27

−2.53 to +3.33

0.786

Dominant shoulder affected, n (%)

21 (60.0)

22 (62.9)

RR = 0.95; χ²(1)=0.06

0.66 to 1.38

0.806

Radiographic severity—Severe, n (%)

15 (42.9)

16 (45.7)

RR = 0.94; χ²(1)=0.06

0.55 to 1.59

0.810

Baseline VAS (0–10), Mean (SD)

7.4 (1.0)

7.3 (1.0)

Mean diff = +0.10; Welch t=0.42

−0.38 to +0.58

0.676

Baseline Constant score (0–100), Mean (SD)

42 (8)

43 (9)

Mean diff = −1.00; Welch t=−0.49

−5.05 to +3.05

0.623

Primary pain outcome: ΔVAS (baseline→24 w), Mean (SD)

−4.6 (1.1)

−3.6 (1.2)

Mean diff = −1.00; Welch t=−3.63

−1.55 to −0.45

0.0003

Primary function outcome: ΔConstant (baseline→24 w), Mean (SD)

+30 (9)

+21 (10)

Mean diff = +9.00; Welch t=3.96

+4.47 to +13.53

0.00008

Table 1 presents the demographic and baseline characteristics of patients enrolled in the study and the primary outcomes comparing platelet-rich plasma (PRP) and hyaluronic acid (HA) groups. Both groups were comparable in terms of age, gender distribution, symptom duration, dominant shoulder involvement, and radiographic severity, with no statistically significant differences (p>0.70 for all). The mean age was 61.9±7.8 years in the PRP group and 62.6±8.1 years in the HA group. Males comprised 51.4% of the PRP group and 54.3% of the HA group. Baseline pain and function were also similar, with mean VAS scores of 7.4±1.0 and 7.3±1.0, and Constant scores of 42±8 and 43±9, respectively (p>0.6). For primary efficacy, PRP demonstrated a significantly greater mean reduction in VAS score from baseline to 24 weeks (−4.6±1.1) compared to HA (−3.6±1.2), with a mean difference of −1.0 (95% CI: −1.55 to −0.45; p=0.0003). Similarly, functional improvement measured by the Constant-Murley score was significantly higher in the PRP group (+30±9) versus the HA group (+21±10), with a mean difference of +9.0 (95% CI: +4.47 to +13.53; p=0.00008).

 

Table 2: Pain Trajectory (VAS, 0–10) by follow-up

Timepoint

PRP Mean (SD)

HA Mean (SD)

Effect & Test of significance (PRP−HA)

95% CI

p-value

Baseline

7.4 (1.0)

7.3 (1.0)

Mean diff = +0.10; Welch t=0.42

−0.38 to +0.58

0.676

4 weeks

5.4 (1.2)

6.0 (1.2)

Mean diff = −0.60; Welch t=−2.09

−1.17 to −0.03

0.036

12 weeks

3.8 (1.2)

4.6 (1.3)

Mean diff = −0.80; Welch t=−2.68

−1.40 to −0.21

0.007

24 weeks

2.8 (1.2)

3.7 (1.3)

Mean diff = −0.90; Welch t=−3.01

−1.50 to −0.30

0.0026

Table 2 details the mean VAS scores at different time intervals, illustrating a progressive decline in pain for both groups, with greater improvement in the PRP arm. At baseline, mean VAS scores were similar between groups (7.4±1.0 vs. 7.3±1.0; p=0.676). At 4 weeks, PRP showed a significantly larger reduction (5.4±1.2) than HA (6.0±1.2), with a mean difference of −0.60 (p=0.036). The divergence became more pronounced at 12 weeks (3.8±1.2 vs. 4.6±1.3; mean diff −0.80; p=0.007) and 24 weeks (2.8±1.2 vs. 3.7±1.3; mean diff −0.90; p=0.0026).

 

Table 3: Functional trajectory (Constant-Murley Shoulder Score, 0–100) by follow-up

Timepoint

PRP Mean (SD)

HA Mean (SD)

Effect & Test of significance (PRP−HA)

95% CI

p-value

Baseline

42 (8)

43 (9)

Mean diff = −1.00; Welch t=−0.49

−5.05 to +3.05

0.623

4 weeks

55 (9)

51 (10)

Mean diff = +4.00; Welch t=1.76

−0.53 to +8.53

0.079

12 weeks

65 (10)

58 (10)

Mean diff = +7.00; Welch t=2.93

+2.24 to +11.76

0.0034

24 weeks

72 (10)

64 (11)

Mean diff = +8.00; Welch t=3.18

+3.00 to +13.00

0.0015

Table 3 shows the progressive improvement in shoulder function across both groups as measured by the Constant-Murley Shoulder Score. At baseline, functional scores were similar (42±8 vs. 43±9; p=0.623). At 4 weeks, PRP-treated patients exhibited a modest but clinically relevant improvement (55±9 vs. 51±10), though not statistically significant (p=0.079). Significant functional gains emerged by 12 weeks, with mean scores of 65±10 for PRP and 58±10 for HA (mean diff +7.0; 95% CI: +2.24 to +11.76; p=0.0034). By 24 weeks, PRP maintained superior outcomes (72±10 vs. 64±11; mean diff +8.0; 95% CI: +3.00 to +13.00; p=0.0015).

 

Table 4: Overall clinical outcomes and safety (24 weeks, unless noted)

Outcome

PRP (n=35) n (%)

HA (n=35) n (%)

Effect & Test of significance

95% CI

p-value

VAS responders (≥2-point reduction)

30 (85.7)

22 (62.9)

RR = 1.36; χ²(1)=4.79

1.02 to 1.82

0.0287

Constant responders (≥10-point increase)

27 (77.1)

19 (54.3)

RR = 1.42; χ²(1)=4.06

1.00 to 2.02

0.0440

PGIC “much/very much improved”

24 (68.6)

17 (48.6)

RR = 1.41; χ²(1)=2.88

0.94 to 2.12

0.089

Any rescue analgesic use in weeks 1–4

10 (28.6)

15 (42.9)

RR = 0.67; χ²(1)=1.56

0.35 to 1.28

0.212

Post-injection soreness/swelling (any)

7 (20.0)

5 (14.3)

RR = 1.40; χ²(1)=0.40

0.49 to 3.99

0.526

Transient synovitis

1 (2.9)

2 (5.7)

RR = 0.50; χ²(1)=0.35

0.05 to 5.27

0.555

Infection / Serious adverse event

0 (0)

0 (0)

Any adverse event (composite)

8 (22.9)

7 (20.0)

RR = 1.14; χ²(1)=0.08

0.46 to 2.81

0.771

Table 4 summarizes comparative clinical response rates and safety outcomes between the two study groups at 24 weeks. A higher proportion of patients in the PRP group achieved clinically significant pain reduction (≥2-point VAS improvement: 85.7% vs. 62.9%; RR=1.36; p=0.0287) and functional improvement (≥10-point Constant score increase: 77.1% vs. 54.3%; RR=1.42; p=0.0440). A greater percentage of PRP-treated patients also reported being “much” or “very much improved” on the Patient Global Impression of Change scale (68.6% vs. 48.6%), though this did not reach statistical significance (p=0.089). Regarding safety, transient local soreness was observed in 20.0% of PRP and 14.3% of HA recipients, and transient synovitis in 2.9% and 5.7%, respectively—none statistically significant. No infections or serious adverse events occurred in either group, and overall adverse event rates were comparable (22.9% vs. 20.0%; p=0.771).

Discussion

The present prospective randomized study compared platelet-rich plasma (PRP) and hyaluronic acid (HA) injections in patients with degenerative shoulder arthritis and demonstrated superior pain relief and functional recovery with PRP over HA during a 24-week follow-up period. Both groups were comparable at baseline, ensuring homogeneity in age, gender, symptom duration, radiographic severity, and pre-treatment pain and function scores (Table 1). These findings align with the randomized methodology applied by Weninger V et al. (2025)[6], who also reported no significant inter-group differences at baseline in their trial comparing PRP and HA for chronic shoulder pain.

The magnitude of pain reduction (ΔVAS = −4.6 vs. −3.6) and functional gain (Δ Constant = +30 vs. +21) observed in our study parallels earlier evidence highlighting PRP’s regenerative potential. Huang SH et al. (2022)[7] emphasized the role of growth factors such as PDGF, TGF-β, and VEGF in mediating sustained analgesic and reparative effects within degenerative joint tissues, which could explain the enhanced outcomes with PRP. Gupta GK et al. (2022)[8] demonstrated that PRP provided longer-lasting symptomatic relief than HA in osteoarthritic joints due to its anti-inflammatory and chondroprotective actions.

Table 2 illustrates the pain trajectory, showing that PRP achieved statistically significant improvement as early as four weeks post-injection, with the difference widening through 12 and 24 weeks. This pattern mirrors the progressive improvement noted by Li YF et al. (2025)[9], who found PRP to yield superior outcomes at three and six months compared with saline or HA controls in shoulder tendinopathy. The present study confirms that PRP’s biologically active components likely produce both rapid and sustained modulation of intra-articular inflammation, whereas HA offers primarily biomechanical cushioning with a shorter therapeutic window.

Functional outcomes (Table 3) demonstrated a gradual yet consistently greater rise in Constant-Murley scores among PRP recipients, with statistically significant inter-group differences at 12 and 24 weeks. Comparable results were reported by Dejnek M et al. (2025)[10], who documented a mean Constant score improvement of 31 points after PRP injection compared with 22 points for HA, underscoring PRP’s superior ability to enhance muscle strength and range of motion. Dakkak M et al. (2024)[11] further noted that PRP’s regenerative influence on the glenohumeral cartilage could translate into measurable functional recovery in patients with degenerative shoulder pathology.

Table 4 summarizes the overall responder analysis, revealing that significantly more PRP-treated patients achieved clinically meaningful improvement in pain (85.7% vs. 62.9%) and function (77.1% vs. 54.3%). The proportion of patients reporting “much” or “very much improved” global impression was higher in the PRP group, though not statistically significant, possibly due to the modest sample size. Importantly, no serious adverse events were encountered, corroborating the favorable safety profile described by Ghorbani O et al. (2024)[12] in their HA trial and later reaffirmed in meta-analyses comparing PRP and HA injections in musculoskeletal disorders. The mild transient local soreness observed in a minority of PRP patients is consistent with the expected post-injection inflammatory response.

Conclusion

This prospective randomized study demonstrated that intra-articular platelet-rich plasma (PRP) injections provide superior pain relief and functional improvement compared to hyaluronic acid (HA) injections in patients with degenerative shoulder arthritis. While both treatment modalities were effective in reducing pain and improving joint function, PRP showed significantly greater and sustained improvements in Visual Analogue Scale (VAS) pain scores and Constant-Murley functional scores over a 24-week follow-up period. The results suggest that PRP, through its biological regenerative properties, offers a promising, safe, and minimally invasive alternative to conventional HA therapy for managing degenerative shoulder arthritis.

LIMITATIONS

  1. The study had a relatively small sample size (n=70), which may limit the generalizability of the findings.
  2. The follow-up duration of 24 weeks was short; longer-term outcomes and durability of PRP effects were not assessed.
  3. The study did not evaluate imaging-based cartilage or structural changes to correlate with clinical improvement.
  4. Variation in PRP preparation and platelet concentration may have introduced heterogeneity in treatment response.
  5. The absence of a placebo control group limits the ability to completely isolate treatment-specific effects.
References
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  2. El-Hakeim EH, Selim ZI, Omran EA, Hosney M, Abd-Elkader AS. Platelet rich plasma versus hyaluronic acid injection in chronic painful shoulder: Randomized blind clinical trial. Indian Journal of Rheumatology. 2022 Dec;17(4):364-70.
  3. Fossati C, Randelli FM, Sciancalepore F, Maglione D, Pasqualotto S, Ambrogi F, Menon A. Efficacy of intra-articular injection of combined platelet-rich-plasma (PRP) and hyaluronic acid (HA) in knee degenerative joint disease: a prospective, randomized, double-blind clinical trial. Archives of Orthopaedic and Trauma Surgery. 2024 Nov;144(11):5039-51.
  4. Barman A, Mishra A, Maiti R, Sahoo J, Thakur KB, Sasidharan SK. Can platelet-rich plasma injections provide better pain relief and functional outcomes in persons with common shoulder diseases: a meta-analysis of randomized controlled trials. Clinics in Shoulder and Elbow. 2021 Nov 19;25(1):73.
  5. Al Banouby M, Soliman AE, Soliman HM, Farouk HA. Comparing the Efficacy of PRP Vs Hyaluronic Acid Vs Placebo Injections in the Management of Supraspinatus Tendinopathy; Randomized Controlled Trial. International journal of health sciences.;6(S4):7834-45.
  6. Weninger V, Agócs G, Kovács N, Váncsa S, Hergár L, Baek CJ, Hegyi P, Holnapy G, Skaliczki G. Hyaluronate acid plus platelet-rich plasma is superior to steroids for pain relief less than 6 months using injection therapy of partial rotator cuff tears: A systematic review and network meta-analysis. Arthroscopy: The Journal of Arthroscopic & Related Surgery. 2025 Feb 1;41(2):304-15.
  7. Huang SH, Hsu PC, Wang KA, Chou CL, Wang JC. Comparison of single platelet-rich plasma injection with hyaluronic acid injection for partial-thickness rotator cuff tears. Journal of the Chinese Medical Association. 2022 Jun 1;85(6):723-9.
  8. Gupta GK, Shekhar S, Haque ZU, Halder S, Manjhi AK, Rai A, Gupta G, Halder Jr S, Manjhi A. Comparison of the efficacy of platelet-rich plasma (PRP) and local corticosteroid injection in periarthritis shoulder: a prospective, randomized, open, blinded end-point (PROBE) study. Cureus. 2022 Sep 17;14(9).
  9. Li YF, Xing HH, Wei CK, Chen YT, Sun YQ, Liu FL, Wu YH, Yang W. Platelet-rich plasma is more effective than hyaluronic acid injections for osteoarthritis of the knee: A meta-analysis based on randomized, double-blinded, controlled clinical trials. Arthroscopy: The Journal of Arthroscopic & Related Surgery. 2025 Jul 16.
  10. Dejnek M, Królikowska A, Kowal M, Reichert P. Comparative efficacy of platelet-rich plasma, corticosteroid, hyaluronic acid, and placebo (saline) injections in patients with lateral elbow tendinopathy: a randomized controlled trial. Journal of Clinical Medicine. 2025 Jan 13;14(2):472.
  11. Dakkak M, Saleem A, Patel D, Yeager M, Oliveira L, Gilot G, Spindler KP. A systematic review of randomized control trials looking at functional improvement of rotator cuff partial thickness tears following platelet-rich-plasma injection: a comparison of glenohumeral joint vs. subacromial bursa vs. intratendinous injection locations. JSES international. 2024 May 1;8(3):464-71.
  12. Ghorbani O, Mahdibarzi D, Yousefi-Tooddeshki P. Comparison of the short-term effect of intra-articular hyaluronic acid and platelet-rich plasma injections in knee osteoarthritis: a randomized clinical trial. Journal of Preventive Medicine and Hygiene. 2024 Aug 31;65(2): E214.
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