Patient Population:

15 randomized-controlled trial (RCT) studies were included in the review; nine from Europe and six from the Americas. 1023 patients with a diagnosis of glenohumeral osteoarthritis (OA) (Male = 498, Female = 575) with an average age of 65.3 were included in this meta-analysis.  

Intervention:

Various hyaluronic acid (HA) infiltrations were used as therapeutic interventions. Five studies used various injections of 2mL of 8mg/mL Hylan G-F 20. Other studies used Durolane® (nonanimal hyaluronic acid; NASHA), 40mg/2mL injection of sodium hyaluronate (OstenilPlus), HYADD®4-G (Hymovis®-, Fidia Farmaceutici SpA), high molecular weight hyaluronate (2.5 mL each) Euflexxa® (1% sodium hyaluronate), and HA of lower molecular weight. Three studies also combined viscosupplemented injections (Hyalgan 20 mg/2 mL,  Hyalubrix [30 mg/2 mL], and ​​HMW HA [HyalOne® 60 mg/4 mL]) with physical therapy (PT).  

Comparison:

No intervention, PT, corticosteroid injection, or platelet-rich plasma (PRP) injection (n=397). 

• Seven studies had no control group.  

• Three studies had PT as comparison groups.  

• Two studies had corticosteroid injection (three 40mg/mL methylprednisolone acetate injections, and a single triamcinolone hexacetonide injection) comparison groups.  

• Two studies had placebo (three weekly phosphate-buffered saline injections, and no treatment) control groups.  

• One study had a PRP injection (single 6mL Leukocyte-PRP) comparison group. 

Outcome:

The meta-analysis adopted a random-effects model for statistical analysis. 

• Intra-articular application of HA significantly improved pain and function compared to baseline in participants with shoulder-OA. Therefore, HA may be an effective pain-relieving intervention for shoulder-OA.  

• HA injection combined with PT showed superior scores compared to PT alone, with an overall effect size (ES) of 4.43 (95% CI= 1.89-6.97, p = 0.00006), demonstrating improved pain and function (measured by Constant scores and range of motion [ROM]).  

• Pooled analysis of VAS showed a significant improvement in the ES of the HA injections compared to corticosteroid injections (−1.47; 95% CI = −2.39 to −0.55, p = 0.002). 

• The singular study (Kirschner et al.) contrasting HA to PRP intervention groups used the Shoulder Pain and Disability Index (SPADI), American Shoulder and Elbow Surgeons (ASES) score, current/average numerical rating scale (NRS) pain scores, satisfaction, and side effects as outcome measures. Their results demonstrated similar improvement in pain and function between the two groups, necessitating further inquiry into which approach is superior.  

• Pooled analysis of VAS showed nonsignificant improvement in pain when comparing ES of HA intervention groups to no treatment and placebo injection groups (−2.30; 95% CI = −6.37 to 1.76, p = 0.27), meaning there is a strong possibility for placebo effect related to the application of HA.