Single versus triple low-molecular-weight hyaluronic acid injection strategies with shockwave therapy for rotator cuff lesions: A randomized study with an exploratory historical comparator

Abstract

Background Rotator cuff lesions without full-thickness tear commonly cause shoulder pain and functional limitation. Hyaluronic acid (HA) injections and extracorporeal shockwave therapy (ESWT) are widely used conservative treatments, but the optimal HA dosing strategy combined with ESWT remains unclear. Objective To evaluate the additional clinical benefit of ESWT combined with a single LMWHA injection and to explore whether reducing LMWHA injections from three to one is associated with differences in longer-term outcomes. Methods In the prospective randomized arm, participants received a single LMWHA injection with real (n = 28) or sham ESWT (n = 29). A prespecified historical cohort receiving three weekly LMWHA injections plus ESWT (n = 31) was included for exploratory comparison. CMS at 12 months was the principal efficacy outcome. Results Among 57 randomized participants and 31 in the exploratory historical cohort, 1LMWHA + 1ESWT produced better 12-month CMS than 1LMWHA (88.1 ± 7.6 vs 79.0 ± 14.0; adjusted mean difference, 9.55 points; 95% CI, 4.14 to 14.97). CMS PASS was achieved by 84.6% versus 55.6% of participants (p = 0.035). The exploratory three- versus single-injection ESWT comparison showed a smaller 12-month CMS difference (adjusted, −1.63 points; 95% CI, −7.04 to 3.79). MRI progression occurred only in the 1LMWHA group (3/27 vs 0/55) and was analyzed descriptively. Conclusion A single LMWHA injection combined with ESWT improved 12-month functional outcomes compared with sham ESWT. No significant differences were detected after 6 months relative to the exploratory historical three-injection regimen, but equivalence or non-inferiority cannot be inferred.