Intraoperative Zoledronic Acid for Arthroscopic Rotator Cuff Repair: Short-Term Results From a Prospective, Randomized, Placebo-Controlled Phase II Trial

Background: Despite technical innovations and surgical improvements, retear rates after arthroscopic rotator cuff (RC) repair remain high. Preclinical studies demonstrated improved outcomes using bisphosphonates after RC repair. Purpose/Hypothesis: The purpose of this monocentric, prospective, randomized, placebo-controlled, triple-blinded phase II trial was to investigate retears in patients without osteoporosis undergoing arthroscopic RC repair with a systemic single-dose zoledronic acid. It was hypothesized that zoledronic acid would reduce retears after RC repair. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 80 patients were intraoperatively randomized to the zoledronic acid group (n = 40) or the control group (n = 40). All patients underwent magnetic resonance imaging 6 months after surgery. Range of motion, abduction strength, Constant-Murley score (CMS), American Shoulder and Elbow Surgeons (ASES) score, Subjective Shoulder Value (SSV), and Visual Analog Scale (VAS) for pain were assessed preoperatively as well as 3 and 6 months after arthroscopic RC repair. Results: At 6 months, retears were significantly lower ( P = .001) in the zoledronic acid group (n = 6; 15%) compared with the control group (n = 14; 35%). The risk of a RC retear with an additional zoledronic acid treatment (RR, 0.43 [95% CI, 0.16; 0.98]) was significantly lower compared with that of the control group (OR, 0.328; 95% CI, 0.111-0.969; P = .044). Postoperative fatty muscle infiltration of the supraspinatus was significantly lower in the zoledronic acid group compared with the control group ( P < .001). Clinical and functional outcomes significantly improved in the 2 study groups 3 and 6 months postoperatively, with better outcomes for abduction ( P = .002), forward flexion ( P = .002), external rotation ( P = .001), CMS ( P < .001), ASES score ( P < .001), SSV ( P < .001), and VAS for pain ( P < .001) in the zoledronic acid group at the final follow-up. Conclusion: An intraoperative systemic single-dose zoledronic acid reduced retears after arthroscopic RC repair. Zoledronic acid is a safe, easy-to-apply, and cost-effective augmentation technique for patients undergoing arthroscopic RC repair. Registration: NCT05677152 (ClinicalTrials.gov identifier).