Antiosteoporotic treatment promotes tendon-to-bone healing after rotator cuff repair

Aims: To determine whether antiosteoporosis treatment promotes tendon-to-bone healing after rotator cuff repair (RCR) in animal models. Methods: This systematic review adhered to the PRISMA guidelines and was registered on PROSPERO (registration number: CRD42024519176). PubMed, Web of Science, Embase, and the Cochrane Library databases were searched from the inception to 13 January 2025. All the studies that used antiosteoporotic treatment as an intervention after RCR in animal models were included. The methodological quality was assessed using SYRCLE's risk of bias tools. The following data were extracted: author's name, animal characteristics, injury model, intervention measures, and main outcomes. Two reviewers independently conducted the literature search, data extraction, and quality assessment. Results: A total of 19 studies were included. Bisphosphonates (n = 5), parathyroid hormone (PTH) (n = 8), growth factors (n = 3), raloxifene (n = 1), denosumab (n = 1), and sclerostin antibody (n = 1) were applied as interventions. Overall, 15 studies used an animal model of rats, along with two in rabbits and two in sheep. Histology, imaging, biomechanics, muscle quality, gene expression, and serum biochemistry were evaluated as outcomes. Out of 16 studies that evaluated histological outcomes, 12 reported that antiosteoporosis treatment significantly promoted histological healing at the repair site. All ten studies which assessed bone microstructure showed that this was significantly improved. Of the 15 animal studies, 13 indicated that the biomechanical properties were enhanced following RCR when using antiosteoporotic treatment. All three studies reported that muscle quality was significantly improved, and all five studies found that the gene expression and serum biochemistry associated with osteogenesis were significantly elevated. Conclusion: The current study had high heterogeneity and major methodological flaws in the included studies, which limit the scope of these conclusions. However, based on histological, radiological, biomechanical, muscle quality, and serum biochemical analyses, antiosteoporosis treatments may be considered to enhance tendon-to-bone healing after RCR.