Treatment Modalities for Aromatase Inhibitor-Associated Musculoskeletal Syndrome (AIMSS): A Scoping Review of Prospective Treatment Studies

Justin Andrew Bobo,1 Barbara Lubrano,2 Raul Rosario-Concepcion,3 Alejandra Cuartas-Abril,2 Pooja Advani,4 Saranya Chumsri,4,5 Barbara K Bruce2 1Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA; 2Department of Psychiatry & Psychology, Mayo Clinic, Jacksonville, FL, USA; 3Miami Neuroscience Institute, Baptist Health, Miami, FL, USA; 4Department of Medical Oncology, Mayo Clinic, Jacksonville, FL, USA; 5Department of Medicine, Mayo Clinic, Jacksonville, FL, USACorrespondence: Barbara K Bruce, Department of Psychiatry and Psychology, Mayo Clinic, Florida, 4315 Pablo Oaks Court, Jacksonville, FL, 32224, USA, Tel +1 (904) 953-7286, Fax +1 (904) 953-0461, Email [email protected]: Aromatase inhibitors (AI’s) are effective adjuvant treatments for postmenopausal patients with hormone receptor-positive breast cancer. However, AIs are often associated with diffuse joint and muscle pain, referred to as aromatase inhibitor-associated musculoskeletal syndrome (AIMSS), the symptoms of which are associated with negative impacts and reduced adherence to AI therapy. As more interventions for AIMSS continue to be investigated, a scoping review is needed to survey and summarize the types of interventions and outcomes assessed in studies conducted to date, which may help identify areas needing attention or additional focus in future research. Online databases were searched (from inception to January 8, 2025) to identify 74 reports from prospective studies of interventions for AIMSS pain, stiffness, or interference with functioning. Such interventions were classified as pharmacological (14 reports), complementary/alternative (43 reports), or rehabilitative (17 reports). Included papers required the presence of AIMSS symptoms at enrollment. Several interventions were deemed promising for reducing AIMSS symptoms based on positive results from individual reports, including duloxetine (3 reports from 2 studies), vitamin B12 (2 reports), vitamin D (2 reports), calcitonin (1 report), prednisolone (1 report), glucosamine and chondroitin (1 report), various mind-body (14 reports from 12 studies) and traditional medicine interventions (3 reports), and switching to another AI (1 report). Many positive findings were from uncontrolled studies or were from single studies that await replication in independent cohorts, and no studies focused on structured psychological interventions. The durations for all reviewed studies were brief relative to the expected 5– 10-year course of AI therapy. Intervention effects on a wide range of outcomes were studied, including pain or stiffness (70 reports), functioning/disability (34 reports), quality of life (37 reports), mental health symptoms (25 reports), pain self-efficacy (4 reports), and AI persistence (3 reports). However, intervention effects on other important endpoints such as cancer recurrence, survival, healthcare utilization/costs, and caregiver experiences are unclear. The knowledge gaps and limitations identified in this scoping review constitute areas in urgent need of further research and attention.Keywords: aromatase inhibitor-associated musculoskeletal syndrome, AIMSS, aromatase inhibitors, breast cancer, pain management, musculoskeletal symptoms