Aromatase inhibitor–associated musculoskeletal pain: An overview of pathophysiology and treatment modalities

Since their introduction into clinical use in the 1970s, aromatase inhibitors have been a cornerstone of therapy for estrogen-receptor positive breast cancer in postmenopausal women. Unfortunately, this therapy leads to estrogen depletion in the body, which can lead to unpleasant side effects such as menopausal symptoms like hot flashes, insomnia, slightly increased risk of ischemic heart disease, accelerated bone loss leading to higher osteoporosis risk, and most significantly, arthralgias. The joint pain induced by aromatase inhibitor therapy is frequently cited as the leading cause of premature discontinuation; approximately 50% of patients will report new onset or worsening joint pain 1 year after therapy initiation, approximately 30% of patients discontinue therapy after 1 year, and only 50%–68% of patients remain fully compliant with therapy after 3 years. This article will describe risk factors for aromatase inhibitor–associated musculoskeletal syndrome, including genetic predispositions correlated with an increased risk of this syndrome, explain the currently understood pathophysiology, and give an overview of effective treatment options in managing this syndrome.