Aromatase Inhibitor-Associated Musculoskeletal Syndrome: Understanding Mechanisms and Management

Front Endocrinol (Lausanne). 2021 Jul 27:12:713700. doi: 10.3389/fendo.2021.713700. eCollection 2021.


Aromatase inhibitors (AIs) are a key component in the chemoprevention and treatment of hormone receptor-positive (HR+) breast cancer. While the addition of AI therapy has improved cancer-related outcomes in the management of HR+ breast cancer, AIs are associated with musculoskeletal adverse effects known as the aromatase inhibitor-associated musculoskeletal syndrome (AIMSS) that limit its tolerability and use. AIMSS is mainly comprised of AI-associated bone loss and arthralgias that affect up to half of women on AI therapy and detrimentally impact patient quality of life and treatment adherence. The pathophysiology of AIMSS is not fully understood though has been proposed to be related to estrogen deprivation within the musculoskeletal and nervous systems. This review aims to characterize the prevalence, risk factors, and clinical features of AIMSS, and explore the syndrome's underlying mechanisms and management strategies.

Keywords: aromatase inhibitor; aromatase inhibitor-associated musculoskeletal syndrome; aromatase inhibitor-induced arthralgia; aromatase inhibitor-induced bone loss; breast cancer.

Publication types

  • Review

MeSH terms

  • Aromatase Inhibitors / adverse effects*
  • Aromatase Inhibitors / therapeutic use
  • Arthralgia / chemically induced
  • Body Mass Index
  • Bone Density / drug effects
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / prevention & control
  • Chemoprevention
  • Female
  • Humans
  • Musculoskeletal Diseases / chemically induced*
  • Musculoskeletal Diseases / epidemiology
  • Musculoskeletal Diseases / therapy
  • Receptors, Estrogen / analysis
  • Risk Factors


  • Aromatase Inhibitors
  • Receptors, Estrogen