Bone Health During Adjuvant Aromatase Inhibitor Therapy in Non-Metastatic Hormone Receptor-Positive Breast Cancer: from Pathophysiology to Evidence-Based Prevention and Management

Abstract

Introduction: Aromatase inhibitors (AIs) are the cornerstone of adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive early breast cancer. Although these agents substantially reduce recurrence, profound estrogen deprivation accelerates bone remodeling, leading to bone mineral density (BMD) loss and increased fracture risk. Objective: This review critically summarizes current understanding of AI-induced bone loss, integrating evidence on epidemiology, pathophysiology, fracture risk assessment, preventive strategies, pharmacological interventions, and clinical guidelines.

Methods: A comprehensive literature review was performed using PubMed/MEDLINE, Scopus, and Google Scholar, prioritizing randomized controlled trials, meta-analyses, systematic reviews, and contemporary guidelines.

Results: AI therapy induces accelerated bone loss exceeding physiological postmenopausal depletion, predominantly affecting trabecular-rich sites. While dual-energy X-ray absorptiometry remains the standard for monitoring BMD, complementary tools including trabecular bone score, FRAX, and bone turnover biomarkers improve identification of high-risk patients. Randomized trials demonstrate that bisphosphonates and denosumab effectively prevent AI-associated bone loss, with selected agents providing additional reductions in recurrence. Lifestyle modification, calcium and vitamin D optimization, and individualized risk stratification remain essential components of multidisciplinary management.

Conclusions: Bone health preservation should be considered fundamental to adjuvant endocrine therapy. Contemporary management requires individualized fracture risk assessment, early identification of high-risk patients, evidence-based implementation of interventions, and multidisciplinary collaboration.