Management of aromatase inhibitor-associated bone loss in postmenopausal women with breast cancer: practical guidance for prevention and treatment

• Published in: Annals of oncology Vol. 22; no. 12; pp. 2546 - 2555
• Main Authors: Hadji, P., Aapro, M.S., Body, J.J., Bundred, N.J., Brufsky, A., Coleman, R.E., Gnant, M., Guise, T., Lipton, A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-12-2011; Oxford University Press
• Subjects: Antineoplastic agents; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; aromatase inhibitor; Aromatase Inhibitors - adverse effects; Aromatase Inhibitors - therapeutic use; Biological and medical sciences; bisphosphonate; Bone Density Conservation Agents - therapeutic use; bone loss; breast cancer; Breast Neoplasms - drug therapy; Diphosphonates - therapeutic use; Diseases of the osteoarticular system; Female; fracture risk; Gynecology. Andrology. Obstetrics; Humans; Imidazoles; Mammary gland diseases; Medical sciences; Osteoporosis, Postmenopausal - chemically induced; Osteoporosis, Postmenopausal - prevention & control; Osteoporosis. Osteomalacia. Paget disease; Pharmacology. Drug treatments; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Risk Factors; Tumors; Zoledronic Acid; bisphosphonate; breast cancer; zoledronic acid; bone loss; aromatase inhibitor; fracture risk; Antineoplastic agent; Antiosteoporotic; Breast disease; Menopause; Diseases of the osteoarticular system; Antiresorptive agent; Diphosphonic acid derivatives; Fracture; Bisphosphonates; Prevention; Zoledronic acid; Postmenopause; Adult; Female; Bone defect; Woman; Osteopenia; Human; Aromatase inhibitor; Breast cancer; Malignant tumor; Management; Trauma; Guidance; Mammary gland diseases; Clinical management; Treatment; Risk factor; Cancer
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdr017

Bone mineral density (BMD)-based guidelines for bone-directed therapy in women with early breast cancer (EBC) appear inadequate for averting fractures, particularly during aromatase inhibitor (AI) therapy. Therefore, an algorithm was developed to better assess risk and direct treatment (Hadji P, Body JJ, Aapro MS et al. Practical guidance for the management of aromatase inhibitor-associated bone loss. Ann Oncol 2008; 19: 1407–1416). Here, we provide updated guidance on pharmacologic interventions to prevent/treat aromatase inhibitor-associated bone loss (AIBL).
Systematic literature review identified recent advances in preventing/treating AIBL. Individual agents were assessed based on trial size, design, follow-up, and safety.
Fracture risk factors in patients with EBC remain unchanged (Hadji P, Body JJ, Aapro MS et al. Practical guidance for the management of aromatase inhibitor-associated bone loss. Ann Oncol 2008; 19: 1407–1416). The World Health Organization Fracture Risk Assessment Tool algorithm includes fracture risk factors plus BMD but does not adequately address AIBL effects. Several antiresorptives can prevent/treat AIBL. However, concerns regarding compliance and long-term efficacy/safety remain. Overall, evidence is strongest for twice-yearly zoledronic acid (ZOL), and recent advances support additional anticancer benefits from ZOL.
All patients initiating AIs need advice regarding exercise, calcium/vitamin D supplements, baseline BMD monitoring (when available), and bone-directed therapy if T-score <-2.0 or at least two fracture risk factors were observed. Patients with T-score > -2.0 and no risk factors should be managed based on BMD loss during years 1–2. Unsatisfactory compliance/decreasing BMD after 12–24 months on oral bisphosphonates should trigger a switch to i.v. bisphosphonate.