Effect of denosumab on low bone mineral density in postmenopausal Japanese women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: 24-month results

Breast Cancer. 2019 Jan;26(1):106-112. doi: 10.1007/s12282-018-0896-y. Epub 2018 Jul 27.

Abstract

Background: Aromatase inhibitors (AI) have been established as the gold-standard therapy for postmenopausal patients. Worldwide, adjuvant denosumab at a dose of 60 mg twice per year reduces the risk of clinical fractures in postmenopausal patients with breast cancer who received AI. However, the efficacy of denosumab in the treatment of AI-associated bone loss had not been prospectively evaluated in Japan. Previously, we reported the 12-month effect of denosumab in Japanese patients for the first time; the primary endpoint was the change in the percentage of bone mineral density (BMD) of the lumbar spine from baseline to 12 months.

Methods: This secondary follow-up study prospectively evaluated the change in the percentage of BMD of the lumbar spine from baseline to 24 months. Postmenopausal women with early-stage, histologically confirmed, hormone receptor-positive, invasive breast cancer who were receiving or scheduled to receive AI were included. Denosumab was administered subcutaneously on day 1 of the study and then 6, 12, 18, and 24 months. The lumbar spine and bilateral femoral neck BMD was measured at baseline and 6, 12, 18, and 24 months.

Results: At 18 and 24 months, the lumbar spine BMD increased by 5.9 and 7.0%, respectively. The femoral neck BMD also increased. Grade ≥ 2 hypocalcemia, osteonecrosis of the jaw, and atypical femoral fractures did not occur.

Conclusions: Our prospective study showed that semiannual treatment with denosumab was associated with continuously increased BMD in Japanese women receiving adjuvant AI therapy for up to 24 months, regardless of prior AI treatment.

Keywords: Aromatase inhibitor; Bone mineral density; Breast cancer; Denosumab.

Publication types

  • Clinical Trial

MeSH terms

  • Absorptiometry, Photon
  • Aged
  • Antineoplastic Agents, Hormonal / adverse effects*
  • Aromatase Inhibitors / adverse effects*
  • Bone Density / drug effects
  • Bone Density Conservation Agents / pharmacology*
  • Bone Density Conservation Agents / therapeutic use
  • Bone Resorption / chemically induced
  • Bone Resorption / diagnostic imaging
  • Bone Resorption / drug therapy*
  • Breast Neoplasms / therapy*
  • Chemotherapy, Adjuvant / adverse effects
  • Chemotherapy, Adjuvant / methods
  • Denosumab / pharmacology*
  • Denosumab / therapeutic use
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Injections, Subcutaneous
  • Japan
  • Lumbar Vertebrae / diagnostic imaging
  • Middle Aged
  • Postmenopause
  • Prospective Studies
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Bone Density Conservation Agents
  • Denosumab