Denosumab Delays Bone Complications in Women with Metastatic Breast Cancer

Among women with bone metastases from breast cancer, denosumab may be more effective than Zometa® (zoledronic acid) at delaying or preventing bone complications such as fracture. The results of this Phase III clinical trial were published in the Journal of Clinical Oncology.

Metastatic cancer refers to cancer that has spread to distant sites in the body. Several types of cancer—including breast cancer—have a tendency to spread to the bone. Bone metastases can lead to serious problems such as fracture and spinal cord compression and may require treatment with surgery or radiation therapy.

Bisphosphonate drugs such as Zometa are commonly used to reduce the risk of complications from bone metastases. Researchers continue, however, to explore new approaches to treatment.

Denosumab is a drug that targets a protein known as the RANK ligand. This protein regulates the activity of osteoclasts (cells that break down bone). Denosumab has been approved for the treatment of postmenopausal osteoporosis and has also shown promising results in the management of bone metastases and treatment-related bone loss.

To directly compare denosumab to Zometa among breast cancer patients with bone metastases, researchers conducted a Phase III clinical trial among more than 2,000 patients. Study participants were assigned to receive either denosumab or Zometa.

The objective of the study was to determine whether the occurrence of bone complications (“skeletal related events”) differed between the two study groups. The bone complications that were evaluated were fracture, radiation to the bone, surgery to the bone, and spinal cord compression.

  • Patients treated with denosumab remained free of bone complications longer than patients treated with Zometa.
  • Overall survival and time to cancer progression were similar among patients treated with Zometa and patients treated with denosumab.
  • Osteonecrosis of the jaw (an uncommon but serious side effect) was seen infrequently in both study groups (2% of patients treated with denosumab and 1.4% of patients treated with Zometa).

The results of this study suggest that denosumab may be more effective than Zometa at delaying or preventing skeletal complications in breast cancer patients with bone metastases.


Stopeck AT, Lipton A, Body J-J et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. Journal of Clinical Oncology [early online publication]. November 8, 2010.