February 5, 2009

Denosumab: A New Treatment to Improve Bone Density in Women Treated with an Aromatase Inhibitor

By Lee S. Schwartzberg, MD, FACP

Although several studies have shown that aromatase inhibitors reduce the risk of breast cancer recurrence among postmenopausal breast cancer patients, aromatase inhibitors have been linked with bone loss. Use of drugs that reduce bone loss may therefore benefit women who are treated with an aromatase inhibitor.

Denosumab is an experimental drug that is given as a twice yearly subcutaneous injection. Denosumab may preserve bone density in select groups of breast cancer patients undergoing treatment with an aromatase inhibitor.

Below, Lee S. Schwartzberg, MD, FACP, comments on presentations made at the 2007 San Antonio Breast Cancer Symposium regarding the monoclonal antibody denosumab and bone density among women treated with an aromatase inhibitor.

One of the most interesting presentations at The San Antonio Breast Cancer Symposia was a late-breaking abstract on the use of denosumab, a new monoclonal antibody, in clinical trial as an alternative treatment for the preservation of bone density in selected groups of patients.1 Denosumab is a novel agent that inhibits bone resorption through its effect on the RANK ligand, an important and central pathway in the development of bone. This study looked at denosumab in women with non-metastatic breast cancer receiving AI [aromatase inhibitor] therapy. The women had some degree of osteopenia, defined as a T-score [comparison of a patient's BMD to that of a healthy thirty-year-old of the same sex and ethnicity] of less than -1 but greater than -2.5. They were excluded if they had osteoporosis or had previously used oral bisphosphonates [agents that may prevent bone loss]. It was a placebo-controlled study. The drug was delivered subcutaneously ever six months. Compared to placebo, there was a 5.5% difference in lumbar spine bone mineral density at 12 months after initiation of denosumab, which increased to 7.6% difference at 24 months; this was highly statistically significant. Similar results were seen in the analysis of the total hip bone density and distal third of the radial bone [forearm] density. Analysis of adverse events showed minimal toxicity attributable to denosumab. The degree of joint pain in the extremities, back pain, and fatigue were virtually identical in both arms. The conclusion was that denosumab, a new monoclonal antibody with a novel mechanism of action, provided consistent increases in bone mineral density over the duration of the 24 month study, and was very well tolerated. There are ongoing clinical trials with denosumab [in metastatic breast cancer] as well.


1 Ellis G, Bone HG, Chlebowski R et al. A phase 3 study of the effect of denosumab therapy on bone mineral density in women receiving aromatase inhibitors for non metastatic breast cancer. Presented at the 30th Annual San Antonio Breast Cancer Symposium. San Antonio, TX, December 13-16, 2007. Abstract 47.

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