Skeletal complications of breast cancer therapies

Abstract

Nonsurgical treatment options, such as hormonal therapy, chemotherapy, radiation, and bisphosphonate therapy, are undoubtedly improving outcomes for women with breast cancer; however, these therapies also carry significant skeletal side effects. For example, adjuvant hormonal treatments, such as aromatase inhibitors that disrupt the estrogen-skeleton axis, have the potential to cause decreased bone mineral density. Similarly, chemotherapy often induces primary ovarian failure in premenopausal women, resulting in decreased levels of circulating estrogen and subsequent osteopenia. In both cases, women receiving these therapies are at an increased risk for the development of osteoporosis and skeletal fracture. Furthermore, women undergoing radiation therapy to the upper body may have an increased incidence of rib fracture, and those receiving bisphosphonates may be vulnerable to the development of osteonecrosis of the jaw. Therefore, women with breast cancer who are undergoing any of these therapies should be closely monitored for bone mineral loss and advised of skeletal health maintenance strategies.

Fig. 1

Contribution of estrogens and androgens to bone remodeling. Estrogen and androgens help to maintain a balance between bone formation and bone resorption. Estrogen inhibits osteoclast activity and contributes to osteoclast apoptosis; androgens are converted to estrogen by aromatization and may also directly affect osteoblast differentiation. As such, a decrease in estrogen and/or androgens leads to increased bone resorption and an imbalance in bone remodeling, which ultimately manifests as bone loss (–3, 73, 74). Adapted from Skeletal Complications Across the Cancer Continuum CME Lecture 2005 series with permission from the Postgraduate Institute for Medicine.

Fig. 2

Extent of bone loss due to cancer therapy. Menopausal women lose bone at a rate of1% to 2% yearly. Cancer treatments, such as aromatase inhibitor therapy and chemotherapy, accelerate this process, leading to significant bone loss and subsequent skeletal complications (, –79). Adapted from Skeletal Complications Across the Cancer Continuum CME Lecture 2005 series with permission from the Postgraduate Institute for Medicine.