Bone turnover markers: tools for prognosis and monitoring response to bisphosphonates?

Skeletal homeostasis is maintained by spatially coupled and balanced processes of osteolysis and osteogenesis. Several factors across the breast cancer continuum (e.g., adjuvant therapies, bone metastases in advanced disease) can disrupt this balance. Circulating levels of specific biochemical markers released during bone turnover provide relatively non-invasive means to assess ongoing rates of skeletal metabolism. Such markers may provide insight into the risk of bone loss and fractures in women with osteoporosis and during adjuvant therapy for breast cancer. In addition, bone marker levels and alterations might reflect tumor-bone interactions and response to bisphosphonate treatment in patients with bone metastases. Thus far, the largest body of evidence supports a potential role for urinary N-terminal cross-linked telopeptide of type I collagen (NTX) in predicting risks of skeletal morbidity and death, and monitoring response during zoledronic acid treatment, in patients with bone metastases. Other possible applications for bone markers include diagnosis of bone metastases and monitoring bone disease progression. Ongoing clinical trials evaluating the potential for bone marker changes to provide insights into the disease course and response to various classes of antiresorptive therapies are expected to expand the role of bone markers in the management of patients with breast cancer.