Bone resorption and bone metastasis risk

Publication date: September 2018
Source:Medical Hypotheses, Volume 118
Author(s): Katlynn M. Mathis, Kathleen M. Sturgeon, Renate M. Winkels, Joachim Wiskemann, Mary Jane De Souza, Katherine H. Schmitz
Breast cancer tumors have a tendency to metastasize to the bone. After development of a bone metastasis, the median survival time is 40 months. Currently, little is known about the modifiable risk factors for developing bone metastases in women diagnosed with breast cancer. One possible modifiable risk factor is increased bone resorption. Increased bone resorption is caused by an imbalance between osteoblasts and osteoclasts favoring osteoclast-driven bone resorption. Osteoclast activity results in the release of growth factors from the bony matrix that are requirement for successful breast cancer tumor cell proliferation within the bone. Mice studies have shown that mice that have been genetically engineered to have higher bone mineral density, and thus lower bone resorption, have a decreased incidence of bone metastases. Alternatively, mice genetically engineered to have lower bone mineral density or increased bone resorption have a higher incidence of bone metastases. In human studies, antiosteoporotic drugs have been shown to decrease osteoclast activity and prevent bone metastases. These studies suggest that increased osteoclast activity, which results in low bone mineral density, may be a modifiable risk factor for developing bone metastases in women with breast cancer. Women undergoing chemotherapy for breast cancer develop low bone mineral density in response to the direct effects of chemotherapeutic drugs on bone cells—including osteoclasts, osteoblasts, and osteocytes—and through the decrease in circulating estrogen as a result of chemotherapy-induced ovarian dysfunction. Therefore, it is important for future studies to determine the risk of developing bone metastases associated with increasing bone resorption as measured by low or decreasing bone mineral density in women diagnosed with breast cancer, as well as to determine the best intervention(s) to promote a balance between osteoclasts and osteoblasts to favor osteoblast activity during chemotherapy treatment.



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