Predicting mechanoregulatory responses in bone during breast cancer metastasis: A Finite Element Analysis

Breast cancer metastasises to bone in 70–80% of patients with advanced disease. Bone cells contribute to tumour metastasis by activating bone resorption, which releases biochemical factors that stimulate tumour cell proliferation. The local mechanical environment of bone tissue is altered during early metastasis, prior to the formation of overt osteolytic metastasis. According to mechanoregulation theory, these changes might activate mechanobiological responses in bone cells and thereby contribute to osteolytic resorption. However, whether mechanobiological responses of bone cells drive osteolysis during metastasis is unknown. The objective of this study was to apply a computational mechanoregulation framework to predict how early changes in the bone mechanical environment contribute to osteolysis. Subject-specific finite element (FE) models were developed to predict the mechanical environment within bone tissue during early stage metastasis (3 weeks post-inoculation). We then applied a mechanoregulation algorithm to predict changes in bone tissue density as a function of the evolving mechanical environment due to tumour invasion. Substantial bone loss was predicted in the greater trochanter region, which coincides with experimental reports of regional bone loss in this animal model. Moreover, application of the mechanoregulation algorithm predicted that the mechanical environment evolved in a similar manner to that predicted through subject-specific finite element (FE) models. This is the first study to implement a computational mechanoregulation framework to predict the development of osteolysis. Our findings support the hypothesis that early changes in the physical environment of bone tissue during metastasis may elicit mechanobiological cues for bone cells and activate osteolytic destruction.