Experimental-based mechanobiological modeling of the anabolic and catabolic effects of breast cancer on bone remodeling

Bone is a biological tissue characterized by its hierarchical organization. This material has the ability to be continually renewed, which makes it highly adaptative to external loadings. Bone renewing is managed by a dynamic biological process called bone remodeling (BR), where continuous resorption of old bone and formation of new bone permits to change the bone composition and microstructure. Unfortunately, because of several factors, such as age, hormonal imbalance, and a variety of pathologies including cancer metastases, this process can be disturbed leading to various bone diseases. In this study, we have investigated the effect of breast cancer (BC) metastases causing osteolytic bone loss. BC has the ability to affect bone quantity in different ways in each of its primary and secondary stages. Based on a BR mathematical model, we modeled the BC cells' interaction with bone cells to assess their effect on bone volume fraction (BV/TV) evolution during the remodeling process. Some of the parameters used in our model have been determined experimentally using the enzyme-linked immune-sorbent assay (ELISA) and the MTT assay. Our numerical simulations show that primary BC plays a significant role in enhancing bone-forming cells' activity leading to a 6.22% increase in BV/TV over 1 year. On the other hand, secondary BC causes a noticeable decrease in BV/TV reaching 15.74% over 2 years.