Modeling and simulation of bone cells dynamic behavior under the late effect of breast cancer treatments.

Breast Cancer (BC) treatments have been proven to interfere with the health of bones. Chemotherapy and endocrinal treatment regimens such as tamoxifen and aromatase inhibitors are frequently prescribed for women with BC. However, these drugs increase bone resorption and reduce the Bone Mineral Density (BMD), thus increasing the risk of bone fracture. In the current study, a mechanobiological bone remodeling model has been developed by coupling cellular activities, mechanical stimuli, and the effect of breast cancer treatments (chemotherapy, tamoxifen, and aromatase inhibitors). This model algorithm has been programmed and implemented on MATLAB software to simulate different treatment scenarios and their effects on bone remodeling and also predict the evolution of Bone Volume fraction (BV/TV) and the associated Bone Density Loss (BDL) over a period of time. The simulation results, achieved from different combinations of Breast Cancer treatments, allow the researchers to predict the intensity of each combination treatment on BV/TV and BMD. The combination of chemotherapy, tamoxifen, and aromatase inhibitors, followed by the combination of chemotherapy and tamoxifen remain the most harmful regimen. This is because they have a strong ability to induce the bone degradation which is represented by a decrease of 13.55% and 11.55% of the BV/TV value, respectively. These results were compared with the experimental studies and clinical observations which showed good agreement. The proposed model can be used by clinicians and physicians to choose the most appropriate combination of treatments, according to the patient's case.

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.