Chemotherapy and adjuvant therapies' impact on the internal remodeling process of bone and its mechanical behavior for breast cancer patients.

Breast cancer is a significant public health issue affecting women worldwide. While advancements in treatment options have led to improved survival rates, the impact of breast cancer and its treatments on bone health cannot be overlooked. Bone remodeling is a complex process regulated by the delicate balance between bone formation and resorption. Any disruption to this balance can lead to decreased bone density, increased fracture risk, and compromised physical function. To investigate the effects of breast cancer and its treatments on bone remodeling, a finite element model was developed in this study. This model incorporated bone remodeling equations to simulate the mechanical behavior of bone under different conditions. The ABAQUS/UMAT software was used to simulate the behavior of bone tissue under the influence of breast cancer and treatments. Our findings suggest that bone loss is more pronounced after secondary breast cancer and treatment, leading to bone loss (6%-19% decrease in BV/TV), reduced bone stimulation, and decreased effectiveness of physical activity on recovery. These results highlight the importance of early intervention and management of bone health in breast cancer patients to mitigate the negative impact of cancer and treatment on bone remodeling.

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.

Toward a Mathematical Modeling of Diseases' Impact on Bone Remodeling: Technical Review.

A wide variety of bone diseases have hitherto been discovered, such as osteoporosis, Paget's disease, osteopetrosis, and metastatic bone disease, which are not well defined in terms of changes in biochemical and mechanobiological regulatory factors. Some of these diseases are secondary to other pathologies, including cancer, or to some clinical treatments. To better understand bone behavior and prevent its deterioration, bone biomechanics have been the subject of mathematical modeling that exponentially increased over the last years. These models are becoming increasingly complex. The current paper provides a timely and critical analysis of previously developed bone remodeling mathematical models, particularly those addressing bone diseases. Besides, mechanistic pharmacokinetic/pharmacodynamic (PK/PD) models, which englobe bone disease and its treatment's effect on bone health. Therefore, the review starts by presenting bone remodeling cycle and mathematical models describing this process, followed by introducing some bone diseases and discussing models of pathological mechanisms affecting bone, and concludes with exhibiting the available bone treatment procedures considered in the PK/PD models.