Predicting the risk of fractures in metastatic bones
Bone metastases are associated with multiple and severe complications, including fractures. New anticancer targeted therapies and immunotherapy have considerably increased life expectancy, even for patients whose cancers have spread to distant parts of the body; however, bone metastases disrupt bone remodelling, which increases fracture risk. To estimate the fracture risk in patients, fragility scores are used that rely on qualitative evaluation from quantitative computed tomography scans. However, this approach lacks sensitivity and specificity. The development of patient-specific finite element models is an alternative approach for measuring metastatic bone strength. These models are based on clinical images and are used to provide a detailed distribution of stress and strain in the metastatic bone. Again, the limited knowledge of metastatic bone mechanical properties limits their widespread implementation.
Predicting fracture risk
Undertaken with the support of the Marie Skłodowska-Curie Actions (MSCA) programme, the METABONE project developed a novel methodology to better predict the fracture risk of metastatic femurs. The working hypothesis was that the strength of the metastatic bone depends on the characteristics of both the bone and the cancer lesion, as well as the applied forces. Moreover, fractures in metastatic bones usually occur spontaneously during daily life activities, clearly indicating that the simulation should also consider different loading conditions. “We developed a dedicated experimental protocol to characterise the mechanical properties of the metastatic bone tissue in human patients,” explains the MSCA research fellow Aurélie Levillain. METABONE followed the paradigm of osteoporosis in fracture prediction using numerical simulation and finite element analysis. A subject-specific finite element of the metastatic femur was developed to predict its failure load. Moreover, a sensitivity study was conducted to evaluate the influence of tumour mechanical properties on the predicted failure load, depending on the size and location of the metastasis.
Characterisation of tumour mechanical properties
The METABONE methodology can also be employed to provide insight into the biophysical characteristics of primary tumours as well as of normal bone tissue. Using this strategy, researchers observed that the mechanical properties of tumours depended on the organ/tissue of origin. “We discovered that changes in composition between normal and bone metastatic areas depend on the type of lesion and the origin of the primary cancer,” highlights Levillain.
A new clinical oncology tool?
The METABONE approach is intended to provide clinicians with a personalised decision tool to predict the risk of fracture, considering the geometry and strength of the femur. It offers the possibility of changing parameters such as the mechanical properties and the size of the metastases for patient follow-up. This will enable clinicians to predict fracture risk evolution as disease progresses. It may also be used to assess the efficacy of treatment on the size of metastases and fracture risk. The METABONE team is currently validating the model on ex vivo femurs. The next step is to bring the tool to the clinic to predict the fracture risk of patients with bone metastases and improve their quality of life.
Keywords
METABONE, fracture risk, femur, bone metastases, finite element models, fracture prediction
