Fracture risk assessment and clinical decision making for patients with metastatic bone disease

Abstract

Metastatic breast, prostate, lung, and other cancers often affect bone, causing pain, increasing fracture risk, and decreasing function. Management of metastatic bone disease (MBD) is clinically challenging when there is potential but uncertain risk of pathological fracture. Management of MBD has become a major focus within orthopedic oncology with respect to fracture and impending fracture care. If impending skeletal-related events (SREs), particularly pathologic fracture, could be predicted, increasing evidence suggests that prophylactic surgical treatment improves patient outcomes. However, current fracture risk assessment and radiographic metrics do not have high accuracy and have not been combined with relevant patient survival tools. This review first explores the prevalence, incidence, and morbidity of MBD and associated SREs for different cancer types. Strengths and limitations of current fracture risk scoring systems for spinal stability and long bone fracture are highlighted. More recent computed tomography (CT)-based structural rigidity analysis (CTRA) and finite element (FE) analysis methods offer advantages of increased specificity (true negative rate), but are limited in availability. Other fracture prediction approaches including parametric response mapping and positron emission tomography/computed tomography measures show early promise. Substantial new information to inform clinical decision-making includes measures of survival, clinical benefits, and economic analysis of prophylactic treatment compared to after-fracture stabilization. Areas of future research include use of big data and machine learning to predict SREs, greater access and refinement of CTRA/FE approaches, combination of clinical survival prediction tools with radiographically based fracture risk assessment, and net benefit analysis for fracture risk assessment and prophylactic treatment.

Keywords: clinical decision making; fracture risk; metastatic bone disease; prophylactic stabilization; skeletal-related events.

Figure 1.

Components of Mirels’ scoring for long bones and SINS for metastatic bone lesions.

Figure 2.

Computed tomography rigidity analysis (CTRA) of 68yo male with a Mirels’ Score of 10. CTRA indicates a significant risk of fracture at the site of the lesion and was prophylactically stabilized. In this case, axial rigidity was reduced by more than 33% at the cross section of the lesion, indicating a high risk of fracture.

Figure 3.

CT based solid model of proximal femur (A) with a large intertrochanteric lytic defect (B). Elements are based on CT voxels (three dimensional pixels) (C) and material properties (elastic modulus shown here) of each element is based on CT mineral equivalent densities. Mechanical loading (D) can simulate different activities of daily living such as level walking or stair ascent. Reprinted from Goodheart et al.

Figure 4:

CT scan images of pre-experiment (A) and post axial load to failure (B) CT scans for three vertebral level construct. An experimental lesion was created for the middle vertebral body to simulate a metastatic lesion. White arrows indicate location of endplate fracture. Anterior (C) and lateral (D) views of specimen specific finite element models illustrate localization of failure to the middle vertebrae via plastic deformation (indicated in red/orange/yellow). Reprinted from Groenen et al..