LAUSR

INTRODUCTION Pathologic vertebral fractures are a major clinical concern in the management of cancer patients with metastatic spine disease. These fractures are a direct consequence of the effect of bone metastases on the anatomy and structure of the vertebral bone. The goals of this study were twofold. First, we evaluated the effect of lytic, blastic and mixed (both lytic and blastic) metastases on the bone structure, on its material properties, and on the overall vertebral strength. Second, we tested the ability of bone mineral content (BMC) measurements and standard FE methodologies to predict the strength of real metastatic vertebral bodies. METHODS Fifty-seven vertebral bodies from eleven cadaver spines containing lytic, blastic, and mixed metastatic lesions from donors with breast, esophageal, kidney, lung, or prostate cancer were scanned using micro-computed tomography (μCT). Based on radiographic review, twelve vertebrae were selected for nanoindentation testing, while the remaining forty-five vertebrae were used for assessing their compressive strength. The μCT reconstruction was exploited to measure the vertebral BMC and to establish two finite element models. 1) a micro finite element (μFE) model derived at an image resolution of 24.5 μm and 2) homogenized FE (hFE) model derived at a resolution of 0.98 mm. Statistical analyses were conducted to measure the effect of the bone metastases on BV/TV, indentation modulus (Eit), ratio of plastic/total work (WPl/Wtot), and in vitro vertebral strength (Fexp). The predictive value of BMC, μFE stiffness, and hFE strength were evaluated against the in vitro measurements. RESULTS Blastic vertebral bodies exhibit significantly higher BV/TV compared to the mixed (p = 0.0205) and lytic (p = 0.0216) vertebral bodies. No significant differences were found between lytic and mixed vertebrae (p = 0.7584). Blastic bone tissue exhibited a 5.8% lower median Eit (p< 0.001) and a 3.3% lower median Wpl/Wtot (p<0.001) compared to non-involved bone tissue. No significant differences were measured between lytic and non-involved bone tissues. Fexp ranged from 1.9 to 13.8 kN, was strongly associated with hFE strength (R2=0.78, p< 0.001) and moderately associated with BMC (R2=0.66, p< 0.001) and μFE stiffness (R2=0.66, p< 0.001), independently of the lesion type. DISCUSSION Our findings show that tumour-induced osteoblastic metastases lead to slightly, but significantly lower bone tissue properties compared to controls, while osteolytic lesions appear to have a negligible impact. These effects may be attributed to the lower mineralization and woven nature of bone forming in blastic lesions whilst the material properties of bone in osteolytic vertebrae appeared little changed. The moderate association between BMC- and FE-based predictions to fracture strength suggest that vertebral strength is affected by the changes of bone mass induced by the metastatic lesions, rather than altered tissue properties. In a broader context, standard hFE approaches generated from CTs at clinical resolution are robust to the lesion type when predicting vertebral strength. These findings open the door for the development of FE-based prediction tools that overcomes the limitations of BMC in accounting for shape and size of the metastatic lesions. Such tools may help clinicians to decide whether a patient needs the prophylactic fixation of an impending fracture.