Morphological, histomorphometric, and microstructural alterations in human bone metastasis from breast carcinoma
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abstract
Bone is one of the most common sites of breast cancer metastasis. Metastases are often associated with bone destruction and are a major cause of morbidity. We examined structural bone changes induced by metastatic tumor in bone biopsies from 33 patients with metastatic breast carcinoma (20 from patients with pathological femoral fracture and 13 with no fracture) and 20 normal controls. In all metastatic biopsies bone remodeling was shown to be tumor volume-dependent. Bone resorption and bone formation were biphasic with both increasing at earlier stages of metastatic bone disease and decreasing later on. A comparison of patients with fracture and no fracture did not reveal statistically significant differences in the extent of bone destruction or trabecular thinning. Bone histomorphometry showed limited ability to explain the higher bone volume loss in fracture patients (decreases of 42% and 25%, respectively, in fracture and nonfracture patients compared with controls). However, changes in bone quality, including increased disconnectivity and decreased connectivity, as evaluated by node-strut analysis, suggested that there were more structural changes in the fracture compared with the nonfracture group. The nonfracture group included six patients with no radiological evidence of bone metastasis (occult metastasis). They showed a higher tumor volume and a twofold lower eroded surface compared with the rest of the group. The decrease in bone volume (14% lower than controls) was below the limit of X-ray detection. Because we observed no increase in osteoclast-related parameters and no correlation between osteoclast surface and eroded surface, we believe that, in occult metastasis, osteoclastic bone resorption is not an important factor in overall bone resorption. Quantitatively, the eroded surface in direct contact with tumor cells was threefold higher than the osteoclast surface in occult metastasis, whereas the rest of the metastatic group (27 of 33) showed predominantly osteoclast-mediated eroded surface. Node-strut analysis on occult metastasis revealed a significant increase in disconnectivity without a concomitant significant decrease in bone volume and trabecular thinning. We conclude that, in occult metastasis, bone resorption may be more osteoclast-independent and other mechanisms involving the tumor cells may be more prevalent.
