Cadmium in bone cement induces necrosis and decreases the viability of residual osteosarcoma cells: A xenograft study

Abstract

Objective: The aim of this study was to show whether local application of cadmium-impregnated bone cement can induce apoptosis and decrease the viability of residual osteosarcoma (OS) cells in nude mice.

Methods: K7M2 tumorigenic OS cell line was cultivated in vitro. The xenograft tumor model was formed by subcutaneously adding the tumor cells to athymic nude mice. Tumor was formed within 1 month. Then, mice were randomly assigned to five groups, each containing seven nude mice: control (group 1), wide resection (group 2), intralesional resection (group 3), intralesional resection + bone cement (group 4), and intralesional resection + cadmium embedded in bone cement (group 5). Tumor resection with 1 cm surgical margins was performed in the wide resection group. In intralesional resection groups, tumor tissue was resected with positive margins aiming to leave 15 mm3 of macroscopic tumor tissue. In group 3, the defect was left empty; groups 4 and 5 received bone cements prepared with saline and cadmium solutions, respectively. After the resection, mice were observed for 15 days and sacrificed. Next, surgical resection sites were evaluated histopathologically in each group.

Results: Recurrent tumor was formed in all mice in the wide resection group, and apparent progression of residual tumor was observed in groups 3 and 4. On the contrary, only a thin layer of residual tumor was observed around the bone cement in group 5. Histological evaluation revealed remarkable necrosis in group 5 and lowest viability compared to other groups. No systemic toxic effect related to cadmium was observed.

Conclusion: Our data suggest that local application of cadmium in bone cement has a significant potential to increase tumor necrosis and decrease the viability of residual OS cells.

Figure 1

Appearance of primary tumor in the control group (right); and residual tumor lesion (left) 15 days after intralesional resection

Figure 2

Appearance of residual tumor lesion in intralesional excision + cement with SF group (T: tumor, C: cement)

Figure 3

Appearance of residual tumor lesion in intralesional resection + cement with cadmium group. (T: tumor, C: cement). Note the thinner formation of tumor compared to the residual tumor in Figure 2

Figure 4. a–i

Tumor tissue microscopic sections, (a) Control group; the vascularized aggressive, muscle invasive undifferentiated tumor tissue. (b, c) Intralesional excision group, b: primary tumor, c: Residual tumor at the same site after 2 weeks. Both tumors were aggressive and invasive similar to control group. (d, e) Wide excision group. d: primary tumor and e: recurrent tumor. Although wide excision with 1 cm surgical margins was performed recurrence occurred in all seven nude mice. (f, g) Cement with SF applied after intralesional excision group. f: primary tumor. g: residual tumor around bone cement after 2 weeks. (h, i) Cement with Cadmium applied after intralesional excision group. h: primary tumor. I: residual tumor around cement after 2 weeks showing prominent necrosis

Figure 5. a–d

Microscopic sections of organs in cement + cadmium group. (a) Liver. (b) Kidney. (c) Lung. (d) Brain. The microscopic examinations showed no pathological changes. Local administration of cadmium did not cause any systemic effects