Effect of recombinant human bone morphogenetic protein‐2 on a novel lung cancer spine metastasis model in rodents

Abstract

Lung cancer is the second most prevalent cancer. Spinal metastases are found in 30-90% of patients with death attributed to cancer. Due to bony destruction caused by metastases, surgical intervention is often required to restore spinal alignment and stability. While some research suggests that BMP-2 may possess tumorigenic effects, other studies show possible inhibition of cancer growth. Thirty-six athymic rats underwent intraosseous injection of lung adenocarcinoma cells into the L5 vertebral body. Cells were pre-treated with vehicle control (Group A) or rhBMP-2 (Group B) prior to implantation. At 4 weeks post-implantation, in vivo bioluminescent imaging (BLI) was performed to confirm presence of tumor and quantify signal. Plain radiographs and microComputed Tomography (microCT) were employed to establish and quantitate osteolysis. Histological analysis characterized pathologic changes in the vertebral body. At 4 weeks post-implantation, BLI showed focal signal in the L5 vertebral body in 93% of Group A animals and 89% of Group B animals. Average tumor burden by BLI radiance was 7.43 Â 10 3 p/s/cm 2 /sr (Group A) and 1.11 Â 10 4 p/s/cm 2 /sr (Group B). Radiographs and microCT demonstrated osteolysis in 100% of animals showing focal BLI signal. MicroCT demonstrated significant bone loss in both groups compared to age-matched controls but no difference between study groups. Histological analysis confirmed tumor invasion in the L5 vertebral body. These findings provide a reliable in vivo model to study isolated spinal metastases from lung cancer. Statement of Clinical Significance: The data support the notion that exposure to rhBMP-2 does not promote the growth of A549 lung cancer spine lesions. ß

Bone graft options for spinal fusion following resection of spinal column tumors: systematic review and meta-analysis

“…While a recent meta-analysis by Cahill et al 11 revealed that there was no conclusive evidence that BMP-2 was associated with the formation of cancer locally or at a distant site, there remains concern regarding its potential carcinogenicity. 58,62,63,66 Although the use of local bone grafts are relatively contraindicated following spinal column tumor resection, patients in 3 studies 19,41,54 received morselized local bone grafts. Of note, Coumans et al 19 reported the use of a vertebral autograft that contained tumor, after the diagnosis of benign intraosseous schwannoma was confirmed by intraoperative pathological diagnosis.…”

“…8,9,27,31,40 Additionally, although controversial, the application of bone morphogenetic protein-2 (BMP-2) to patients with tumors is generally contraindicated due to several prior studies that suggested an increased incidence of tumors in patients who received BMP-2. 58,62,63,66 Because of these issues, it is unclear what bone graft options should be selected in patients with spinal column tumors. The literature is also significantly limited, as a majority of prior reports were either retrospective with small numbers of patients, 1,36 or case reports, 5 focusing on survival outcomes or technical aspects of surgery rather than fusion outcomes.…”

Deep Learning on MRI Images for Diagnosis of Lung Cancer Spinal Bone Metastasis

“…The emergence of bone metastasis indicates a shortened survival period and a serious decline in the quality of life of patients. In the treatment of lung cancer, the prevention and treatment of bone metastasis are also particularly important [ 5 ].…”