Giant cell tumor (GCT) of bone is an osteolytic tumor that is locally aggressive and potentially metastatic. The pathogenesis of GCT is poorly understood. The purpose of this study was to harvest and culture primary cell lines from clinical specimens of GCT of bone and identify specific bone degradation proteases (matrix metalloproteinases: MMP-2, MMP-9) produced by the neoplastic stromal cells in vitro.

With approval by the McMaster University Biohazards and Ethics Review Boards, we acquired consent from five patients with GCT of bone, and harvested specimens intraoperatively. The specimens were chopped in DMEM containing 10% Fetal Bovine Serum, 2 mM L-glutamine, 100 U/ml penicillin and 100 mg/ml streptomycin. The cell suspensions were incubated at thirty-seven degrees (5% CO2 and 95% air) and cultivated. The cells were grown to confluence and taken through several passages until only proliferative cells were present. Immunocytochemistry with TRAP (Tartrate Resistant Acid Phosphatase) was used to confirm the stem cell origin of the propagative cells. Protein electrophoresis with embedded gelatin was used for detecting protease activity (MMP-2, MMP-9) on cell lysates and medium. P-aminophenyl mercuric acetate (APMA) was used to activate and ethylenediaminetetraacetic acid (EDTA) was used to block MMP-2 and MMP-9 activity. Our controls included serum free media, Human Osteosarcoma and Fibroblast cell lines.

Immunocytochemistry with TRAP confirmed that our propagative cells were not hematopoietic in origin but rather mesenchymal. Protein electrophoresis on cell lysates and medium identified the protease activity of MMP-2 and MMP-9 with lytic bands at appropriate molecular weights. APMA activated MMP-2 more than MMP-9, as indicated by increased relative density of bands. EDTA blocked the activity of both MMPs.

Our study confirmed the ability to cultivate the neoplastic stromal cells of GCT of bone from clinical specimens. Protein electrophoresis showed that activated MMP-2 and MMP-9 are secreted from the neoplastic stromal cells in vitro, suggesting a role for the tumor cells in bone destruction. These results are intriguing, as novel therapies in specific MMP inhibitors are currently underway for numerous disease processes.

Purpose: To determine the surgical and functional outcome of an anatomically based approach to hip reconstruction for metastatic bone disease.

Methods: Records of 123 consecutive patients who underwent hip arthroplasty for metastatic bone disease were reviewed. Sixty one patients (63 hips) had pelvic involvement that required periacetabular reconstruction. Sixty two patients (64 hips) had proximal femoral involvement but no acetabular disease. Operative technique was guided by the extent of column and dome disease in addition to the extent of involvement of the femur. Demographic variables, functional data (ECOG scores) and survival data were analyzed.

Results: : The cohort included 94 females and 29 males, mean age 62 years (range, 39–85). Breast, lung and kidney were the most common primary sites. The average time from initial primary diagnosis to surgery was 42 months. The average time from initial primary diagnosis to surgery was significantly longer for those with breast cancer compared to those with other primary sites (65 vs. 21 months, P< 0.001). Average blood loss was 788 ml (range, 200–3800 ml) and average operative time was 2.3 hours (range, 2–6 hours). There were three perioperative deaths. Functional scores improved from an average of 2.7 preoperatively to 1.4 postoperatively (P< 0.05). Two patients required closed reduction, two required open trochanteric repair and one required ace-tabular revision. Median survival time was 15 months (range, 0–172 months). Patients with breast cancer enjoyed longer survival compared to patients with other primaries (21 vs. 9 months, P=0.02).

Conclusions: Despite the moderate risk of operative complications, an anatomically based approach to reconstruction of metastatic hip disease is effective in improving functional outcome and quality of life in many patients.