Effect of Intravenous Zoledronic Acid on Histopathology and Recurrence after Extended Curettage in Giant Cell Tumors of Bone: A Comparative Prospective Study

BACKGROUND: Giant cell tumor (GCT) of the bone is known for its locally aggressive behavior and tendency to recur. It is an admixture of rounded or spindle-shaped mononuclear neoplastic stromal cells and multinucleated osteoclast-like giant cells with their proportionate dispersion among the former. Zoledronic acid (a bisphosphonate) is being used in various cancers such as myelomas and metastasis, for osteoporosis with an aim to reduce the resorption of bone, and as an adjuvant treatment for the management of GCT of bone for reduction of local recurrence. We have carried out a prospective comparative study to assess the effect of intravenous infusion of zoledronic acid on histopathology and recurrence of GCT of bone. MATERIALS AND METHODS: The study was carried out in the biopsy proven GCTs in 37 patients; 15 males and 22 females, in the age range from 17 to 55 years. They were treated with extended curettage. Of these 37 patients, 18 were given three doses of 4 mg zoledronic acid infusion at 3-week intervals and extended curettage was performed 2 weeks after the last infusion whereas the other 19 were treated with extended curettage without zoledronic infusion. The post infusion histopathology of the curetted material was compared with the histopathology of initial biopsy. All the patients were evaluated at 3-month intervals for the first 2 years and then six monthly thereafter, for local recurrence and functional outcome of limb using the Musculoskeletal Tumor Society (MSTS) score. RESULTS: In postzoledronic infusion cases, the histopathology of samples showed abnormal stromal cells secreting matrix leading to fibrosis and calcification. The type of fibrosis and calcification was different from pathological calcification and fibrosis what is usually observed. There was a good marginalization and solidification of tumors which made surgical curettage easier in six cases in the study group. There was noticeable reduction in the number of giant cells and alteration in morphology of stromal cells to the fibroblastic-fibrocytic series type in comparison to preinfusion histopathology. Recurrence occurred in one case out of 18 patients in infusion group whereas in four cases among 19 patients in control group. The functional results were assessed, and the overall average MSTS score was 27.50 (range 24–30) and 27.00 (range 23.50–30) in the study and control groups, respectively. CONCLUSIONS: We observed that bisphosphonates reduce osteoclast activity and affects stromal cells in GCT, resulting in the reduction of their numbers and noticeable apoptosis. This results in better marginalization of the lesions and reduced recurrence. Extended curettage of friable GCT became easier and adequate which otherwise might not have been possible.