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

Abstract

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.

Giant Cell Tumor of Bone: Review of Current Literature, Evaluation, and Treatment Options

“…26 Kundu et al compared the efficacy of a preoperative zoledronic acid infusion in two surgicaltreated populations and found that that treated group had a lower recurrence rate along with improved surgical removal of the tumor. 27 Gouin et al prospectively evaluated the efficacy of postoperative zoledronic acid use after extensive curettage and found a low (15%) local recurrence rate. 28 Intravenous zoledronic acid appears to be effective with either pre-or postoperative utilization.…”

Effect of bisphosphonates on local recurrence of giant cell tumor of bone: a meta-analysis

“…Recently, there were some studies evaluating the effect of BPs on preventing postoperative recurrence of GCTB 23–29. However, to the best of our knowledge, there is no definite direction or consensus on the application of BPs in GCTB.…”

Adjuvant Zoledronic Acid in High-Risk Giant Cell Tumor of Bone: A Multicenter Randomized Phase II Trial

“…Recurrences were seen in 1 out of 18 patients in the zoledronic acid group and 4 out of 19 patients in the control group ( p = .47). Curettage tissue showed a decrease in stromal cells and increased calcification in the zoledronic acid group .…”

“…The benefit of adjuvant zoledronic acid, as well as optimal timing and duration of zoledronic acid treatment, is yet to be determined. The improved mineralization and marginalization leading to easier curettage advocates the use of zoledronic acid in the neoadjuvant setting. In a recent comparative prospective study extended curettage was performed in 37 patients with GCTB with or without three preoperative zoledronic acid infusions (4 mg) at 3‐week intervals.…”