Comparison of Local and Intravenous Zoledronic Acid on Histopathology and Recurrence Rate after Extended Curettage in Giant Cell Tumors of Proximal Tibia: A Prospective Study

Abstract

Introduction:

The bone pathology-giant cell tumor (GCT) is a locally aggressive and recurrent lesion. A bisphosphonate-zoledronic acid (ZA) has been known to lower the recurrence and resorption in similar bone lesions. Hence, we evaluated the effectivity of the ZA for the GCT of the proximal tibia.

Materials and Methods:

We piloted a prospective clinical observational study. We included 100 subjects with GCT, who were divided into two equal groups of case (given ZA) and control (no ZA). The histopathological features and the recurrence rates along with other findings were compared with P < 0.05 deliberated as significant.

Results:

We observed that for in the case group, calcification and fibrosis that were beneficial were observed. Reduced giant cells and lower recurrence rate are seen in the case group. No significant variation in the functional outcome was seen between the groups.

Conclusions:

ZA was shown to have beneficial effect on the outcome for the treatment of the GCT.

INTRODUCTION

The bone lesion-giant cell tumors (GCTs) are benign tumors that are locally aggressive and are known for their greater recurrence.[1,2,3] These are common in middle-aged women in the lower limbs, specifically femur. The pathology is related to the “receptor activator of nuclear factor kappa-B ligand (RANKL)” overexpression. These are very destructive lesions that will lead to loss of the function and also may lower the quality of life (QOL). Various reconstructive modalities have been suggested. A recurrence rate of as great as 50% is reported that may lower the QOL of the patients.[4,5,6] A bisphosphonate-zoledronic acid (ZA) has been known to lower the recurrence and resorption in similar bone lesions. ZA acts as an inhibitor of the osteoclast in other bone lesions and metastatic lesions. Hence, we evaluated the effectivity of the ZA for the GCT of the proximal tibia.

MATERIALS AND METHODS

We piloted a prospective clinical observational study. We included 100 subjects with GCT, who were divided into two equal groups of case (given ZA) and control (no ZA). The institutional ethics clearance and the subjects' consent were procured for the study. Age-matched subjects were selected for the study. The subjects were evaluated for the lesion size by computed tomography imaging. The ZA of 4 mg intravenous was given three times at a 21-day interval. Curettage was extensively carried out and the defect was closed with the autograft following all the standard protocols. The histopathology was compared at the different time zones, along with the size of the GCT, and the changes were noted by calculating the stromal cells: GC. The follow-up was done for a period of 3 years with a 3-month interval to estimate the recurrence rate and the functional betterment. The findings were compared with P < 0.05 deliberated as significant.

RESULTS

We observed no significant age or gender difference while the women were majority. The mean age was 45 years. Most lesions were grade II. Tumor size, calcification, fibrosis, osteoclastic cells, and stromal cells were significantly different for the two groups. Reduced giant cells and lower recurrence rate are seen in the case group. No significant variation in the functional outcome was seen between the groups [Table 1].

Table 1.

Comparison of the various parameters considered for the study (number of participants - n)

Parameter	Case	Control	P
Age	45±1.2	42±0.2	0.548
Gender (n)
Male	12	5	0.354
Female	38	45	0.258
Lesion “Campanacci grading” (n)
Grade I	13	11	0.147
Grade II	25	22
Grade III	12	17
Tumor size	Lowered in 21	Lowered in 8	0.04
Functional outcome (mean MSTS)	27±0.5	27±0.6	5.12
Recurrence rate (n)	1	3	0.89
Calcification - Increased, number of participants (n)	20	1	0.001
Fibrosis - Increased, number of participants (n)	14	2	0.02
Osteoclastic cells - Decreased, number of participants (n)	15	0	0.001
Stromal cells - Decreased with abnormal morphology, number of participants (n)	12	2	0.04

MSTS: Musculoskeletal Tumor Society

DISCUSSION

The osteoclastic inhibition of the bisphosphonates that affect the RANKL has been of recent interest. The ZA which is a bisphosphonate has been known to reduce the bone resorption and at the same time increasing the calcification and fibrosis. However, this is used in the cancer and metastasis treatment. Hence, in our study, we piloted to find the effect of ZA on GCT. We found that tumor size, calcification, fibrosis, osteoclastic cells, and stromal cells were significantly different for the two groups. Reduced giant cells and lower recurrence rate are seen in the case group. Previous studies have supported the ZA lowering the GC in metastatic tumors.[3,4,5,6,7,8] The same was observed in our study. The lower recurrence rate in our study is similar to the study of Tse et al., where they observed the recurrence in 1 out of 24 subjects.[4] The ZA is known to cause apoptosis of the osteoclastic cells.[4,5,6,7,8] Similar to our histological findings in the study of Arpornchayanon et al., ZA caused better calcification and almost no GCs were noted.[8]

There were few limitations in our study. Both the surgeon and the pathologist were aware of the subjects who were prescribed ZA that may cause a bias. The study was conducted in a single center.

CONCLUSIONS

The ZA has affected both the stromal and the osteoclastic cells in our study. These cells that are key to recurrence and lower bone quality, when treated, can bring about a good outcome. Hence, we suggest that ZA was beneficial in the treatment of the GCT. Further studies have to be planned to support our findings across various demographics.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.