Artikel
Efficacy of Denosumab with special reference to its role in joint preservation as an adjuvant in the management of Giant Cell Tumor of bone
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Veröffentlicht: | 5. Oktober 2015 |
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Objectives: Giant Cell Tumors of bone (GCTB) are aggressive primary bone tumors causing progressive osteolysis, most commonly in periarticular locations, thereby putting the adjacent joint at risk. Histologically, GCTB are composed of osteoclast-like Giant Cells that are activated by the neoplastic stromal cells via the RANK/RANKL and OPG (osteoprotegerin) pathway and leading to extensive bone resorption. Denosumab, a human monoclonal antibody which specifically targets RANKL, inhibits this process and eliminates giant cells. This is thought to potentially allow for remineralization of the osteolytic cavity, particularly the subchondral bone and the residual thin and expanded cortex, often referred to as a neocortex. These potential bony changes following denosumab treatment would facilitate joint preservation surgery, especially in cases where significant thinning, breech or fracture through the surrounding neocortex or subchondral bone would otherwise necessitate more radical surgery.
Methods: This is a prospective non-randomized study conducted in 20 patients with histologically proven GCT of bone. All patients consented to receiving Denosumab as an adjuvant before definite surgery. Patients received an initial loading dose of denosumab (120 mg) subcutaneously on days 1,8,15 and 29 and then every 4 weeks for a minimum of 6 month. Serial radiographs were used to monitor response to treatment. Histological response was evaluated postoperatively.
Results and Conclusion: All 20 patients finished the trial and were available at the time of final evaluation. The patients received an average of 8.8 doses denosumab (median 8, Range 8-13). During the first month of treatment all patients reported a significant decrease of pain, after 6 month 16 patients reported to be pain free. Six patients (30%) reported grade 1 or 2 adverse events (Fatique, Headache, Nausea, Arthralgia), in two patients a transient hypocalcaemia was detected. No severe adverse events were reported. Prior the denosumab treatment in 15 patients a joint preservation was uncertain. In 17 patients a joint preserving operation could be performed. All pathological fractures healed during the course of medical treatment.In summary a partial radiological tumour response to denosumab was noted in all patients (size, sclerosis, osteoinduction, cortical thickness). No post-operative complications were observed. Median follow-up time was 19 month (9 ? 34 month).Local recurrence occurred in three patients (15%) 10, 12 and 25 month after intralesional curettage.
Denosumab appears to be a useful adjuvant in the treatment of patients with GCTB especially to facilitate joint preservation and reduce explicitly the extent of surgery.Denosumab provides consistent and favorable response referred to improvement of clinical symptoms, diminish of osteoclast-like giant cells, formation of mineralized woven bone, improvement of subchondral plate and cortical thickness. Local recurrence of rate GCTB seems not affected by denosumab.