I read with much interest the article by Tabrizi et al. reporting their clinical trial, which was published in your esteemed journal. This clinical trial contrasted the effect of receiving calcitonin salmon nasal spray 200 IU/day once a day for 3 months and placebo in patients who underwent curettage of aggressive central giant cell granulomas (CGCGs).

However, Tabrizi et al. have overlapped CGCGs with giant cell tumours (GCT). Although both lesions share a histopathological dominance of osteoclast-like giant cells, the giant cells in both CGCG and GCT are not neoplastic. The neoplastic cells, which demonstrate high mitotic figures, are even mononuclear. Moreover, unlike GCTs, CGCGs reveal neither high stromal cellularity nor necrosis. Cytogenetically, CGCGs do not demonstrate recurrent p.Gly34 Trp or p.Gly34 Leu mutations in the H3F3A gene. However, the H3F3A mutation is evident, almost specifically, in GCT.

Based on this confusion between the two diseases, Tabrizi et al. have attributed the efficacy of calcitonin therapy to targeting the calcitonin receptors in CGCGs: “Two distinct DNAs encoding the CTRs on CGCGs”, as ‘concluded’ by Gorn et al. However, Gorn et al. studied cloned GC-2 and GC-10 of a GCT of bone. To reiterate, CGCG is neoplastically different from GCT, and Gorn et al. studied no CGCGs.

Also, Tabrizi et al. claimed that the use of calcitonin nasal spray, as an adjunctive treatment, is superior to subcutaneous injections, except for the decreased absorption of nasal sprays. However, de Lange et al., in an earlier publication, concluded that calcitonin nasal spray was less effective than subcutaneous injections. Moreover, the calcitonin nasal spray dose did not yield sufficiently favourable clinical results (except for some mild calcification) or radiological results to spare the patients from a surgical procedure.

To conclude, the results of the study by Tabrizi et al. must be viewed with extreme caution, given the confusion between the two similar diseases and the lack of histological photomicrographs of the CGCGs investigated in that study. This confusion could have an undesirable clinical impact unless the difference between GCTs and CGCGs is adequately emphasized.