Current indications for denosumab in benign bone tumours.

Denosumab is a fully humanised monoclonal antibody to RANK ligand, inhibiting the RANK-RANKL pathway. It promotes the apoptosis of osteoclast-like giant cells, a secondary ossification and connective tissue formation. Given its high efficacy, denosumab is the standard treatment of unresectable or metastatic giant cell tumour of bone (GCTB) requiring morbid surgery. Neoadjuvant administration of denosumab may be justified to enable the resection of the tumour in certain cases; it should be considered, however, with caution for joint-saving surgery due to high local recurrence rates. In cases of unresectable or metastatic GCTB, however, denosumab treatment should be administered for years or even as a lifelong therapy. This poses many yet unanswered questions concerning the frequency of denosumab treatment as well as the ratio of the adverse events in the following years. Denosumab suppresses, not directly targets, the neoplastic stromal cells of GCTB. Ongoing in vitro studies suggest that other drugs alone or in combination (e.g. sunitinib) with denosumab may target both the neoplastic and the giant cells. Promising results have been reported regarding the off-label use of denosumab in other giant cell-rich tumours/tumour-like lesions, i.e. aneurysmal bone cysts and central giant cell granulomas. Data are derived, however, mostly from case reports and case series. Large prospective clinical trials are needed to evaluate the role and also the side effects of denosumab in the treatment of these rare diseases.

[Juvenile haemochromatosis presenting as intractable congestive heart failure]. / Intractabilis szívelégtelenséget okozó juvenilis haemochromatosis.

Juvenile haemochromatosis is an autosomal, recessive inherited iron metabolism disorder. The rapid deterioration and malignant prognosis differentiate juvenile haemochromatosis from hereditary haemochromatosis. The authors summarize the history of a 25 year old man, who worked in Hungary as a guest worker living in Romania. No significant illness has occurred in his previous history. The abdominal pain was his first symptom and he was treated in different institutions, where cholecystitis, alcoholic hepatic disease, hepatic cirrhosis were considered as a cause of his symptoms. Some weeks later atrial tachycardia, and congestive heart failure were observed and he was sent to our Cardiology Department. The echocardiography revealed diffuse hypokinesis, serious systolic dysfunction (ejection fraction: 21%), grade II mitral and tricuspid insufficiency with pulmonary hypertension. Considering the rapid deterioration of his cardiac function, myocarditis was suspected. Myocardial biopsy and coronary arteriography were performed. Coronary arteries were normal. Ventricular fibrillation occurred during coronary arteriography. Myocardial biopsy revealed juvenile haemochromatosis. Special laboratory examinations (transferrin saturation) were made after biopsy, that also confirmed the diagnosis of juvenile haemochromatosis. Cardiac transplantation was planned. Some days after the diagnosis was made the patient died of cardiogenic shock and intractable heart failure. Autopsy revealed hypogonadism and serious haemochromatosis in different parenchymal organs. Juvenile haemochromatosis should be considered in every young patient with congestive heart failure of unknown etiology.