Patients with altered kidney function are at increased risk of hypocalcemia after denosumab administration. There is however a small number of studies and case reports describing hypocalcemia refractory to treatment. We describe a case of severe hypocalcemia, after the administration of three doses of denosumab, in a young patient with lupus nephritis under corticosteroid coverage and osteopenia. However, more studies are needed in order to extract a safe conclusion about the factors that contribute to the development of severe hypocalcemia in this group of patients.