title: Combination Therapy of Denosumab and Calcitriol for a Renal Transplant Recipient with Severe Bone Loss due to Therapy-Resistant Hyperparathyroidism.
abstract: Denosumab (DMAb), a complete human type monoclonal antibody directed against the receptor activator of nuclear factor-κB ligand, has gained attention as a novel treatment for osteoporosis. However, its efficacy in patients with chronic kidney disease (CKD) remains unclear. We describe a 64-year-old man with severe bone loss and persistent secondary hyperparathyroidism (SHPT) after renal transplantation, whose condition failed to respond to conventional pharmacologic or surgical interventions. He underwent parathyroidectomy with left forearm autograft of crushed tiny parathyroid gland (PTG) particles. However, the autografted PTGs became swollen and caused persistent SHPT in spite of two additional parathyroidectomies of the left forearm. A single subcutaneous administration of DMAb induced hypocalcemia, which was corrected by calcium supplementation and high-dose calcitriol. Eventually, combination therapy with DMAb and calcitriol led to a decline in the patient's elevated serum parathyroid hormone levels, normalization of laboratory markers of bone metabolism, and improvement in bone mineral density in a short period of time. To the best of our knowledge, this is the first case report of severe bone loss with persistent SHPT in a renal transplant recipient effectively treated with the combination therapy of DMAb and vitamin D (VD). Although DMAb itself exerts no direct effects on PTGs, the DMAb treatment improved the patient's bone loss. In addition, administration of DMAb allowed for high-dose VD therapy which ultimately controlled SHPT and prevented DMAb-induced hypocalcemia. Therefore, this combination therapy might be a reasonable therapeutic strategy to reverse severe bone loss due to therapy-resistant SHPT in patients with CKD.
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University School of Medicine.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Wada
authors.forename: Masayuki
authors.initials: M
authors.lastname: Iyoda
authors.forename: Ken
authors.initials: K
authors.lastname: Iseri
authors.forename: Noriko
authors.initials: N
authors.lastname: Arai-Nunota
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Saito
authors.forename: Toma
authors.initials: T
authors.lastname: Hamada
authors.forename: Shohei
authors.initials: S
authors.lastname: Tachibana
authors.forename: Misa
authors.initials: M
authors.lastname: Ikeda
authors.forename: Takanori
authors.initials: T
authors.lastname: Shibata
mesh_terms: D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002117:Calcitriol / Q000627:therapeutic use*; D000069448:Denosumab / Q000627:therapeutic use*; D004338:Drug Combinations; D006801:Humans; D006962:Hyperparathyroidism, Secondary; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy* / Q000209:etiology
chemical_list: D050071:Bone Density Conservation Agents; D004338:Drug Combinations; D000069448:Denosumab; D002117:Calcitriol