title: Effects of Denosumab and Calcitriol on Severe Secondary Hyperparathyroidism in Dialysis Patients With Low Bone Mass.
abstract: BACKGROUND
  Secondary hyperparathyroidism (SHPT) may worsen with administration of denosumab in chronic renal failure patients with low bone mass.
  
  
  OBJECTIVE
  This study aimed to evaluate the short-term effect of coadministration of calcitriol and denosumab on PTH secretion and parathyroid structure and the incidence of adverse effects in patients with SHPT and low bone mass.
  
  
  METHODS
  This was a 24-week, open-label study at Kaohsiung Veterans General Hospital in Kaohsiung, Taiwan.
  
  
  METHODS
  Dialysis patients with SHPT (intact parathyroid hormone [iPTH] > 800 pg/mL) and low bone mass (T score < -2.5) were enrolled.
  
  
  METHODS
  Patients received denosumab (60 mg) and doses of calcitriol adjusted to achieve iPTH < 300 pg/mL.
  
  
  METHODS
  Parathyroid gland volume was assessed upon study initiation and completion. Serum calcium, phosphate, alkaline phosphatase, iPTH, and adverse effects were assessed at each visit (Day 7, 14, and 21, and every month thereafter).
  
  
  RESULTS
  iPTH significantly decreased (mean decrease, 58.28 ± 6.12%) with denosumab/calcitriol administration (P < .01) but not in the controls (patients not receiving denosumab). Parathyroid gland volume decreased (mean decrease, 21.98 ± 5.54%) with denosumab/calcitriol administration (P < .01) and progressively increased (20.58 ± 4.48%) in the controls (P < .05). Serum alkaline phosphatase and iPTH levels were significantly correlated to decreased iPTH and regression of parathyroid hyperplasia (P < .05). The most common adverse events were hypocalcemia (33.33%) and respiratory tract infection (4.17%). Hypocalcemia rapidly resolved with calcium and calcitriol supplements.
  
  
  CONCLUSIONS
  Denosumab allows for supra-physiologic doses of calcitriol resulting in decreased parathyroid secretion and parathyroid hyperplasia. Supervised administration and weekly laboratory and clinical monitoring of serum calcium are recommended during the first month to prevent hypocalcemia.
authors.affiliation: Division of Nephrology (C.-L.C., C.-Y.H., K.-J.C., H.-C.F., P.-T.L.), Kaohsiung Veterans General Hospital, 81362 Kaohsiung, Taiwan; Department of Neurology (N.-C.C.), Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 83301 Kaohsiung, Taiwan; Department of Radiology (H.-L.L.), Kaohsiung Veterans General Hospital, 81362 Kaohsiung, Taiwan; and Department of Medicine (C.-L.C., H.-L.L., C.-Y.H., K.-J.C., H.-C.F., P.-T.L.), National Yang-Ming University School of Medicine, 11221 Taipei, Taiwan.
authors.forename: Chien-Liang
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Division of Nephrology (C.-L.C., C.-Y.H., K.-J.C., H.-C.F., P.-T.L.), Kaohsiung Veterans General Hospital, 81362 Kaohsiung, Taiwan; Department of Neurology (N.-C.C.), Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 83301 Kaohsiung, Taiwan; Department of Radiology (H.-L.L.), Kaohsiung Veterans General Hospital, 81362 Kaohsiung, Taiwan; and Department of Medicine (C.-L.C., H.-L.L., C.-Y.H., K.-J.C., H.-C.F., P.-T.L.), National Yang-Ming University School of Medicine, 11221 Taipei, Taiwan.
authors.forename: Nai-Ching
authors.initials: NC
authors.lastname: Chen
authors.affiliation: Division of Nephrology (C.-L.C., C.-Y.H., K.-J.C., H.-C.F., P.-T.L.), Kaohsiung Veterans General Hospital, 81362 Kaohsiung, Taiwan; Department of Neurology (N.-C.C.), Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 83301 Kaohsiung, Taiwan; Department of Radiology (H.-L.L.), Kaohsiung Veterans General Hospital, 81362 Kaohsiung, Taiwan; and Department of Medicine (C.-L.C., H.-L.L., C.-Y.H., K.-J.C., H.-C.F., P.-T.L.), National Yang-Ming University School of Medicine, 11221 Taipei, Taiwan.
authors.forename: Huei-Lung
authors.initials: HL
authors.lastname: Liang
authors.affiliation: Division of Nephrology (C.-L.C., C.-Y.H., K.-J.C., H.-C.F., P.-T.L.), Kaohsiung Veterans General Hospital, 81362 Kaohsiung, Taiwan; Department of Neurology (N.-C.C.), Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 83301 Kaohsiung, Taiwan; Department of Radiology (H.-L.L.), Kaohsiung Veterans General Hospital, 81362 Kaohsiung, Taiwan; and Department of Medicine (C.-L.C., H.-L.L., C.-Y.H., K.-J.C., H.-C.F., P.-T.L.), National Yang-Ming University School of Medicine, 11221 Taipei, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: Division of Nephrology (C.-L.C., C.-Y.H., K.-J.C., H.-C.F., P.-T.L.), Kaohsiung Veterans General Hospital, 81362 Kaohsiung, Taiwan; Department of Neurology (N.-C.C.), Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 83301 Kaohsiung, Taiwan; Department of Radiology (H.-L.L.), Kaohsiung Veterans General Hospital, 81362 Kaohsiung, Taiwan; and Department of Medicine (C.-L.C., H.-L.L., C.-Y.H., K.-J.C., H.-C.F., P.-T.L.), National Yang-Ming University School of Medicine, 11221 Taipei, Taiwan.
authors.forename: Kang-Ju
authors.initials: KJ
authors.lastname: Chou
authors.affiliation: Division of Nephrology (C.-L.C., C.-Y.H., K.-J.C., H.-C.F., P.-T.L.), Kaohsiung Veterans General Hospital, 81362 Kaohsiung, Taiwan; Department of Neurology (N.-C.C.), Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 83301 Kaohsiung, Taiwan; Department of Radiology (H.-L.L.), Kaohsiung Veterans General Hospital, 81362 Kaohsiung, Taiwan; and Department of Medicine (C.-L.C., H.-L.L., C.-Y.H., K.-J.C., H.-C.F., P.-T.L.), National Yang-Ming University School of Medicine, 11221 Taipei, Taiwan.
authors.forename: Hua-Chang
authors.initials: HC
authors.lastname: Fang
authors.affiliation: Division of Nephrology (C.-L.C., C.-Y.H., K.-J.C., H.-C.F., P.-T.L.), Kaohsiung Veterans General Hospital, 81362 Kaohsiung, Taiwan; Department of Neurology (N.-C.C.), Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 83301 Kaohsiung, Taiwan; Department of Radiology (H.-L.L.), Kaohsiung Veterans General Hospital, 81362 Kaohsiung, Taiwan; and Department of Medicine (C.-L.C., H.-L.L., C.-Y.H., K.-J.C., H.-C.F., P.-T.L.), National Yang-Ming University School of Medicine, 11221 Taipei, Taiwan.
authors.forename: Po-Tsang
authors.initials: PT
authors.lastname: Lee
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology* / Q000627:therapeutic use; D000069448:Denosumab; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D010280:Parathyroid Glands / Q000000981:diagnostic imaging; D010281:Parathyroid Hormone / Q000097:blood; D006435:Renal Dialysis; D012720:Severity of Illness Index; D014463:Ultrasonography
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D010281:Parathyroid Hormone; D000069448:Denosumab; D002117:Calcitriol