title: Hypocalcemia post denosumab in patients with chronic kidney disease stage 4-5.
abstract: BACKGROUND
  Denosumab, a RANK-ligand inhibitor, is an effective treatment for osteoporosis in postmenopausal women and men. Unlike the bisphosphonates, it is not excreted by the kidney. Little is known, however, about its efficacy and safety in patients with severe chronic kidney disease (CKD).
  
  
  METHODS
  A retrospective study was performed in CKD 4-5D patients from a tertiary referral hospital who were treated with denosumab between 1st January 2011 and 31st March 2014. Data collected included information about the following: CKD stage, fracture history, bone mineral density, serum calcium levels pre and post denosumab treatment, episodes of hypocalcemia, relevant medications and adverse events.
  
  
  RESULTS
  Eight patients with CKD-5 and 6 patients with CKD-4 were identified (all female, mean age 77.1 ± 9.9). The mean pre-denosumab calcium value was 2.42 ± 0.12 mmol/l, PTH 20.2 ± 14.7 pmol/l and 25-OH vitamin D 69.1 ± 30.1 nmol/l. After denosumab treatment, 6/8 patients with CKD-5/5D, and 2/5 patients with CKD-4 developed severe hypocalcemia. Two patients developed direct adverse complications of hypocalcemia (seizure, laryngospasm, prolonged QTc). Among the patients who developed hypocalcemia, the median time to serum calcium nadir was 21 days and the median time to correction of hypocalcemia was 71 days. Treatment of hypocalcemia required large doses of oral calcium and calcitriol, and increases in dialysate calcium concentration.
  
  
  CONCLUSIONS
  A high rate of severe hypocalcemia was observed in patients with advanced CKD treated with denosumab. If denosumab is used in patients with severe CKD, close monitoring and aggressive replacement of calcium and calcitriol is required to avoid the development of hypocalcemia.
authors: Department of Nephrology, Austin Health, Heidelberg, Melbourne, Vic., Australia.
authors: Vatsa
authors: V
authors: Dave
authors: Cherie Y
authors: CY
authors: Chiang
authors: Jane
authors: J
authors: Booth
authors: Peter F
authors: PF
authors: Mount
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D002118:Calcium / Q000097:blood; D000069448:Denosumab / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006996:Hypocalcemia / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000188:drug therapy*; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000188:drug therapy; D012189:Retrospective Studies; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D050071:Bone Density Conservation Agents; D010281:Parathyroid Hormone; D014807:Vitamin D; D000069448:Denosumab; C104450:25-hydroxyvitamin D; D000469:Alkaline Phosphatase; D002118:Calcium