title: Elevations in serum and urinary calcium with parathyroid hormone (1-84) with and without alendronate for osteoporosis.
abstract: BACKGROUND
  The effect of PTH therapy on serum and urinary calcium levels and the risk of hypercalcemia or hypercalciuria has not been formally evaluated.
  
  
  OBJECTIVE
  The objective was to examine changes in serum and urinary calcium associated with PTH(1-84) therapy in the PaTH trial and the extent to which a defined algorithm resolved the elevated values.
  
  
  METHODS
  A total of 178 postmenopausal women were randomized to PTH(1-84) either alone or in combination with alendronate during the first year of the PaTH study.
  
  
  METHODS
  The main outcome measures were fasting serum calcium at baseline and 1, 3, and 12 months and 24-h urinary calcium at baseline and 3 months.
  
  
  RESULTS
  In 14% of participants, serum calcium more than 10.5 mg/dl (>2.6 mmol/liter) developed. Following the defined algorithm, 58% of elevated measurements were normal on repeat testing; 38% required discontinuation of calcium and vitamin D supplementation, and one necessitated a decrease in PTH injection frequency to normalize serum calcium. One participant developed transient hypercalcemia between study visits and required hospitalization; the episode resolved with iv hydration and PTH discontinuation. Baseline characteristics associated with the development of hypercalcemia were serum calcium [relative hazards = 1.9 per 0.5 mg/dl (0.12 mmol/liter); 95% confidence interval = 1.1-3.2] and serum 1,25-dihydroxyvitamin D [relative hazard = 1.9 per 10 pg/ml (26 pmol/liter); 95% confidence interval = 1.2-3.1]. Fifteen women (8%) developed hypercalciuria [urinary calcium > 400 mg (100 mmol)/24 h or calcium/creatinine ratio > 0.4]; 80% of cases resolved after discontinuing calcium and vitamin D, 13% without intervention, and one after PTH injection frequency was decreased. Higher baseline urinary calcium excretion was associated with development of hypercalciuria [relative hazard = 1.5 per 50 mg/d (12.5 mmol/d); 95% confidence interval = 1.2-4.0]. Proportions of patients with elevated serum and urinary calcium were similar on single and combination therapy.
  
  
  CONCLUSIONS
  The frequency of episodic hypercalcemia or hypercalciuria in the PaTH trial was 21%. Episodes were generally mild, and nearly all cases resolved spontaneously or with discontinuation of calcium and vitamin D. The algorithms used to address hypercalcemia and hypercalciuria in the PaTH trial proved effective in safely resolving clinical episodes of increased urinary or serum calcium and might therefore be helpful to clinicians caring for patients on PTH.
authors.affiliation: Division of Endocrinology, Department of Medicine, University of California, San Francisco, California 94107, USA.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Antoniucci
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Sellmeyer
authors.forename: John P
authors.initials: JP
authors.lastname: Bilezikian
authors.forename: Lisa
authors.initials: L
authors.lastname: Palermo
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Ensrud
authors.forename: Susan L
authors.initials: SL
authors.lastname: Greenspan
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Black
mesh_terms: D000368:Aged; D019386:Alendronate / Q000008:administration & dosage* / Q000009:adverse effects; D000465:Algorithms; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects; D002118:Calcium / Q000097:blood* / Q000652:urine*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000139:chemically induced; D053565:Hypercalciuria / Q000139:chemically induced; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D010281:Parathyroid Hormone / Q000008:administration & dosage* / Q000009:adverse effects; D010919:Placebos
chemical_list: D050071:Bone Density Conservation Agents; D010281:Parathyroid Hormone; D010919:Placebos; D002118:Calcium; D019386:Alendronate