Context: The effect of PTH therapy on serum and urinary calcium levels and the risk of hypercalcemia or hypercalciuria has not been formally evaluated.

Objective: 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.

Design, Setting, Participants and Intervention: 178 postmenopausal women randomized to either PTH(1-84) alone or in combination with alendronate during the first year of the PaTH study.

Main Outcome: Fasting serum calcium at baseline, 1, 3, and 12 months; 24-hour urinary calcium at baseline and 3 months.

Results: 14% of participants developed serum calcium > 10.5 mg/dl (> 2.6 mmol/L). 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 intravenous hydration and PTH discontinuation. Baseline characteristics associated with the development of hypercalcemia were serum calcium (Relative Hazards [RH] = 1.9 per 0.5 mg/dl [0.12 mmol/L]; 95% confidence interval [95%CI] = 1.1-3.2) and serum 1,25-dihydroxyvitamin D (RH = 1.9 per 10 pg/ml [26 pmol/L]; 95%CI = 1.2-3.1). Fifteen women (8%) developed hypercalciuria (urinary calcium > 400 mg (100 mmol)/24 hours 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 (RH = 1.5 per 50 mg/day [12.5 mmol/day]; 95%CI = 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 22%. 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.