Context: Teriparatide [TPTD, rhPTH(1-34)] given subcutaneously once daily transiently increases serum calcium concentrations at 4 to 6 hours after dosing, but its effects on urinary calcium excretion are less well studied.

Objective: To evaluate urinary calcium excretion, a pre-specified safety endpoint, for up to 12 months of TPTD treatment.

Design: Two prospective, randomized, double-blind placebo-controlled clinical trials.

Participants: A total of 2074 participants with osteoporosis or low bone mass (Study I, 1637 postmenopausal women; Study II, 437 men).

Interventions: Participants were given calcium (1000 mg/d) and vitamin D (400-1200 IU/d) supplements, and were randomized to placebo, TPTD 20 µg/d, or 40 µg/d (PL, TPTD20, TPTD40).

Main Outcome Measures: Urinary calcium excretion was measured in 24-hour collections at baseline, 1, 6, and 12 months.

Results: In each study, baseline urinary calcium excretion was similar between groups. All groups had significantly increased urinary calcium excretion, compared with baseline, at most post-baseline time points. Post-baseline urinary calcium excretion was increased in the TPTD20 group by up to 32 mg/d compared to placebo at the same time point (P<0.05) in Study I. A total of 7 participants (0.3%), of which 3 and 4 were in the placebo and TPTD groups, respectively, discontinued study drug due to repeated hypercalciuria (>300 mg/d).

Conclusion: Urinary calcium excretion was increased with TPTD treatment for up to 12 months, compared to placebo and baseline values, but the magnitude of these changes is unlikely to be clinically relevant or to warrant urinary calcium monitoring for most patients.