A randomized, cross-over trial of once-daily versus twice-daily parathyroid hormone 1-34 in treatment of hypoparathyroidism

Abstract

Once-daily sc injection of PTH 1-34 can normalize mean serum and urine calcium levels in patients with hypoparathyroidism; however, once-daily PTH has diminishing effects on serum calcium after 12 h, such that serum calcium levels fall below the normal range in some patients. Once-daily PTH also causes a marked increase in bone turnover, with persistent increases in markers of bone formation and resorption. To test the hypothesis that a twice-daily PTH regimen can produce more physiological control than a once-daily regimen, we performed a randomized cross-over trial, lasting 28 weeks, in 17 adult subjects with hypoparathyroidism. Each 14-week study arm was divided into a 2-week inpatient dose-adjustment phase and a 12-week outpatient phase. The PTH dose (given sc once daily at 0900 h or twice daily with one dose at 0900 h and the other at 2100 h) was adjusted to maintain both serum and urine calcium within, or close to, the normal range. During the second half of the day (12-24 h), twice-daily PTH increased serum calcium and magnesium levels more effectively than once-daily PTH. In patients with calcium receptor mutations (CaR), once-daily PTH normalized urine calcium, provided that serum calcium was maintained at levels below normal range. However, twice-daily PTH treatment produced higher mean serum calcium in patients with CaR with no significant rise in urine calcium excretion, and with no significant differences in either serum or urine calcium levels between CaR and patients with acquired or idiopathic hypoparathyroidism. Thus, treatment with twice-daily PTH is the better regimen for patients with CaR to overcome their tendency to hypercalciuria while producing near-normal levels of serum calcium. The total daily PTH dose was markedly reduced with the twice-daily regimen (twice daily 46+/-52 vs. once daily 97+/-60 microg/day, P < 0.001). We conclude that a twice-daily PTH regimen provides effective treatment of hypoparathyroidism and reduces the variation in serum calcium levels at a lower total daily PTH dose.