A Comparison of Parathyroid Hormone-Related Protein (1-36) and Parathyroid Hormone (1-34) on Markers of Bone Turnover and Bone Density in Postmenopausal Women: The PrOP Study

作者：Horwitz Mara J^*; Augustine Marilyn; Kahn Leila; Martin Emily; Oakley Christine C; Carneiro Raquel M; Tedesco Mary Beth; Laslavic Angela; Sereika Susan M; Bisello Alessandro; Garcia Ocana Adolfo; Gundberg Caren M; Cauley Jane A; Stewart Andrew F

来源：Journal of Bone and Mineral Research, 2013, 28(11): 2266-2276.

DOI：10.1002/jbmr.1978

• OSTEOPOROSIS
• PTH
• PTHrP
• ANABOLIC
• BONE TURNOVER
• DXA

Parathyroid hormone-related protein (PTHrP)(1-36) increases lumbar spine (LS) bone mineral density (BMD), acting as an anabolic agent when injected intermittently, but it has not been directly compared with parathyroid hormone (PTH)(1-34). We performed a 3-month randomized, prospective study in 105 postmenopausal women with low bone density or osteoporosis, comparing daily subcutaneous injections of PTHrP(1-36) to PTH(1-34). Thirty-five women were randomized to each of three groups: PTHrP(1-36) 400 mu g/day; PTHrP(1-36) 600 mu g/day; and PTH(1-34) 20 mu g/day. The primary outcome measures were changes in amino-terminal telopeptides of procollagen 1 (PINP) and carboxy-terminal telopeptides of collagen 1 (CTX). Secondary measures included safety parameters, 1,25(OH)(2) vitamin D, and BMD. The increase in bone resorption (CTX) by PTH(1-34) (92%) (p%26lt;0.005) was greater than for PTHrP(1-36) (30%) (p%26lt;0.05). PTH(1-34) also increased bone formation (PINP) (171%) (p%26lt;0.0005) more than either dose of PTHrP(1-36) (46% and 87%). The increase in PINP was earlier (day 15) and greater than the increase in CTX for all three groups. LS BMD increased equivalently in each group (p%26lt;0.05 for all). Total hip (TH) and femoral neck (FN) BMD increased equivalently in each group but were only significant for the two doses of PTHrP(1-36) (p%26lt;0.05) at the TH and for PTHrP(1-36) 400 (p%26lt;0.05) at the FN. PTHrP(1-36) 400 induced mild, transient (day 15) hypercalcemia. PTHrP(1-36) 600 required a dose reduction for hypercalcemia in three subjects. PTH(1-34) was not associated with hypercalcemia. Each peptide induced a marked biphasic increase in 1,25(OH)(2)D. Adverse events (AE) were similar among the three groups. This study demonstrates that PTHrP(1-36) and PTH(1-34) cause similar increases in LS BMD. PTHrP(1-36) also increased hip BMD. PTH(1-34) induced greater changes in bone turnover than PTHrP(1-36). PTHrP(1-36) was associated with mild transient hypercalcemia. Longer-term studies using lower doses of PTHrP(1-36) are needed to define both the optimal dose and full clinical benefits of PTHrP.

• 出版日期2013-11