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. (18th October 2013)

• Record Type: Journal Article
• Authors: 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‐Ocaña, Adolfo; Gundberg, Caren M; Cauley, Jane A; Stewart, Andrew F
• Is Part Of: Journal of bone and mineral research. Volume 28:Number 11(2013:Nov.)
• Page Start: 2266
• Page End: 2276
• Publication Date: 2013-10-18
• Subjects: Bones -- Metabolism -- Periodicals; Mineral metabolism -- Periodicals; 612.392
• DOI: 10.1002/jbmr.1978
• Languages: English
• ISSNs: 0884-0431

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="jbmr1978-sec-0001" sec-type="section"> <p>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 µg/day; PTHrP(1‐36) 600 µg/day; and PTH(1‐34) 20 µg/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)<sub>2</sub> vitamin D, and BMD. The increase in bone resorption (CTX) by PTH(1‐34) (92%) (<italic>p</italic> < 0.005) was greater than for PTHrP(1‐36) (30%) (<italic>p</italic> < 0.05). PTH(1‐34) also increased bone formation (PINP) (171%) (<italic>p</italic> < 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 (<italic>p</italic> < 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) (<italic>p</italic> < 0.05) at the TH and for PTHrP(1‐36) 400 (<italic>p</italic> < 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)<sub>2</sub>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. © 2013 American Society for Bone and Mineral Research. © 2013 American Society for Bone and Mineral Research.</p> </sec> </abstract>