title: 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.
abstract: 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)2 vitamin D, and BMD. The increase in bone resorption (CTX) by PTH(1-34) (92%) (p < 0.005) was greater than for PTHrP(1-36) (30%) (p < 0.05). PTH(1-34) also increased bone formation (PINP) (171%) (p < 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 < 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 < 0.05) at the TH and for PTHrP(1-36) 400 (p < 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. © 2013 American Society for Bone and Mineral Research.
authors: Division of Endocrinology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors: Mara J
authors: MJ
authors: Horwitz
authors: Marilyn
authors: M
authors: Augustine
authors: Leila
authors: L
authors: Khan
authors: Leila
authors: L
authors: Kahn
authors: Emily
authors: E
authors: Martin
authors: Christine C
authors: CC
authors: Oakley
authors: Raquel M
authors: RM
authors: Carneiro
authors: Mary Beth
authors: MB
authors: Tedesco
authors: Angela
authors: A
authors: Laslavic
authors: Susan M
authors: SM
authors: Sereika
authors: Alessandro
authors: A
authors: Bisello
authors: Adolfo
authors: A
authors: Garcia-Ocaña
authors: Caren M
authors: CM
authors: Gundberg
authors: Jane A
authors: JA
authors: Cauley
authors: Andrew F
authors: AF
authors: Stewart
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism* / Q000652:urine; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D003710:Demography; D005260:Female; D006801:Humans; D008875:Middle Aged; D008903:Minerals / Q000097:blood / Q000652:urine; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D017698:Postmenopause / Q000097:blood / Q000187:drug effects* / Q000652:urine; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D015415:Biomarkers; D008903:Minerals; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D
keywords: ANABOLIC; BONE TURNOVER; DXA; OSTEOPOROSIS; PTH; PTHrP
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