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ZP2307, a novel, cyclic PTH(1-17) analog that augments bone mass in ovariectomized rats

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Harvard

Neerup, TSR, Stahlhut, M, Petersen, JS, Daugaard, JR, Jensen, J-EB, Peng, Z, Morko, J & Thorkildsen, C 2011, 'ZP2307, a novel, cyclic PTH(1-17) analog that augments bone mass in ovariectomized rats' Bone, vol. 48, no. 6, pp. 1319-27. https://doi.org/10.1016/j.bone.2011.02.019

APA

Neerup, T. S. R., Stahlhut, M., Petersen, J. S., Daugaard, J. R., Jensen, J-E. B., Peng, Z., ... Thorkildsen, C. (2011). ZP2307, a novel, cyclic PTH(1-17) analog that augments bone mass in ovariectomized rats. Bone, 48(6), 1319-27. https://doi.org/10.1016/j.bone.2011.02.019

CBE

Neerup TSR, Stahlhut M, Petersen JS, Daugaard JR, Jensen J-EB, Peng Z, Morko J, Thorkildsen C. 2011. ZP2307, a novel, cyclic PTH(1-17) analog that augments bone mass in ovariectomized rats. Bone. 48(6):1319-27. https://doi.org/10.1016/j.bone.2011.02.019

MLA

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Author

Neerup, Trine Skovlund Ryge ; Stahlhut, Martin ; Petersen, Jørgen S ; Daugaard, Jens Rejnhold ; Jensen, Jens-Erik B ; Peng, Zhiqi ; Morko, Jukka ; Thorkildsen, Christian. / ZP2307, a novel, cyclic PTH(1-17) analog that augments bone mass in ovariectomized rats. In: Bone. 2011 ; Vol. 48, No. 6. pp. 1319-27.

Bibtex

@article{fa2568c485ff404ab871a795810191cd,
title = "ZP2307, a novel, cyclic PTH(1-17) analog that augments bone mass in ovariectomized rats",
abstract = "Daily injections of human parathyroid hormone (1-34), hPTH(1-34), provide a highly effective treatment option for severe osteoporosis. However, PTH analogs shorter than 28 amino acids do not retain any bone augmenting potential. Here, we present ZP2307 ([Ac₅c¹, Aib³, Leu⁸, Gln¹⁰, Har¹¹, Ala¹², Trp¹⁴, Asp¹⁷]PTH(1-17)-NH₂), a novel, chemically modified and cyclized hPTH(1-17) analog, that augments bone mass in ovariectomized, osteopenic rats. Subcutaneous administration of this structurally constrained, K¹³-D¹⁷ side-chain-to-side-chain cyclized peptide reversed bone loss and increased bone mineral density (BMD) up to or above baseline levels in rat long bones and vertebrae. Highly significant effects of ZP2307 were achieved at doses of 40-320 nmol/kg. Micro-CT and histomorphometric analyses showed that ZP2307 improved quantitative and qualitative parameters of bone structure. Biomechanical testing of rat femora confirmed that ZP2307 dramatically increased bone strength. Over a broad maximally effective dose range (40-160 nmol/kg) ZP2307 did not increase serum concentrations of ionized free calcium above normal levels. Only at the highest dose (320 nmol/kg) ZP2307 induced hypercalcemic calcium levels in the ovariectomized rats. To our knowledge ZP2307 is the smallest PTH peptide analog known to exert augmentation of bone. Our findings suggest that ZP2307 has the potential to effectively augment bone mass over a broad dose range without a concomitant increase in the serum concentration of ionized free calcium above the normal range.",
keywords = "Absorptiometry, Photon, Animals, Bone Density, Bone Density Conservation Agents, Bone and Bones, Calcium, Cyclic AMP, Female, Organ Size, Ovariectomy, Parathyroid Hormone, Peptide Fragments, Rats, Rats, Inbred F344, Tomography, X-Ray Computed",
author = "Neerup, {Trine Skovlund Ryge} and Martin Stahlhut and Petersen, {J{\o}rgen S} and Daugaard, {Jens Rejnhold} and Jensen, {Jens-Erik B} and Zhiqi Peng and Jukka Morko and Christian Thorkildsen",
note = "Copyright {\circledC} 2011 Elsevier Inc. All rights reserved.",
year = "2011",
doi = "10.1016/j.bone.2011.02.019",
language = "English",
volume = "48",
pages = "1319--27",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc",
number = "6",

}

RIS

TY - JOUR

T1 - ZP2307, a novel, cyclic PTH(1-17) analog that augments bone mass in ovariectomized rats

AU - Neerup, Trine Skovlund Ryge

AU - Stahlhut, Martin

AU - Petersen, Jørgen S

AU - Daugaard, Jens Rejnhold

AU - Jensen, Jens-Erik B

AU - Peng, Zhiqi

AU - Morko, Jukka

AU - Thorkildsen, Christian

N1 - Copyright © 2011 Elsevier Inc. All rights reserved.

PY - 2011

Y1 - 2011

N2 - Daily injections of human parathyroid hormone (1-34), hPTH(1-34), provide a highly effective treatment option for severe osteoporosis. However, PTH analogs shorter than 28 amino acids do not retain any bone augmenting potential. Here, we present ZP2307 ([Ac₅c¹, Aib³, Leu⁸, Gln¹⁰, Har¹¹, Ala¹², Trp¹⁴, Asp¹⁷]PTH(1-17)-NH₂), a novel, chemically modified and cyclized hPTH(1-17) analog, that augments bone mass in ovariectomized, osteopenic rats. Subcutaneous administration of this structurally constrained, K¹³-D¹⁷ side-chain-to-side-chain cyclized peptide reversed bone loss and increased bone mineral density (BMD) up to or above baseline levels in rat long bones and vertebrae. Highly significant effects of ZP2307 were achieved at doses of 40-320 nmol/kg. Micro-CT and histomorphometric analyses showed that ZP2307 improved quantitative and qualitative parameters of bone structure. Biomechanical testing of rat femora confirmed that ZP2307 dramatically increased bone strength. Over a broad maximally effective dose range (40-160 nmol/kg) ZP2307 did not increase serum concentrations of ionized free calcium above normal levels. Only at the highest dose (320 nmol/kg) ZP2307 induced hypercalcemic calcium levels in the ovariectomized rats. To our knowledge ZP2307 is the smallest PTH peptide analog known to exert augmentation of bone. Our findings suggest that ZP2307 has the potential to effectively augment bone mass over a broad dose range without a concomitant increase in the serum concentration of ionized free calcium above the normal range.

AB - Daily injections of human parathyroid hormone (1-34), hPTH(1-34), provide a highly effective treatment option for severe osteoporosis. However, PTH analogs shorter than 28 amino acids do not retain any bone augmenting potential. Here, we present ZP2307 ([Ac₅c¹, Aib³, Leu⁸, Gln¹⁰, Har¹¹, Ala¹², Trp¹⁴, Asp¹⁷]PTH(1-17)-NH₂), a novel, chemically modified and cyclized hPTH(1-17) analog, that augments bone mass in ovariectomized, osteopenic rats. Subcutaneous administration of this structurally constrained, K¹³-D¹⁷ side-chain-to-side-chain cyclized peptide reversed bone loss and increased bone mineral density (BMD) up to or above baseline levels in rat long bones and vertebrae. Highly significant effects of ZP2307 were achieved at doses of 40-320 nmol/kg. Micro-CT and histomorphometric analyses showed that ZP2307 improved quantitative and qualitative parameters of bone structure. Biomechanical testing of rat femora confirmed that ZP2307 dramatically increased bone strength. Over a broad maximally effective dose range (40-160 nmol/kg) ZP2307 did not increase serum concentrations of ionized free calcium above normal levels. Only at the highest dose (320 nmol/kg) ZP2307 induced hypercalcemic calcium levels in the ovariectomized rats. To our knowledge ZP2307 is the smallest PTH peptide analog known to exert augmentation of bone. Our findings suggest that ZP2307 has the potential to effectively augment bone mass over a broad dose range without a concomitant increase in the serum concentration of ionized free calcium above the normal range.

KW - Absorptiometry, Photon

KW - Animals

KW - Bone Density

KW - Bone Density Conservation Agents

KW - Bone and Bones

KW - Calcium

KW - Cyclic AMP

KW - Female

KW - Organ Size

KW - Ovariectomy

KW - Parathyroid Hormone

KW - Peptide Fragments

KW - Rats

KW - Rats, Inbred F344

KW - Tomography, X-Ray Computed

U2 - 10.1016/j.bone.2011.02.019

DO - 10.1016/j.bone.2011.02.019

M3 - Journal article

VL - 48

SP - 1319

EP - 1327

JO - Bone

JF - Bone

SN - 8756-3282

IS - 6

ER -

ID: 34920861