Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Effects of metformin, rosiglitazone and insulin on bone metabolism in patients with type 2 diabetes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. P2X7Rs are involved in cell death, growth and cellular signaling in primary human osteoblasts

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Determinants of vitamin D status in a general population of Danish adults

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Abnormal bone collagen morphology and decreased bone strength in growth hormone-deficient rats

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Systemisk og lokal allergi over for humant insulin

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Trine Skovlund Ryge Neerup
  • Martin Stahlhut
  • Jørgen S Petersen
  • Jens Rejnhold Daugaard
  • Jens-Erik B Jensen
  • Zhiqi Peng
  • Jukka Morko
  • Christian Thorkildsen
Vis graf over relationer
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.
OriginalsprogEngelsk
TidsskriftBone
Vol/bind48
Udgave nummer6
Sider (fra-til)1319-27
Antal sider9
ISSN8756-3282
DOI
StatusUdgivet - 2011

ID: 34920861