Acute and subacute oral toxicity tests of sintered dicalcium pyrophosphate on ovariectomized rats for osteoporosis treatment

Kai Chiang Yang, Chen Chie Wang, Chang Chin Wu, Tsai Yi Hung, Hsiu Chi Chang, Hsiu Kang Chang, Feng Huei Lin

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7 Citations (Scopus)

Abstract

Sintered dicalcium pyrophosphate (SDCP) is a synthetic pyrophosphate analog that could be utilized in the treatment for osteoporosis. In this study, an ovariectomized rat model is used to evaluate the systematic toxicity of orally administered SDCP relative to its effects on bone mass. Ovariectomized Wistar rats were treated with experimental medication with different dosing strategies (0.5 mg/kg five days weekly, and 2.5 mg/kg once weekly) for once (acute oral toxicity test) and four weeks (subacute oral toxicity test) followed by recovery period. Clinical signs of toxicity, body weight, and food consumption of rats were recorded. Blood samples were collected for hematological and blood biochemical analyses. Rats were sacrificed for necropsy and major visceral organs were harvested for histological examination after the recovery period. Long bones of four limbs were harvested to evaluate the effects of SDCP on bone mass. Results showed that there was no change in clinical signs, body weight, food consumption, hematology, blood biochemistry, necropsy, and histological examination attributable to the oral administration with SDCP to rats during the dosing period and the recovery period. Analysis of bone ashes revealed that the ovariectomized rats ingested with 0.5 mg/kg SDCP five days weekly continually for four weeks increased bone mineral contents significantly. In the ovariectomized rats ingested with 2.5 mg/kg SDCP once weekly continually for four weeks, the bone mineral contents were increased to normal bone quality. This study indicates that the SDCP can increase bone mass in the ovariectomized rat with no deleterious effects.

Original languageEnglish
Pages (from-to)169-176
Number of pages8
JournalBiomedical Engineering - Applications, Basis and Communications
Volume22
Issue number3
DOIs
Publication statusPublished - Jun 2010
Externally publishedYes

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Keywords

  • Bisphosphonates
  • Oral administration
  • Osteoporosis
  • Pyrophosphate analog
  • Sintered dicalcium pyrophosphate

ASJC Scopus subject areas

  • Biophysics
  • Biomedical Engineering
  • Bioengineering

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