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1.
PLoS One ; 12(4): e0175329, 2017.
Article in English | MEDLINE | ID: mdl-28394900

ABSTRACT

Teriparatide [human parathyroid hormone (1-34)], which exerts an anabolic effect on bone, is used for the treatment of osteoporosis in patients who are at a high risk for fracture. That the once-daily administration of teriparatide causes an increase in cortical porosity in animal models and clinical studies has been a matter of concern. However, it is not well documented that the frequency of administration and/or the total dose of teriparatide affect the cortical porosity. The present study developed 4 teriparatide regimens [20 µg/kg/day (D20), 40 µg/kg/day (D40), 140 µg/kg/week (W140) and 280 µg/kg/week (W280)] in the rabbit as a model animal with a well-developed Haversian system and osteons. The total weekly doses were equivalent in the low-dose groups (D20 and W140) and in the high-dose groups (D40 and W280). After the short-term (1 month) administration of TPDT, micro-CT, histomorphometry and three-dimensional second harmonic generation (3D-SHG) imaging to visualize the bone collagen demonstrated that daily regimens but not weekly regimens were associated with the significant development of cortical porosity and endosteal naïve bone formation by marrow fibrosis. We concomitantly monitored the pharmacokinetics of the plasma teriparatide levels as well as the temporal changes in markers of bone formation and resorption. The analyses in the present study suggested that the daily repeated administration of teriparatide causes more deleterious changes in the cortical microarchitecture than the less frequent administration of higher doses. The findings of the present study may have some implications for use of teriparatide in clinical treatment.


Subject(s)
Bone Density Conservation Agents/administration & dosage , Bone and Bones/drug effects , Osteogenesis/drug effects , Teriparatide/administration & dosage , Animals , Biomechanical Phenomena/drug effects , Bone Density Conservation Agents/adverse effects , Bone Density Conservation Agents/blood , Bone Resorption/chemically induced , Bone Resorption/metabolism , Bone Resorption/pathology , Bone and Bones/cytology , Bone and Bones/diagnostic imaging , Bone and Bones/metabolism , Collagen/drug effects , Collagen/metabolism , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Imaging, Three-Dimensional , Microscopy, Fluorescence , Microscopy, Interference , Models, Animal , Osteogenesis/physiology , Porosity/drug effects , Rabbits , Teriparatide/adverse effects , Teriparatide/blood , X-Ray Microtomography
2.
Bioorg Med Chem Lett ; 19(12): 3174-6, 2009 Jun 15.
Article in English | MEDLINE | ID: mdl-19447034
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