Bone-Targeting Parathyroid Hormone Analogues Outperform Unmodified PTH in the Anabolic Treatment of Osteoporosis in Rats

Yang Yang, Arash Panahifar, Yuchin Wu, Kathy Tang, Krishna H. Bhandari and Michael R. Doschak

Pharmaceutical Orthopaedic Research Lab, Faculty of Pharmacy and Pharmaceutical Sciences,
University of Alberta, Edmonton, AB, T6G 2E1, Canada

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Summary
Novel bone-targeting Parathyroid Hormonepolyethylene glycol-Bisphosphonate (PTH-PEG -BP) conjugates were synthesized, characterized and evaluated for bioactivity, bone affinity and anabolic efficacy in-vitro/vivo. Simple bisphosphonate (BP) moieties were conjugated to PTH using heterobifunctional PEG linkers in order to impart bone specificity for PTH after administration in a rat model of Osteoporosis, secondary to ovariectomy. Results for bone volume and new bone formation by Micro-CT, electron probe micro-analysis, and histological analysis showed significantly improved anabolic bone formation on treatment of osteoporotic rats using bone-targeting PTH-PEG-BP compared to currently marketed unmodified PTH.

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