Journal
CALCIFIED TISSUE INTERNATIONAL
Volume 91, Issue 3, Pages 196-203Publisher
SPRINGER
DOI: 10.1007/s00223-012-9626-1
Keywords
Animal models; Bone density technology; DXA; Osteoporosis therapy
Categories
Funding
- Ochsner Clinic Foundation
- National Institutes of Health Center for Protein Structure and Function [NCRR COBRE 1 P20RR15569, INBRE P20RR16460]
- AR Biosciences Institute (ABI)
- Japan Society for the Promotion of Science
- Kagawa University
- Grants-in-Aid for Scientific Research [23590516, 24590538] Funding Source: KAKEN
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Parathyroid hormone (PTH) is the most effective osteoporosis treatment, but it is only effective if administered by daily injections. We fused PTH(1-33) to a collagen binding domain (PTH-CBD) to extend its activity, and have shown an anabolic bone effect with monthly dosing. We tested the duration of action of this compound with different routes of administration. Normal young C57BL/6J mice received a single intraperitoneal injection of PTH-CBD (320 mu g/kg). PTH-CBD treated mice showed a 22.2 % increase in bone mineral density (BMD) at 6 months and 12.8 % increase at 12 months. When administered by subcutaneous injection, PTH-CBD again caused increases in BMD, 15.2 % at 6 months and 14.3 % at 12 months. Radiolabeled PTH-CBD was concentrated in bone and skin after either route of administration. We further investigated skin effects of PTH-CBD, and histological analysis revealed an apparent increase in anagen VI hair follicles. A single dose of PTH-CBD caused sustained increases in BMD by > 10 % for 1 year in normal mice, regardless of the route of administration, thus showing promise as a potential osteoporosis therapy.
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