TY - JOUR
T1 - A single injection of the anabolic bone agent, parathyroid hormone-collagen binding domain (PTH-CBD), results in sustained increases in bone mineral density for up to 12 months in normal female mice
AU - Ponnapakkam, Tulasi
AU - Katikaneni, Ranjitha
AU - Suda, Hirofumi
AU - Miyata, Shigeru
AU - Matsushita, Osamu
AU - Sakon, Joshua
AU - Gensure, Robert C.
N1 - Funding Information:
We thank the Ochsner Clinic Foundation for providing support for these studies. Supported in part by the National Institutes of Health Center for Protein Structure and Function grants NCRR COBRE 1 P20RR15569 and INBRE P20RR16460; AR Biosciences Institute (ABI); and a grant-in-aid for scientific research from the Japan Society for the Promotion of Science and Kagawa University Project Research Fund, 2005–2006. We thank Dr. Alan Burshell, section head, Department of Endocrinology, Ochsner Clinic Foundation, New Orleans, LA, for his support and advice.
PY - 2012/9
Y1 - 2012/9
N2 - 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 μg/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.
AB - 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 μg/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.
KW - Animal models
KW - Bone density technology
KW - DXA
KW - Osteoporosis therapy
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U2 - 10.1007/s00223-012-9626-1
DO - 10.1007/s00223-012-9626-1
M3 - Article
C2 - 22806683
AN - SCOPUS:84866017861
SN - 0171-967X
VL - 91
SP - 196
EP - 203
JO - Calcified Tissue International
JF - Calcified Tissue International
IS - 3
ER -