Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 196-203 |
| Number of pages | 8 |
| Journal | Calcified Tissue International |
| Volume | 91 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 2012 |
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Keywords
- Animal models
- Bone density technology
- DXA
- Osteoporosis therapy
ASJC Scopus subject areas
- Orthopedics and Sports Medicine
- Endocrinology, Diabetes and Metabolism
- Endocrinology
Cite this
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. / Ponnapakkam, Tulasi; Katikaneni, Ranjitha; Suda, Hirofumi; Miyata, Shigeru; Matsushita, Osamu; Sakon, Joshua; Gensure, Robert C.
In: Calcified Tissue International, Vol. 91, No. 3, 09.2012, p. 196-203.Research output: Contribution to journal › Article
}
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.
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
UR - http://www.scopus.com/inward/record.url?scp=84866017861&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866017861&partnerID=8YFLogxK
U2 - 10.1007/s00223-012-9626-1
DO - 10.1007/s00223-012-9626-1
M3 - Article
VL - 91
SP - 196
EP - 203
JO - Calcified Tissue International
JF - Calcified Tissue International
SN - 0171-967X
IS - 3
ER -