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.
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.
Department of Pediatric Endocrinology, Children's Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, NY, USA. tponnapa@montefiore.org
Tulasi
T
Ponnapakkam
Ranjitha
R
Katikaneni
Hirofumi
H
Suda
Shigeru
S
Miyata
Osamu
O
Matsushita
Joshua
J
Sakon
Robert C
RC
Gensure
D045930:Anabolic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D015519:Bone Density / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000235:genetics*; D005260:Female; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D010281:Parathyroid Hormone / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000494:pharmacology
D045930:Anabolic Agents; D001426:Bacterial Proteins; D010281:Parathyroid Hormone; D011993:Recombinant Fusion Proteins; D003094:Collagen; D017364:Collagenases