Stimulation of the growth of femoral trabecular bone in ovariectomized rats by the novel parathyroid hormone fragment, hPTH-(1-31)NH2 (Ostabolin).
The human parathyroid hormone, hPTH-(1-84), and its hPTH-(1-34) fragment are promising anabolic agents for treating osteoporosis because they can strongly stimulate the production of biomechanically effective cortical and trabecular bone in osteopenic ovariectomized (OVX) rats and trabecular bone in osteoporotic postmenopausal humans. The ideal PTH fragment for treating osteoporosis would be the smallest and functionally simplest fragment that activates only one signal mechanism and still strongly stimulates trabecular bone growth. A new PTH fragment, hPTH-(1-31)NH2, which only stimulates adenylyl cyclase instead of stimulating both adenylyl cyclase and phospholipase-C as do hPTH-(1-84) and hPTH-(1-34), is this minimum, high-potency anabolic fragment. hPTH-(1-31)NH2 (which we have named Ostabolin) can greatly thicken trabeculae and increase the dry weight and calcium content of trabecular bone in the distal femurs of osteopenic, young, sexually mature OVX Sprague-Dawley rats when injected subcutaneously each day for 6 weeks at doses between 0.4 and 1.6 nmole/100 g of body weight.
Whitfield
J F
JF
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario.
Morley
P
P
Willick
G E
GE
Ross
V
V
Barbier
J R
JR
Isaacs
R J
RJ
Ohannessian-Barry
L
L
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D002118:Calcium / Q000032:analysis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005269:Femur / Q000737:chemistry / Q000187:drug effects / Q000254:growth & development / Q000648:ultrastructure; D007279:Injections, Subcutaneous; D008855:Microscopy, Electron, Scanning; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010281:Parathyroid Hormone; D010446:Peptide Fragments; C102836:parathyroid hormone (1-31)amide, human; D002118:Calcium