Comparison of the ability of recombinant human parathyroid hormone, rhPTH-(1-84), and hPTH-(1-31)NH2 to stimulate femoral trabecular bone growth in ovariectomized rats.
A recombinant human parathyroid hormone, rhPTH-(1-84), which is currently in Phase II clinical trial, and hPTH-(1-31)NH2 (Ostabolin) are promising anabolic agents for treating osteoporosis because they can stimulate cortical and trabecular bone growth in osteopenic, ovariectomized (OVX) rats and in osteoporotic, postmenopausal women when injected subcutaneously and intermittently at low doses. We have now found that, despite their different sizes and signaling properties (rhPTH-(1-84) stimulates adenylyl cyclase and phospholipase C; hPTH-(1-31)NH2 only stimulates adenylyl cyclase), they are equally osteogenic in OVX rats. Thus daily subcutaneous injections of 0.6 nmol/100 g of body weight of rhPTH-(1-84) or hPTH-(1-31)NH2 into 3-month-old OVX rats for 6 weeks starting 2 weeks after OVX equally reduced the otherwise large OVX-triggered loss of femoral trabecular bone. Daily subcutaneous injections of 0. 4 or 0.8 nmol/100 g of body weight of the two agents for 6 weeks also equally increased the mean thickness of the remaining femoral trabeculae in 3-month-old and 1-year-old OVX rats to 20 to 80% above the value in normal animals when started 9 weeks after ovariectomy.
Whitfield
J F
JF
Institute for Biological Sciences, National Research Council of Canada, Building M-54, Montreal Road Campus, Ottawa, Ontario, Canada K1A 0R6.
Morley
P
P
Willick
G E
GE
Ross
V
V
MacLean
S
S
Barbier
J R
JR
Isaacs
R J
RJ
Ohannessian-Barry
L
L
D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects*; D005260:Female; D005269:Femur / Q000473:pathology*; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy* / Q000503:physiopathology; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000008:administration & dosage*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000008:administration & dosage*; D011506:Proteins / Q000008:administration & dosage*; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage; D015398:Signal Transduction / Q000187:drug effects
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D011994:Recombinant Proteins; C066077:parathyroid hormone-related protein (1-84); C102836:parathyroid hormone (1-31)amide, human