Restoration of severely depleted femoral trabecular bone in ovariectomized rats by parathyroid hormone-(1-34).
It is commonly believed that the parathyroid hormone's (PTH's) main function in bone is to stimulate osteoclastic resorption. However, intermittent injections of small doses of PTH holoprotein, but more often its bioactive hPTH-(1-34) fragment, have been shown to stimulate bone growth in animals and humans through their ability to stimulate adenylyl cyclase and not their ability to independently activate a protein kinases-C stimulating mechanism. This anabolic action suggests that PTH might be an effective therapeutic for osteoporosis. If so, the hormone must be able to restore severely depleted trabecular bone, and the goal of this study was to find out if it can. To do this, we started a multiweek program of daily subcutaneous injections of 0.8 nmoles of hPTH-(1-34)/100 g body weight into rats at 4, 8, or 16 weeks after ovariectomy (OVX) and the increasingly severe selective loss of trabecular bone. These injections strongly stimulated femoral trabecular bone to grow and mineralize at the same rate regardless of how much of it had been lost before the injections were started. Thus, the progressively depleting trabecular bone in the femurs of OVX rats does not lose its anabolic responsiveness to PTH. This finding is another indication of the likelihood of small, adenylyl cyclase-stimulating PTH fragments being effective therapeutics for osteoporosis.
Whitfield
J F
JF
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario.
Morley
P
P
Ross
V
V
Isaacs
R J
RJ
Rixon
R H
RH
D000704:Analysis of Variance; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005269:Femur / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007279:Injections, Subcutaneous; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy; D010052:Ovariectomy / Q000009:adverse effects; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019379:Teriparatide
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D002118:Calcium