Prolonged low-dose infusion of human parathyroid hormone does not increase femoral cancellous bone volume in ovariectomized rats.
OBJECTIVE
Daily injections of human parathyroid hormone (hPTH) increase bone volume in various animal species and in osteoporotic women. For hPTH to be widely accepted as an anabolic therapy for treating postmenopausal osteoporosis alternative delivery options need to be explored to replace the need for daily patient subcutaneous self-injection. Among these are inhalation, oral delivery and the use of programmable implanted minipumps to deliver the peptide. While infusion of high doses of PTH causes bone loss and hypercalcemia, no studies have assessed the effects of prolonged infusion of low doses of PTH on bone growth.


METHODS
[Leu(27)]-cyclo(Glu(22)-Lys(26))-hPTH-(1--31)NH(2) was delivered by Alzet minipumps to ovariectomized rats for 6 weeks after which histomorphometric indices (cancellous bone volume, trabecular thickness, mean trabecular number) of bone formation were measured in distal femurs.


RESULTS
Infusing low doses (0.05 and 0.1 nmole/100g body weight/day) of the hPTH analog, [Leu(27)]-cyclo(Glu(22)-Lys(26))-hPTH-(1--31)NH(2), for 6 weeks does not prevent the ovariectomy-induced loss of rat femoral cancellous bone volume, trabecular thickness or trabecular number.


CONCLUSIONS
These results support the absolute requirement of daily injections for the osteogenic action of hPTH on bone.
Institute for Biological Sciences, National Research Council of Canada, Building M-54, Montreal Road Campus, Ottawa, Ontario, Canada K1A 0R6.
P
P
Morley
J F
JF
Whitfield
G E
GE
Willick
V
V
Ross
S
S
MacLean
R J
RJ
Isaacs
E
E
Mendoza
J R
JR
Barbier
D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000187:drug effects*; D005260:Female; D005269:Femur; D006801:Humans; D010024:Osteoporosis / Q000517:prevention & control*; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000008:administration & dosage*; D010446:Peptide Fragments / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010281:Parathyroid Hormone; D010446:Peptide Fragments; C116052:parathyroid hormone (1-31)-NH2, leucyl(27)-cyclo(glutamyl(22)-lysyl(26))-