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KMID : 0352519970340010060
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Korea Univercity Medical Journal
1997 Volume.34 No. 1 p.60 ~ p.72
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An Experimental Study about the Effects of Parathyroid Hormone, Estrogen, and Calcitonin on Bone Mass and Vertebral Strength in Oophorectomized Rats
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Abstract
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Osteoporosis can be therapeutically approached in two different ways : by use of either antiresorptive agents (e.g. estrogen and calcitonin) or anabolic agents (e.g. parathyroid hormone, PTH). Estrogen and calcitonin as antiresorptive agent have
shown
to decrease bone resorption and increase bone density slightly in osteoporotic women. PTH has long been noted for its osteolytic effect on skeleton. Some of the recent works suggest that PTH may promote bone formation as well to be classified as
anabolic agent. Estrogen can not reverse advanced osteoporosis because it dosen't add bone where it is already defective. The combination therapy of PTH with antiresorptive agents would be an attractive option for treatment.
The author conducted an experimental study to elucidate the effect of combination therapy of antiresorptive agents (estrogen, calcitonin) with anabolic agent-human parathyroid hormone(1-34) (hPTH, 1-34) on bone mass by measuring bone mineral
density of
the proximal tibia, biomechanical competence of the 5th lumbar vertebra and osteocalcin value in serum.
Sixty five 3-month-old white female Sprague Dawley rats weighing 200-250gm were chosen. They were oophorectomized (OVX) bilaterally or sham-operated. The oophorectomized rat were randomized into 6 groups excluding sham operated group (Group 2) :
Group 1
(control, n=10), bilateral OVX plus saline (0.1ml) ; Group 2 (n=9), sham operated ; Group 3 (n=10), OVX plus 20ug/kg of estrogen (17-β estradiol); Group 4 (n=8), OVX plus 10ug/kg of calcitonin; Group 5 (n=10), OVX plus 80ug/kg of PTH ; Group 6
(n=9),
OVX plus 20ug/kg of estrogen and 80ug/kg of PTH ; and Group 7 (n=9) OVX plus 10ug/kg of calcitonin and 80㎍/kg of PTH.
The 5th lumbar vertebra was tested along the cranio-caudal axis in a universal testing machine at the normal deformation rate of 2 mm/min. at biomechanical testing.
Bone mineral density of the proximal tibia was measured by dual energy x-ray absorptiometry. The osteocalcin value of serum was measured by EIA kit.
All rats were untreated for the first 8 weeks after surgery to await development of moderate osteopenia and treated for the following four weeks according to protocols of hormone therapy. Differences between each group were evaluated with the
Kruskal-Wallis test.
@ES The results were as follows :
@EN 1. Bone mineral density of the proximal tibia were 0.0655 ±0.0095 mg/㎤for Group 3 ; 0.0686 ±0.0112 mg/㎤ for Group 4 ; 0.0845 ±0.0093 mg/㎤ for Group 5 ; 0.0788 ±0.0117 mg/㎤ for Group 6 ; 0.0792 ±0.0111 mg/㎤ for Group 7 respectively.
The
higher value of the bone mineral density of the proximal tibia were measured in Group 5, Group 3, Group 7, and Group 6 in orders except sham operated group (Group 2) and it was shown to have higher value in all groups than control group (group 1)
(p<0.05).
2. Maximum stress value of the 5th lumbar vertebra were 25.11 ±5.692 MP3 for Group 1 ; 30.03 ±6.237 MP3 for Group 2 ; 28.71 ±1.273 MP3 for Group 3 ; 23.81 ±6.364 MP3 for Group 4 ; 29.83 ±0.424 MP3 for Group 5 ; 26.17 ±4.243 MP3 for Group 6
;
26.07 ±6.223 MP3 for Group 7 respectively. These show the higher value in Group 5, Group 3, Group 6, and Group 7 in orders except sham operated group (Group 2) and it was shown to have higher value in all groups except Group 4 than Group 1
(p<0.05).
3. The osteocalcin value of serum were 1.04 ±0.589 ng/ml for Group 1 ; 1.18 ±0.646 ng/ml for Group 2 ; 1.35 ±0.331 ng/ml for Group 3 : 1.29 ±0.538 ng/ml for Group 4 ; 1.13 ±0.389 ng/ml for Group 5 ; 0.89 ±0.429 ng/ml for Group 6 ; 0.99
±0.379
ng/ml for Group 7 respectively. There was no significant difference among the groups.
In conclusion, above results made it clear that estrogen and PTH are effective agents for treatment of postmenopausal osteoporosis and suggested that PTH can be used in combination with antiresorptive agents.
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KEYWORD
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