Lumbar vertebral density and mechanical properties in aged ovariectomized rats treated with estrogen and norethindrone or norgestimate.
OBJECTIVE
This study was designed to investigate the effects of estrogen alone or combined with two different progestins, norethindrone or norgestimate, on bone density and compressive mechanical properties in an aged rat model.


METHODS
Twenty 11-month-old female Sprague-Dawley rats were sham operated (intact control) and 80 wee ovariectomized. Three groups of 20 ovariectomized rats were implanted with Silastic silicon rubber (Dow Corning, Midland, Mich.) capsules containing 5% estradiol (wt/wt) in cholesterol. All rats in the intact control (group 1) and the ovariectomized (group 2) and the first of the ovariectomized plus estrogen (group 3) groups were injected subcutaneously daily for 6 months with corn oil (vehicle). Two other groups of rats with estrogen capsules received daily injections of norethindrone (3 micrograms/rat/day) or norgestimate (1.5 micrograms/rat/day) in corn oil for 3 days out of every 6 days (interrupted progestin). The effects of these various treatments on bone mineral content and bone mineral density in the vertebrae were measured by dual energy x-ray absorptiometry. The L4 vertebral bodies were also tested to failure in compression.


RESULTS
The ovariectomized rats receiving corn oil alone had the lowest bone mineral density compared with intact controls. Estrogen treatment alone resulted in a lower bone mineral density than in the intact controls. In contrast, both interrupted progestin regimens resulted in vertebral bone mass index at the same level as the intact controls. Compression tests revealed that ovariectomized controls also had the lowest modulus of elasticity of all groups. However, unlike bone mineral density, estrogen alone resulted in mechanical properties similar to intact controls, whereas the vertebrae in both interrupted progestin groups had variable mechanical properties compared with the ovariectomized and intact control groups.


CONCLUSIONS
We conclude that in this experimental model hormone replacement therapy with estrogen and an androgenic (norethindrone) or nonadrogenic (norgestimate) progestin result in similar bone mineral density and mechanical properties. In addition, both interrupted progestin regimens had a better effect than estrogen alone on vertebral bone density.
Vanin
C M
CM
Division of Reproductive Sciences, Toronto Hospital Research Institute, Ontario, Canada.
MacLusky
N J
NJ
Chachra
D
D
Kasra
M
M
Grynpas
M D
MD
Casper
R F
RF
D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000502:physiology*; D009640:Norethindrone / Q000008:administration & dosage / Q000494:pharmacology*; D009644:Norgestrel / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012826:Silicone Elastomers
D004343:Drug Implants; D012826:Silicone Elastomers; D013196:Dihydrotestosterone; D009644:Norgestrel; D004958:Estradiol; C017576:norgestimate; D009640:Norethindrone