The effects of the aminobisphosphonate alendronate on thyroid hormone-induced osteopenia in rats.
Hyperthyroidism, either endogenous or iatrogenic, leads to increased bone turnover and osteopenia. This study was conducted to examine (1) whether thyroid hormone excess in rats causes bone changes similar to those seen in patients with hyperthyroidism, and (2) the effects of the aminobisphosphonate alendronate on the thyroid hormone-induced bone changes. Sprague-Dawley male rats, divided into four groups, received L-thyroxine (T4) 250 micrograms/kg/day (+T4) or vehicle (-T4) subcutaneously six times per week and alendronate 1.75 mg/kg (+ALN) or vehicle (-ALN) orally twice a week. Rats were sacrificed after 3 weeks of treatment, blood samples were analyzed for serum T4, triiodo-L-thyronine (T3), and osteocalcin, and the proximal tibiae were processed for histomorphometric analysis. Serum T4 and T3 levels measured 20-24 hours after the last injection were 2 to 2.5-fold higher in +T4 groups than in -T4 groups. Serum osteocalcin was significantly (P < 0.05) higher in +T4/-ALN group than in the other groups, which were not statistically different from each other. T4 treatment (+T4/-ALN) significantly decreased the amount of cancellous bone volume (-45%) and increased osteoid surface (+254%), osteoblast surface (+111%), and osteoclast surface (+176%) relative to control values. Alendronate increased the bone volume above control values in both T4-treated (+T4/+ALN) and untreated (-T4/+ALN) rats, and prevented the T4-induced increase in bone turnover in +T4/+ALN rats. It is concluded that (1) excess thyroid hormone induces cancellous bone loss associated with high bone turnover in the rat, and (2) this bone loss can be prevented by alendronate through the inhibition of osteoclastic activity.
Yamamoto
M
M
Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486.
Markatos
A
A
Seedor
J G
JG
Masarachia
P
P
Gentile
M
M
Rodan
G A
GA
Balena
R
R
D019386:Alendronate; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D004164:Diphosphonates / Q000494:pharmacology*; D004195:Disease Models, Animal; D006980:Hyperthyroidism / Q000139:chemically induced / Q000150:complications*; D008297:Male; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013974:Thyroxine / Q000494:pharmacology; D013977:Tibia / Q000187:drug effects / Q000473:pathology
D004164:Diphosphonates; D013974:Thyroxine; D019386:Alendronate