Excessive L-thyroxine therapy decreases femoral bone mineral densities in the male rat: effect of hypogonadism and calcitonin.
Excess thyroid hormone decreases bone mineral density (BMD), a potential problem in managing patients with differentiated thyroid carcinoma and nontoxic goiter who require lifelong TSH-suppressive doses of thyroid hormone. We studied the effect of thyroid hormone excess on vertebral and femoral BMD and the role of hypogonadism in modulating this effect in a rat model. The potential role of calcitonin (CT) in preventing thyroid hormone-associated bone loss was also investigated. A total of 40 male Sprague-Dawley rats were divided into four groups. Groups 1 and 2 were orchidectomized (ORX); groups 3 and 4 were sham operated (SO). Groups 1 and 3 received 20 micrograms intraperitoneal L-thyroxine (L-T4) per 100 g body weight daily for 3 weeks; groups 2 and 4 received vehicle IP. Another 40 rats were divided into four groups. Groups 1 and 2 received L-T4, and groups 1 and 3 received CT, 2.5 U per 100 g body weight, subcutaneously (SC) daily for 3 weeks. BMD of the L4 and 5 and the right femur were measured by dual-energy x-ray absorptiometry at baseline and at the end of the study. Orchidectomy decreased femoral (P < 0.05) but not lumbar BMD. The administration of excess L-T4 decreased femoral (cortical) BMD in both SO (P < 0.05) and ORX rats (P < 0.05) without affecting lumbar (trabecular) BMD. CT increased lumbar BMD in both vehicle (P < 0.001) and L-T4-treated rats (P < 0.001). However, CT did not affect femoral BMD in vehicle-treated rats and did not prevent the L-T4-induced femoral bone loss.(ABSTRACT TRUNCATED AT 250 WORDS)
Ongphiphadhanakul
B
B
Division of Endocrinology and Metabolism, University of Massachusetts Medical School, Worcester.
Alex
S
S
Braverman
L E
LE
Baran
D T
DT
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D002116:Calcitonin / Q000494:pharmacology*; D005269:Femur; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D007006:Hypogonadism / Q000503:physiopathology*; D008159:Lumbar Vertebrae; D008297:Male; D009919:Orchiectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013974:Thyroxine / Q000633:toxicity*
D012739:Gonadal Steroid Hormones; D002116:Calcitonin; D013974:Thyroxine