Differences in bone turnover and skeletal response to thyroid hormone treatment between estrogen-depleted and repleted rats

This study was undertaken to compare the effect of supraphysiological doses of thyroxine (T4) on bone metabolism in SHAM and OVX young adult rats. Fem ale Sprague Dawley rats (220 +/- 2 g, approx. 5 months of age) were divided into four groups of eight animals each. The animals were intraperitoneally injected 6 days per week with vehicle (Vh): 0.001 N NaOH/0.9% NaCl (SHAM+V h and OVX+Vh) or 250 mu g of thyroxine/kg/day (SHAM+T4 and OVX+T4) during a 5-week period. Serum T4 and osteocalcin (BGP), urinary pyridinolines (Pyr) , and creatinine (creat) were determined. At the beginning and at end of th e experiment, skeletal bone mineral content (BMC), bone mineral density (BM D), and area (A) of the total skeleton, femur, spine, and whole tibia, as w ell as proximal, middle, and distal areas of the tibia were assessed by dua l X-ray absorptiometry (DXA) in an ultra-high-resolution mode. T4 treatment of the SHAM rats did not induce significant changes in BGP level or Pyr/cr eat excretion compared with the SHAM+Vh control group. However, these two b iochemical bone markers significantly increased due to T4 treatment in OVX rats compared with both OVX+Vh and SHAM+T4 groups (P < 0.05 and P < 0.001, respectively). The OVX+T4 group had a significantly lower Delta BMD than SH AM+T4 rats in all studied regions (P < 0.05) except for the middle tibia re gion. OVX+T4 groups presented a significantly lower Delta BMC and Delta A c ompared with SHAM+T4 animals (P < 0.001). OVX+T4 rats significantly impaire d the Delta BMD in the femur (P < 0.01), spine (P < 0.05), whole (P < 0.05) and middle (P < 0.05) tibia whereas T4 treatment of SHAM rats only affecte d, significantly, the whole (P < 0.05) and the proximal tibia region (P < 0 .01). T4 treatment affects bone growth in young adult rats. The effect is s ignificantly greater in the estrogen-depleted than in the estrogen-repleted state. The bone site most adversely affected by T4 treatment depends on th e estrogen status. The proximal tibia (principally trabecular bone) was the most affected area in estrogen-repleted rats. Conversely, in OVX rats, the middle tibia (principally cortical bone) presented the greatest decrease i n bone density.