Abstract:

BACKGROUND: Levothyroxine can significantly improve the symptoms of subclinical hypothyroidism, and some studies have pointed out that levothyroxine can partially improve the abnormal bone metabolism of experimental rats, but the therapeutic effect of levothyroxine on subclinical hypothyroid osteoporosis is rarely studied.

OBJECTIVE: To observe the effects of aerobic exercise combined with levothyroxine and vitamin D3 on the symptoms of osteoporosis in subclinical hypothyroidism rats.

METHODS: Wistar rats were divided into blank control group, sham-operated group and model group. The thyroid function was measured to determine whether the model was successfully established. The model group rats were further divided into eight groups: non-treatment group, exercise group, L-thyroxine group, vitamin D3 group, exercise + levothyroxine group, exercise + vitamin D3 group, levothyroxine + vitamin D3 group and exercise + levothyroxine + vitamin D3 group, with another normal control group. At the 52th day after treatments, the bone resorption markers, β isomer of C-terminal telopeptide of type I collagen (β-CTX) and tartrate-resistant acid phosphatase-5b (TRACP-5b), and the bone formation markers, bone-specific alkaline phosphatase (BLAP), type I procollagen amino-terminal propeptide (PINP), and serum osteocalcin (BGP) were detected. Bone mineral density of the rat skull, spine, upper limb and lower limb was scanned. Serum calcium and phosphorus levels and cathepsin K level in the right femur were measured. Hematoxylin-eosin staining of the rat femoral head was performed.

RESULTS AND CONCLUSION: At the modeling stage, serum thyroid-stimulating hormone (TSH) level of rats in the model group was significantly higher than that in the sham-operated group and blank control group (P < 0.05). But there was no significant difference in serum T3 and T4 among the groups, indicating that the subclinical hypothyroidism rat model was successfully established. After treatment, compared with the rats without levothyroxine treatment, serum TSH levels in the rats of the levothyroxine group, the levothyroxine + vitamin D3 group, the exercise + levothyroxine group and the exercise + levothyroxine + vitamin D3 group were significantly decreased (P < 0.05), while the levels of T3 and T4 were not significantly changed. But the levels of β-CTx, TRACP-5b, BLAP, PINP, BGP and BMD in rats with levothyroxine treatment were significantly increased compared with those without levothyroxine treatment (P < 0.05). And the rats in the exercise + L-thyroxine + vitamin D3 group had the most significant improvement on the bone metabolism indexes and BMD (P < 0.05). Serum calcium and phosphorus levels of the rats in the levothyroxine + vitamin D3 group and the exercise + levothyroxine + vitamin D3 group were significantly higher than those in other groups with no vitamin D3 (P < 0.05). The rats in the levothyroxine group, the exercise + levothyroxine group, the levothyroxine + vitamin D3 and the exercise + levothyroxine group + vitamin D3 had the lower level of Cathepsin K level in femoral tissue than those in the other groups (P < 0.05). Moreover, the morphology of bone trabecular tissue was significantly improved in the rats with levothyroxine treatment than those with no levothyroxine treatment. To conclude, subclinical hypothyroidism can lead to osteoporosis in rats. Supplementation of levothyroxine is the most critical step of the treatments. Vitamin D3 can relieve osteoporosis by increasing serum calcium and phosphorus levels. Aerobic exercise can significantly enhance the improvement effect of levothyroxine and vitamin D3 on subclinical hypothyroidism osteoporosis. Therefore, comprehensive treatment of levothyroxine, vitamin D3 and aerobic exercise should be emphasized in the treatment of subclinical hypothyroidism osteoporosis.

Key words: osteoporosis, subclinical hypothyroidism, aerobic exercise, levothyroxine, vitamin D3