Abstract
Background: Several studies in adults and limited studies in youth have demonstrated decreased bone mineral density (BMD) and increased bone turnover in people with Graves’ disease (GD) with hyperthyroidism state. These negative impacts on bone loss can be reversed, in some extent, after normalizing of thyroid hormone. Low 25(OH)D was also prevalent in adults with GD that may worsen bone health. However, there has been no study evaluating 25(OH)D and its associations with BMD and markers of bone turnover in youth with GD. Objective: To evaluate BMD, bone turnover markers and 25(OH)D concentrations and the associations among these measures in youth with GD with varying thyroid status. Methods: Thirty participants with GD [age range 8-20 years; female 75%; mean BMI %tile 61±29 kg/m2, median Tanner stage 4 (3, 5)] were included in the study. Seventeen (57%) participants underwent radioactive iodine ablation. Twelve, seven and three participants had hyperthyroidism, euthyroidism/subclinical hypothyroidism and overt hypothyroidism, respectively. Participants were grouped according to free triiodothyronine [FT3] tertiles [low 2.3±0.8; medium 3.5±0.4; high 10.9±0.9 pg/ml]. Lumbar [L-BMD] and total body headless BMD [TBHL-BMD] were measured with Hologic Discovery A densitometry and compared with reference value (BMD z-score, BMDz). Morning serum concentrations of osteocalcin [OC], procollagen type 1 N-terminal propeptide [PINP], β-crosslaps [β-CTX] and 25(OH)D were also analyzed. Results: Mean L-BMDz and TBHL-BMDz in youth with GD were 0.256±1.064 and 0.011±0.898, respectively. Osteopenia was found in only one participant [L-BMDz -1.6 and TBLH-BMDz -1.2] who had thyrotoxicosis. L-BMDz (p=0.713) and TBLH-BMDz (p=0.91) were not significantly different between FT3 tertiles. There were no significant differences in OC [p=0.481], PINP [p=0.37], β-CTX [p=0.71] and 25(OH)D [p=0.91], adjusting for age, sex and BMI %tile, between FT3 tertiles. There were no significant associations among FT3, OC, PINP, β-CTX and BMDz. However, FT3 was negatively correlated with 25(OH)D [r=-0.574, p=0.032]. Participants with GD had mean 25(OH)D of 21.5±5.1 ng/ml. Twenty-nine out of 30 participants (97%) had 25(OH)D concentrations < 30 ng/ml. Of these, 11 participants (38%) had 25(OH)D < 20 ng/ml. Further, 25(OH)D was associated with L-BMDz [β (95%CI): 0.284 (0.091-0.477), p=0.013] and β-CTX [β (95%CI): 0.078 (0.020-0.136), p=0.011], independent of age, sex and BMI%tile. Conclusions: Vitamin D insufficiency/deficiency is prevalent in Thai youth with GD. Moreover, 25(OH)D concentrations, but not thyroid hormone, is independently associated with spine BMD and bone turnover. Therefore, evaluation and prompt treatment of vitamin D insufficiency/deficiency in pediatric GD are needed to prevent negative skeletal consequences.
Bone Mineral Density Increases with Vitamin D Repletion in Patients with Coexistent Vitamin D Insufficiency and Primary Hyperparathyroidism1
