Abstract
Thyroid hormone (TH) has a pivotal role in skeletal development, linear growth and maintenance of adult bone mass. Additionally, there are several studies which supported the direct effect of thyroid-stimulating hormone (TSH) on bone metabolism. As thyroid disease is one of the most common endocrine problems, the clinical impact of thyroid dysfunction on bone metabolism has been elucidated in various studies. Hyperthyroidism is associated with excessive loss of bone mass and an increased life-time risk for fractures. Adverse effects of hyperthyroidism in bone metabolism are distinct in postmenopausal women. Subclinical hyperthyroidism may also affect bone mineral density, however, its effect on fracture rate remains to be established. The effect of exogenous TH on bone tissue is somewhat controversial. Patients with hypothyroidism or differentiated thyroid carcinoma showing suppressed TSH caused by excessive TH replacement, especially postmenopausal women, appear to have lower bone mineral density and higher incidence of fractures than euthyroid subjects without exogenous TH. On the contrary, patients who are on exogenous TH with a normal range of TSH seem to have similar bone mineral density and fracture rates as euthyroid subjects. As most patients with differentiated thyroid carcinoma are taking exogenous thyroid hormone to suppress TSH, individual risks of both fracture and recurrence of carcinoma should be evaluated during the follow-up period of those patients. In general, in the management of thyroid disease, it should be taken into account that most thyroid dysfunction may result in reduced bone density and an increased fracture rate.
References
1. Vestergaard P, Rejnmark L, Weeke J, Mosekilde L. Fracture risk in patients treated for hyperthyroidism. Thyroid. 2000. 10(4):341–348.
2. Franklyn JA, Maisonneuve P, Sheppard MC, Betteridge J, Boyle P. Mortality after the treatment of hyperthyroidism with radioactive iodine. N Engl J Med. 1998. 338(11):712–718.
3. Mosekilde L, Eriksen EF, Charles P. Effects of thyroid hormones on bone and mineral metabolism. Endocrinol Metab Clin North Am. 1990. 19(1):35–63.
4. Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, et al. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med. 1995. 332(12):767–773.
5. Bayley TA, Harrison JE, McNeill KG, Mernagh JR. Effect of thyrotoxicosis and its treatment on bone mineral and muscle mass. J Clin Endocrinol Metab. 1980. 50(5):916–922.
6. Fraser SA, Anderson JB, Smith DA, Wilson GM. Osteoporosis and fractures following thyrotoxicosis. Lancet. 1971. 1(7707):981–983.
9. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000. 160(4):526–534.
10. Stall GM, Harris S, Sokoll LJ, Dawson-Hughes B. Accelerated bone loss in hypothyroid patients overtreated with L-thyroxine. Ann Intern Med. 1990. 113(4):265–269.
11. Uzzan B, Campos J, Cucherat M, Nony P, Boissel JP, Perret GY. Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis. J Clin Endocrinol Metab. 1996. 81(12):4278–4289.
12. Turner MR, Camacho X, Fischer HD, Austin PC, Anderson GM, Rochon PA, et al. Levothyroxine dose and risk of fractures in older adults: nested case-control study. BMJ. 2011. 342:d2238.
13. Abe E, Marians RC, Yu W, Wu XB, Ando T, Li Y, et al. TSH is a negative regulator of skeletal remodeling. Cell. 2003. 115(2):151–162.
14. Nagashima T, Murakami M, Onigata K, Morimura T, Nagashima K, Mori M, et al. Novel inactivating missense mutations in the thyrotropin receptor gene in Japanese children with resistance to thyrotropin. Thyroid. 2001. 11(6):551–559.
15. Mazziotti G, Sorvillo F, Piscopo M, Cioffi M, Pilla P, Biondi B, et al. Recombinant human TSH modulates in vivo C-telopeptides of type-1 collagen and bone alkaline phosphatase, but not osteoprotegerin production in postmenopausal women monitored for differentiated thyroid carcinoma. J Bone Miner Res. 2005. 20(3):480–486.
17. Kim DJ, Khang YH, Koh JM, Shong YK, Kim GS. Low normal TSH levels are associated with low bone mineral density in healthy postmenopausal women. Clin Endocrinol (Oxf). 2006. 64(1):86–90.
18. Bauer DC, Ettinger B, Nevitt MC, Stone KL. Risk for fracture in women with low serum levels of thyroid-stimulating hormone. Ann Intern Med. 2001. 134(7):561–568.
19. Mazziotti G, Porcelli T, Patelli I, Vescovi PP, Giustina A. Serum TSH values and risk of vertebral fractures in euthyroid post-menopausal women with low bone mineral density. Bone. 2010. 46(3):747–751.