Graves' Disease and Vertebral Fracture

Possible Pathogenic Link in Postmenopausal Women

Kai Takedani; Masakazu Notsu; Mika Yamauchi; Kiyoko Nawata; Toshitsugu Sugimoto; Keizo Kanasaki


Clin Endocrinol. 2020;93(2):204-211. 

In This Article

Abstract and Introduction


Background and Objective: Thyrotoxicosis is associated with accelerated bone turnover and increases the risk of fractures and osteoporosis. Graves' disease is the most common cause of hyperthyroidism. However, studies that examined risk factors associated with fragility fractures only in patients with Graves' disease are limited. Here, we investigated whether the risk of vertebral fracture (VF) of postmenopausal Graves' disease patients is high and tried to identify the risk factors for VF in that population.

Design and Methods: Forty-three postmenopausal women with Graves' disease were enrolled. Physical and biochemical indices, thyroid indices and bone mineral density (BMD) were measured, and lateral X-rays were obtained to evaluate VFs. Age- and sex-matched healthy individuals were enrolled as the control group (n = 86).

Results: The prevalence of VFs (35% vs 17%, P < .05), osteoporosis (63% vs 33%, P < .01) and severe osteoporosis (40% vs 17%, P < .01) was significantly higher in the Graves' disease group. Although there was no significant difference in either thyroid hormone levels or the positive ratio of thyroid antibodies, the prevalence of thyroid-stimulating antibody (TSAb) was significantly higher in Graves' disease patients with VF compared to without (100% vs 68%, P < .05). Multivariate logistic regression analyses adjusted for age identified Graves' disease as being associated with the presence of VFs (OR 2.72, 95% CI: 1.13–6.54, P < .05) in postmenopausal women.

Conclusions: Postmenopausal Graves' disease patients had high risks of VF and severe osteoporosis. TSAb could be involved as a risk factor for VF in postmenopausal Graves' disease.


Osteoporosis, a serious public health problem, is characterized by bone loss and continuous destruction of the bone microstructure. Osteoporotic fractures increase mortality, chronic pain, and the cost of care, and then decrease quality of life.[1–3] Especially in postmenopausal women, the number of osteoporotic fractures has been increasing each year in Japan.[4] Therefore, it is important to prevent osteoporotic fractures to extend healthy life expectancy.

Thyroid hormone regulates systemic metabolism, and it is also involved in bone metabolism.[5] Thyrotoxicosis is associated with accelerated bone turnover, and the risk of fractures and osteoporosis increases in patients with hyperthyroidism.[6] Graves' disease is the most common cause of hyperthyroidism.[7] The treatment approach for patients includes antithyroid drugs, radioiodine and thyroidectomy. Although some patients recur after initial treatment, all treatment options are similarly effective and bring good long-term outcomes.[8] A meta-analysis revealed that bone mineral density (BMD) was significantly decreased and fracture risk was increased in untreated hyperthyroidism; antithyroid therapies restored such reduced BMD levels to normal value.[6] On the other hand, previous studies demonstrated that a prior history of thyroid disease was independently associated with fracture as well.[9] Interestingly, women with a history of hyperthyroidism have shown to be experienced their first fracture at a younger age when compared to women without thyroid disease.[10] These reports suggest that both the appropriate evaluation and the optimal treatment of fractures are important to Graves' disease patients due to their long convalescence.

It is widely accepted that osteoporosis increases with menopause. An increased risk of osteoporosis has also been reported in postmenopausal Graves' disease patients.[11] The fracture risk has shown to be also increased in women older than 65 years of age who have low TSH levels.[12] This study has confirmed the relationships between fracture and hyperthyroidism due to not only Graves' disease, but other thyrotoxic states including thyroiditis, autonomous toxic goitre and pharmacological TSH suppression; there is no report that evaluates the risk of fragility fracture solely in postmenopausal Graves' disease patients. Therefore, the risk factors associated with fragility fracture in patients with Grave's disease have not been elucidated yet. Thus, the aim of this study was to clarify whether the risk of vertebral fracture (VF) is higher in postmenopausal Graves' disease patients than in healthy subjects. In addition, the risk factors for VF were also examined in the subjects.