Risk of Fractures in Thyroid Cancer Patients With Postoperative Hypoparathyroidism: A Nationwide Cohort Study in Korea

Abstract

Postoperative hypoparathyroidism (PO‐hypoPT) is an uncommon complication of total thyroidectomy in thyroid cancer patients. Although long‐term hypoPT causes characteristic changes in bone metabolism, the risk of fractures in hypoPT remains inconclusive. We investigated the risk of fractures in Korean thyroid cancer patients with PO‐hypoPT. This was a retrospective cohort study using data from the Korea Central Cancer Registry and Korean National Health Insurance Service. We analyzed 115,821 thyroid cancer patients aged ≥18 years, who underwent total thyroidectomy between 2008 and 2016. The risk of any fractures, including vertebral, hip, humerus, and wrist fractures, according to parathyroid function after total thyroidectomy, was analyzed using the multivariable Cox proportional hazard model. The PO‐hypoPT and preserved parathyroid function groups included 8789 (7.6%) and 107,032 (92.4%) patients, respectively. Over a mean follow‐up duration of 4.8 years, 159 (1.8%) and 2390 (2.2%) fractures occurred in the PO‐hypoPT and preserved parathyroid function groups, respectively. The risk of any fractures was significantly lower in the PO‐hypoPT group than in the preserved parathyroid function group (hazard ratio [HR] = 0.83; 95% confidence interval [CI] 0.70–0.98; p = 0.037) after adjusting for confounders. Regarding the fracture site, only the risk of vertebral fractures was significantly lower in the PO‐hypoPT group compared with the preserved parathyroid function group (HR = 0.67; 95% CI 0.47–0.96; p = 0.028) after adjusting for confounders. Subgroup analyses showed that bone mineral density measurements and calcium supplementation interacted with the relationship between PO‐hypoPT and the risk of any fractures (p for interactions = 0.010 and 0.017, respectively). PO‐hypoPT was associated with a lower risk of fractures in thyroid cancer patients, especially at the vertebra. The relatively low bone turnover caused by PO‐hypoPT and appropriate management for PO‐hypoPT with active vitamin D and calcium may prevent the deterioration of skeletal health in thyroid cancer patients who can easily be exposed to long‐term overtreatment with levothyroxine. © 2023 American Society for Bone and Mineral Research (ASBMR).

Hypoparathyroidism update

“…Hazard ratio was 0.83 (CI = 0.70–0.98; P = 0.037) after adjusting for confounders of BMD measurement and prescribed osteoporosis medication. Analysis of fracture site noted only vertebral fracture incidence was lower in the hypoPTH group (hazard ratio = 0.67; 95% CI 0.47–0.96; P = 0.028) [36 ▪▪ ]. No difference was noted for wrist, hip and humerus fracture.…”

Review on the protective activity of osthole against the pathogenesis of osteoporosis

“…Hyperthyroidism induced by thyroid-stimulating hormone-suppressive therapy in patients with thyroid cancer contributes to OP development and the risk of fractures ( Hong and Kang, 2023 ). Chronic PTH deficiency may induce bone microstructure alterations, bone remodeling imbalance, and increased fragility fractures ( Ahn et al, 2023 ). In addition, continuous exposure to high levels of PTH reduces BMD and increases the risks of fragility fractures by increasing bone resorption ( Silva and Bilezikian, 2021 ).…”

Advances in assessment and treatment of bone, mineral and parathyroid disorders

“…164–169), hypoPTH is associated with reduced bone turnover and increased bone density (BMD). Fracture outcomes in hypoPTH patients were unclear, but a recent large study of patients post total thyroidectomy may point to a protective effect of hypoparathyroidism on fracture [15]. Maintenance of calcium balance with conventional therapy using calcium and active vitamin D analogue without under- or over-replacement is a delicate task and often impossible in the brittle hypoPTH patients.…”