Department of Family Medicine & Supportive Care Center, Samsung Medical Center, Seoul, Republic of Korea.
Lunit Inc, Seoul, Republic of Korea.
J Bone Miner Res. 2018 Jun;33(6):1037-1043. doi: 10.1002/jbmr.3407. Epub 2018 Mar 24.
Long-term administration of supraphysiologic dosages of levothyroxine can have detrimental effect on the bone. We aimed to investigate fracture incidence among post-thyroidectomy thyroid cancer patients compared with a matched comparison group, and explore the association between levothyroxine dosage and fracture risk. From the Korean National Health Insurance database, virtually all thyroid cancer patients who received thyroidectomy in Korea from January 1, 2004 to December 31, 2012 were included. Matched subjects were selected by 1:1 propensity score matching. Cox proportional hazards regression analysis was used to determine relative risk of osteoporotic fracture. Of 185,956 thyroid cancer patients identified, fracture events were observed in 1096 subjects (0.56%) over a mean 4.35 years of follow-up. Compared to the matched comparison group, thyroid cancer patients had no elevated risk of osteoporotic fracture (hazard ratio [HR] 1.03; 95% confidence interval [CI], 0.94 to 1.12); however, the highest dosage group (≥170 μg/day) showed significantly higher risk (HR 1.25; 95% CI, 1.07 to 1.45), while the second quartile dosage group (115-144 μg/day) showed lower risk (HR 0.71; 95% CI, 0.59 to 0.84) compared to a matched comparison group. When the second quartile dosage group was considered as reference, increased fracture risk was observed in those who took either lower (first quartile: adjusted HR 1.31; 95% CI, 1.08 to 1.59) or higher dosage of levothyroxine (third quartile: adjusted HR 1.50; 95% CI, 1.26 to 1.79; fourth quartile: adjusted HR 1.79; 95% CI, 1.51 to 2.13). Thyroid cancer patients were more likely to be treated with osteoporosis medication (HR 1.22; 95% CI, 1.18 to 1.26) than the matched comparison group. Both high and low dosage of levothyroxine treatment was associated with a higher risk for fractures in a J-shaped dose-dependent manner in post-thyroidectomy patients. Future studies are needed to determine how to optimize thyroid-stimulating hormone (TSH) suppression and how to screen and manage fracture risk. © 2018 American Society for Bone and Mineral Research.
长期服用生理剂量以上的左旋甲状腺素可能对骨骼产生不良影响。我们旨在调查甲状腺癌患者术后骨折的发生率，并探讨左旋甲状腺素剂量与骨折风险之间的关系。从韩国国家健康保险数据库中，我们纳入了 2004 年 1 月 1 日至 2012 年 12 月 31 日期间在韩国接受甲状腺切除术的所有甲状腺癌患者。通过 1:1 倾向评分匹配选择匹配的对照组。使用 Cox 比例风险回归分析确定骨质疏松性骨折的相对风险。在 185956 例甲状腺癌患者中，平均随访 4.35 年后，1096 例（0.56%）发生骨折事件。与匹配的对照组相比，甲状腺癌患者发生骨质疏松性骨折的风险并未增加（风险比[HR]1.03；95%置信区间[CI]，0.94 至 1.12）；然而，最高剂量组（≥170μg/天）的风险显著增加（HR 1.25；95%CI，1.07 至 1.45），而第二四分位剂量组（115-144μg/天）的风险较低（HR 0.71；95%CI，0.59 至 0.84）与匹配的对照组相比。当以第二四分位剂量组为参考时，与服用较低（第一四分位：调整后的 HR 1.31；95%CI，1.08 至 1.59）或较高剂量的左旋甲状腺素（第三四分位：调整后的 HR 1.50；95%CI，1.26 至 1.79；第四四分位：调整后的 HR 1.79；95%CI，1.51 至 2.13）的患者相比，骨折风险增加。与匹配的对照组相比，甲状腺癌患者更有可能接受骨质疏松症药物治疗（HR 1.22；95%CI，1.18 至 1.26）。在甲状腺切除术后患者中，左旋甲状腺素的高剂量和低剂量治疗均与骨折风险呈 J 型剂量依赖性增加相关。需要进一步的研究来确定如何优化促甲状腺激素（TSH）抑制以及如何筛查和管理骨折风险。
