Risk of osteoporosis in thyroid cancer patients using levothyroxine: a population-based study

Abstract

Background: The outcomes of thyroid cancer patients using levothyroxine are largely undetermined.

Methods: The study population consisted of 9398 patients newly diagnosed with thyroid cancer; their data was retrieved from a subset of the National Health Insurance Research Database of Taiwan during the period of 1999–2011. In this nationwide retrospective cohort study, we compared the risk of osteoporosis among thyroid cancer patients with levothyroxine use, those without levothyroxine use, and propensity-score-matched non-thyroid controls. We also investigated the duration–response and dose–response relationships between levothyroxine use and the risk of osteoporosis. The competing risk was also analyzed.

Results: The mean duration of follow-up was 6.63 years for patients without thyroid cancer, 5.45 years for thyroid cancer patients without levothyroxine use, and 6.46 years for thyroid cancer patients with levothyroxine use. The incidence of osteoporosis was higher in the thyroid cancer cohort than in the non-thyroid-cancer cohort (8.69 vs. 6.60 per 1000 person-years, respectively), with an adjusted hazard ratio of 1.39 (95% confidence interval [CI] = 1.22–1.58). Thyroid cancer patients with levothyroxine use exhibited a significantly higher risk of osteoporosis than non-thyroid-cancer patients, while thyroid cancer patients not using levothyroxine did not have significant higher risks than non-thyroid-cancer patients. Compared with patients without thyroid cancer, the risk of osteoporosis increased from 1.53 (95% CI = 0.91–2.57) in patients receiving a cumulative dose of ≤265 mg levothyroxine, to 3.62 in those receiving a cumulative dose of >395 mg levothyroxine (95% CI = 2.16–6.06).

Conclusion: Our population-based cohort study showed that thyroid cancer patients receiving levothyroxine have a higher risk of osteoporosis.

Keywords:

• Thyroid cancer
• levothyroxine
• osteoporosis
• cohort study

Transparency

Declaration of funding

This study was supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW106-TDU-B-212-113004), China Medical University Hospital, Academia Sinica Taiwan Biobank Stroke Biosignature Project (BM10601010036), Taiwan Clinical Trial Consortium for Stroke (MOST 106-2321-B-039-005), Tseng-Lien Lin Foundation, Taichung, Taiwan, Taiwan Brain Disease Foundation, Taipei, Taiwan, and Katsuzo and Kiyo AoshimaMemorial Funds, Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.

Author contributions: All authors have contributed significantly, and all authors agree with the manuscript content. Conception/design: S.-Y.L., C.-H.K.; provision of the study materials: C.-H.K.; collection, assembly of data, or both: all authors; data analysis and interpretation: all authors; manuscript writing: all authors; final approval of the manuscript: all authors.

Declaration of financial/other relationships

S.-Y.L., C.-L.L., H.-T.C. and C.-H.K. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW106-TDU-B-212-113004), China Medical University Hospital, Academia Sinica Taiwan Biobank Stroke Biosignature Project (BM10601010036), Taiwan Clinical Trial Consortium for Stroke (MOST 106-2321-B-039-005), Tseng-Lien Lin Foundation, Taichung, Taiwan, Taiwan Brain Disease Foundation, Taipei, Taiwan, and Katsuzo and Kiyo AoshimaMemorial Funds, Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.