Elsevier

Bone

Volume 86, May 2016, Pages 86-90
Bone

Full Length Article
Influence of thyroid hormone therapy on the fracture rate — A claims data cohort study

https://doi.org/10.1016/j.bone.2016.03.002Get rights and content

Abstract

Introduction

It has been debated for years whether long-term thyroid hormone intake causes fractures. Not only have previous studies suffered from design limitations, they also reached contradictory conclusions. We investigated thyroid hormones (thyroxine) as a possible risk factor for fractures in a cohort of 6.7 million persons based on administrative data.

Methods

The database consists of anonymized settlement data of approximately 70 German statutory health insurances covering a time period of six years. All subjects aged 60 and above were included in the study; subjects with repeated thyroxine prescriptions were assigned to the exposure group; members without thyroxine prescriptions to the control group. Outcome was any incident fracture during a declared time period. In order to calculate fracture risk, we performed multivariate cox regression analyses to adjust for confounders.

Results

Of 798 770 subjects fulfilling the inclusion criteria, 11.7% took thyroxine regularly and belong to the exposure group. The final cox regression showed that subjects taking thyroxine have a 6.3% higher risk (HR 1.063; CI 1.046–1.080, p = < .0001) than members of the control group.

Discussion

The study supports the assumption that long term thyroxine intake leads to an increase in fracture risk among patients older than 60 years. The findings have implications for long term thyroxine treatment.

Introduction

Thyroid hormones (thyroxine) are among the most frequently prescribed drugs in Germany [1]. According to a national survey, the population prevalence for thyroxine intake is 5.1% [2]. Despite the improvement in iodine supply over the last decade [1], [3], annual prescription rates for thyroid hormones have risen [1]. In general, thyroxine is regarded highly by both doctors and patients who perceive the hormone as well tolerated and with few side effects [4].

However, for several years there has been a debate on whether long-term thyroxine therapy might increase the fracture incidence [5]. In their nested case–control study, Turner et al. showed an increased fracture rate among patients (aged 70 or more) under long-term thyroxine therapy in comparison to thyroxine patients whose prescription had ended more than 180 days earlier [6]. Still, the evidence remains contradictory [7], [8], [9], [10]. There are no large-scaled cohort studies comparing fracture risk for thyroxine patients versus non thyroxine patients.

Regarding to the potential association between thyroxine and fractures, two possible mechanisms have been suggested: The most obvious mode of action is that thyroxine leads to a decrease of bone mass [11], [12], [13] which in turn might result in osteoporosis and osteoporosis related fractures. It is unclear whether a thyroxine induced hyperthyroidism [14], [15] is required for this to happen or whether high-normal thyroxine levels can also lead to lower bone mass [16]. Another possible mode of action is hyperthyroidism induced side effects such as arrhythmia which could lead to falls resulting in fractures [17].

The aim of our study was to investigate whether the intake of thyroxine is an independent risk factor for fractures in women and men aged 60 and above.

Section snippets

Study design and study population

We performed a retrospective cohort study on the Health Risk Institute research database# [18]. The database consists of approximately 6.7 million anonymized insured persons belonging to the German statutory health insurances (SHI) covering a time period of six years (2008–2013). The Health Risk Institute database# consists of anonymized settlement data of approximately 70 SHI. In addition to sociodemographic data, the dataset contains information about drugs (prescribed by doctors and

Results

After the exclusion of 107 235 subjects meeting the exclusion criteria mentioned above, data of 798 770 subjects were eligible. The majority was female (51.8%) and, on average, 71.4 years old (reference: year 2008). While 11.7% (n = 93 252) belonged to the exposure group, 705 518 subjects (88.3%) belonged to the controls.

Descriptive comparisons showed exposed subjects to be more frequently female (79.3% vs. 48.2%; SMD 0.63) and slightly younger [age (year: mean): 70.80 vs. 71.48; SDM 0.09] than

Discussion

This study investigated the association between thyroxine intake and the development of bone fractures. An unadjusted cox regression analysis showed that subjects taking thyroxine have a 21.3% higher risk for getting a fracture than subjects without thyroxine (HR 1.213, CI 1.195–1.231, p = < .0001). This effect is less pronounced but still significant after adjustment for the confounder “age” and “sex” (HR 1.064, CI 1.048–1.080, p = < 0.001).

The results of our study are in accordance with the recent

Conclusion

Despite the limitations mentioned above, our study supports the assumption that thyroid hormones increase fracture risk among patients older than 60 years. Prospective studies with longer follow-up times are desirable in order to unambiguously answer to our research question. However, since the effect is only small to moderate, sample size and cost of such studies will be prohibitive. In our view, results from this and previous studies justify a cautious approach to prescribing thyroxine.

#The

Competing interests

Lennart Hickstein is an employee of Elsevier GmbH. Jochen Walker is an employee of Elsevier GmbH and managing director of the Health Risk Institute. Elsevier GmbH is one of the founders of the Health Risk Institute. Annika Viniol, Erika Baum, Norbert Donner-Banzhoff and Annette Becker declare that they have no conflicts of interest in the relation to this article.

Author contributorship

Annika Viniol planned the study, developed methodological approach, and wrote the manuscript. Lennart Hickstein analyzed data. Jochen Walker developed methodological approach and analyzed data. Norbert Donner-Banzhoff, Erika Baum, and Annette Becker planned the study design. All authors edited the drafted version of the manuscript.

Funding

This work was supported by human resources of the Department for primary care, University Marburg and the Health Risk Institute in Berlin.

Ethical approval

A claim data study does not require ethical approval.

Acknowledgments

We also would like to thank Mareike Künkler for providing English-language editing, improving the precision and fluency of the manuscript.

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