Levothyroxine dose and risk of fractures in older adults: nested case-control study

Turner, Marci R; Camacho, Ximena; Fischer, Hadas D.; Austin, Peter C.; Anderson, Geoff; Rochon, Paula A.; Lipscombe, Lorraine L.

doi:10.1136/bmj.d2238

Cited by 120 publications

(85 citation statements)

References 71 publications

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“…Several studies carried out in patients with iatrogenic hyperthyroidism showed that the risk for fracture was higher in older men and mainly in women with a very low TSH level (30,31,32). However, it is not totally clear that iatrogenic hyperthyroidism does affect bone in a totally similar way as hyperthyroidism due to toxic goiter or autoimmune diseases.…”

Section: Discussionmentioning

confidence: 91%

Prevalence of silent vertebral fractures detected by vertebral fracture assessment in young Portuguese men with hyperthyroidism

Barbosa¹,

Mascarenhas²,

Silva³

et al. 2015

European Journal of Endocrinology

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Background: Hyperthyroidism is a risk factor for reduced bone mineral density (BMD) and osteoporotic fractures. Vertebral fracture assessment (VFA) by dual-energy X-ray absorptiometry (DXA) is a radiological method of visualization of the spine, which enables patient comfort and reduced radiation exposure. Objectives: This study was carried out to evaluate BMD and the prevalence of silent vertebral fractures in young men with hyperthyroidism. Design: We conducted a cross-sectional study in a group of Portuguese men aged up to 50 years and matched in hyperthyroidism (nZ24) and control (nZ24) groups. Materials and methods: A group of 48 Portuguese men aged up to 50 years was divided and matched in hyperthyroidism (nZ24) and control (nZ24) groups. BMD (g/cm 2 ) at L 1 -L 4 , hip, radius 33%, and whole body as well as the total body

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Section: Discussionmentioning

confidence: 91%

Prevalence of silent vertebral fractures detected by vertebral fracture assessment in young Portuguese men with hyperthyroidism

Barbosa¹,

Mascarenhas²,

Silva³

et al. 2015

European Journal of Endocrinology

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“…Moreover, recent evidence suggests an increased fracture risk at usual doses in older L-T4 users (> 70 years) (195) …”

Section: How To Initiate and Adjust Doses In Elderly And In Patients mentioning

confidence: 99%

Clinical practice guidelines for the management of hypothyroidism

Brenta

Vaisman

Sgarbi

et al. 2013

Arq Bras Endocrinol Metab

124

123

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Introduction: Hypothyroidism has long been known for its effects on different organ systems, leading to hypometabolism. However, subclinical hypothyroidism, its most prevalent form, has been recently related to cardiovascular risk and also to maternal-fetal complications in pregnant women. Objectives: In these clinical practice guidelines, several aspects of this field have been discussed with the clear objectives of helping physicians treat patients with hypothyroidism, and of sharing some of our Latin American-based clinical experience. Materials and methods: The Latin American Thyroid Society commissioned a Task Force on Hypothyroidism to develop evidence-based clinical guidelines on hypothyroidism. A systematic review of the available literature, focused on the primary databases of MedLine/PubMed and Lilacs/SciELO was performed. Filters to assess methodological quality were applied to select the best quality studies. The strength of recommendation on a scale from A-D was based on the Oxford Centre for Evidence--based Medicine, Levels of Evidence 2009, allowing an unbiased opinion devoid of subjective viewpoints. The areas of interest for the studies comprised diagnosis, screening, treatment and a special section for hypothyroidism in pregnancy. Results: Several questions based on diagnosis, screening, treatment of hypothyroidism in adult population and specifically in pregnant women were posed. Twenty six recommendations were created based on the answers to these questions. Despite the fact that evidence in some areas of hypothyroidism, such as therapy, is lacking, out of 279 references, 73% were Grade A and B, 8% Grade C and 19% Grade D. Conclusions: These evidence-based clinical guidelines on hypothyroidism will provide unified criteria for management of hypothyroidism throughout Latin America. Although most of the studies referred to are from all over the world, the point of view of thyroidologists from Latin America is also given. Arq Bras Endocrinol Metab. 2013;57(4):265-99

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“…Thus, a large study using data from the UK General Practice Research Database (GPRD) database found increased proximal femur fracture risk in male but not female LT4 users, (17) which was since confirmed in a prospective study in the United States, which also found increased hip fracture risk in the male but not the female patients. (18) A Canadian observational study reported a significantly increased risk of fractures in both elderly men and women when treated with LT4 (19) though no excess risk was found in men and women with subclinical hypothyroidism in the recent report from the U.S. Cardiovascular Health Study. (20) Taken together, the evidence base suggests that patients with hypothyroidism as a group may not be at a clinically relevant increased risk of osteoporotic fractures.…”

Section: Introductionmentioning

confidence: 99%

The Excess Risk of Major Osteoporotic Fractures in Hypothyroidism Is Driven by Cumulative Hyperthyroid as Opposed to Hypothyroid Time: An Observational Register-Based Time-Resolved Cohort Analysis

Abrahamsen

Jørgensen

Laulund

et al. 2014

Journal of Bone and Mineral Research

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The long-term relationship between hypothyroidism and fracture risk is challenging to dissect because of the modifying influence of subsequent thyroxine replacement with the potential for excessive replacement doses. We studied changes in serum thyrotropin concentration (TSH) over time and association with fracture risk in real-world patients presenting with elevated TSH. All TSH determinations were done in the same laboratory, which served all hospitals and general practices. The study population consisted of all adults with a first measurement of TSH >4.0 mIU/L (n ¼ 8414) or normal TSH (n ¼ 222,138; comparator). We used a Cox proportional hazards analysis incorporating additional time-dependent covariates to represent initiation of thyroxine replacement and cumulative number of periods with high versus low TSH after index date with a mean follow-up of 7.2 years. Elevated baseline TSH was not associated with an increased risk of hip fracture (HR 0.90; 95% CI, 0.80 to 1.02) or major osteoporotic fractures (HR 0.97; 95% CI, 0.90 to 1.05), nor was subsequent thyroxine prescription predictive of increased risk of fractures. The number of subsequent 6-month periods with low TSH-suggesting excessive thyroxine dosing-was significantly associated with increased risk of both hip fracture (HR 1.09; 95% CI, 1.04 to 1.15) and major osteoporotic fracture (HR 1.10; 95% CI, 1.06 to 1.14). When gender-and agestratified analyses for major osteoporotic fractures were undertaken, hyperthyroid time was identified as a predictor of fracture risk in postmenopausal women whereas hypothyroid time predicted increased fracture risk in men below age 75 years. In conclusion, among patients who present with an elevated TSH, the long-term risk of hip and other osteoporotic fractures is strongly related to the cumulative duration of periods with low TSH-likely from excessive replacement. An independent effect of elevated TSH could only be observed in young and middle-aged men, suggesting gender-discrepant consequences on risk.

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Levothyroxine dose and risk of fractures in older adults: nested case-control study

Abstract: Objective To quantify the effect of levothyroxine dose on risk of fractures in older adults. Design Nested case-control study.

Cited by 120 publications

References 71 publications

Prevalence of silent vertebral fractures detected by vertebral fracture assessment in young Portuguese men with hyperthyroidism

Prevalence of silent vertebral fractures detected by vertebral fracture assessment in young Portuguese men with hyperthyroidism

Clinical practice guidelines for the management of hypothyroidism

The Excess Risk of Major Osteoporotic Fractures in Hypothyroidism Is Driven by Cumulative Hyperthyroid as Opposed to Hypothyroid Time: An Observational Register-Based Time-Resolved Cohort Analysis

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