Levothyroxine treatment and occurrence of fracture of the hip
Abstract
BACKGROUND: Levothyroxine sodium is widely prescribed and has been implicated as a cause of reduction in bone mineral density and, therefore, suggested to be a major contributor to the risk of osteoporotic fractures. OBJECTIVE: To investigate whether levothyroxine use increases the risk of developing osteoporotic fractures. METHODS: We conducted a population-based, case-control analysis of the risk of a femur fracture in a large cohort of patients who had been prescribed levothyroxine. We used the United Kingdom General Practice (primary care) Research Database to identify 23,183 patients who had been prescribed long-term thyroid hormone therapy and to identify for each patient taking levothyroxine 4 controls matched for age, sex, primary care practice, and duration of registration on the database. The number of patients who had sustained a fracture of the proximal femur was ascertained for each group, together with drug therapies and medical diagnoses likely to affect fracture risk. RESULTS: Of the 23,183 patients prescribed thyroid hormone, a mean +/- SE of 1.61% +/- 0.08% had sustained a fracture of the femur, compared with 1.44% +/- 0.04% of 92,732 controls (P =.06). When analyzed according to sex, a significant difference in rate of fracture between patients taking levothyroxine and controls was found in males (P =.008). Compared with controls, patients taking levothyroxine had higher reported rates of medical diagnoses and therapies, potentially confounding the fracture risk. Independent predictors of the occurrence of fracture after adjustment for other factors were age (adjusted odds ratio [AOR], 1.11; 95% confidence interval [CI], 1.10-1.11; P<.001), medical diagnoses including rheumatoid arthritis (AOR in females, 1.69; 95% CI, 1.27-2.26; P<.001), excessive use of alcohol (AOR in females, 3.05; 95% CI, 1.94-4.76; P<.001), and prescription of drugs (eg, anticonvulsants; AOR in females, 2.49; 95% CI, 2.00-3.09; P<.001). Prescription of levothyroxine was an independent predictor of fracture occurrence in males (AOR, 1.69; 95% CI, 1.12-2.56; P =.01) but not females (AOR, 1.03; 95% CI, 0.92-1.16; P =.60). CONCLUSIONS: The lack of association between fracture and levothyroxine prescription in the whole cohort is reassuring, although an independent association between levothyroxine prescription and fracture occurrence in male patients suggests that levothyroxine may contribute to fracture risk in this specific group.
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Secondary analyses of other studies have only found associations between levothyroxine replacement and hip fractures in men and forearm fractures in older adults within the first two years of treatment.
“Secondary analyses of other studies have only found associations between levothyroxine replacement and hip fractures in men27 and forearm fractures in older adults within the first two years of treatment.29”
From Levothyroxine dose and risk of fractures in older adults: nested case-control study (2011) · cites this paper as [27]
A large UK GPRD study found increased proximal femur fracture risk in male but not female LT4 users.
“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)”
Taken together, the evidence suggests patients with hypothyroidism as a group may not have a clinically relevant increased osteoporotic fracture risk.
“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.”
Observational studies in the United Kingdom and the United States reported an increased fracture risk in men but not women treated for hypothyroidism.
“An increased risk in men but not women treated for hypothyroidism was also reported from observational studies in both the United Kingdom (17) and the United States.(18)”
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Thyroid disorders and bone disease
Cheung, M., Gogakos, A. I., Bassett, J. H. D., & Williams, G. R. (2011) · doi:10.1093/med/9780199235292.003.0465
- Authors
- Sheppard, M. C., Holder, R., & Franklyn, J. A.
- Affiliations
- Queen Elizabeth Hospital Birmingham (GB)
- Venue
- Archives of Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2002-02-11
- Volume
- 162
- Issue
- 3
- Pages
- 338
- ISSN
- 0003-9926 (ISSN-L)
- OpenAlex
- W2058131123
- Cited by
- 56
- References
- 28
- Citations by year
- 2024: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 1 · 2012: 3
- FWCI
- 5.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Keywords
- levothyroxine, hip fracture, femoral fracture, osteoporotic fractures, thyroid hormone replacement, fracture risk, bone mineral density, rheumatoid arthritis, alcohol consumption, antiepileptic drugs, confounding factors, sex differences, primary care patients, age as risk factor, case-control study, adverse drug reactions
- MeSH terms
- Adult, Aged, Aged, 80 and over, Dose-Response Relationship, Drug, Female, United Kingdom, Hip Fractures, Humans, Male, Middle Aged, Probability, Risk Factors, Thyroxine, Cohort Studies, Incidence, Confidence Intervals, Logistic Models, Case-Control Studies, Age Distribution, Sex Distribution, Risk Assessment, Statistics, Nonparametric
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