This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (15)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Adverse Effects  • Alert me on articles by topic  Social Bookmarking   What's this?

Michael C. Sheppard, MB, PhD; Roger Holder, BSc; Jayne A. Franklyn, MD, PhD

Arch Intern Med. 2002;162:338-343.

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.

From the Departments of Medicine (Drs Sheppard and Franklyn) and Statistics (Mr Holder), The University of Birmingham, Birmingham, United Kingdom.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

The Clinical Significance of Subclinical Thyroid Dysfunction
Biondi and Cooper
Endocr. Rev. 2008;29:76-131.
ABSTRACT | FULL TEXT  

Thyroid hormone in health and disease
Boelaert and Franklyn
J Endocrinol 2005;187:1-15.
ABSTRACT | FULL TEXT  

Subclinical hyperthyroidism: clinical features and treatment options
Biondi et al.
Eur J Endocrinol 2005;152:1-9.
ABSTRACT | FULL TEXT