Levothyroxine treatment and occurrence of fracture of the hip.
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.
Sheppard
Michael C
MC
Department of Medicine, The University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, United Kingdom. m.c.sheppard@bham.ac.uk
Holder
Roger
R
Franklyn
Jayne A
JA
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006620:Hip Fractures / Q000139:chemically induced* / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011336:Probability; D018570:Risk Assessment; D012307:Risk Factors; D017678:Sex Distribution; D018709:Statistics, Nonparametric; D013974:Thyroxine / Q000009:adverse effects* / Q000627:therapeutic use; D006113:United Kingdom / Q000453:epidemiology
D013974:Thyroxine