Levothyroxine dose may be linked to fracture risk in older adults, study suggests

Levothyroxine, especially at higher doses, may be associated with increased fracture risk in older adults, according to a new study.

Researchers performed a nested case-control study using population-based health databases from Ontario, Canada, to examine whether levothyroxine dose affected risk of fracture in older patients. The study included adults at least 70 years of age who had been prescribed levothyroxine between April 1, 2002 and March 31, 2007. Patients were followed for fractures until March 31, 2008. Cases, defined as members of the cohort who had been hospitalized for fracture, were matched with five or fewer cohort controls who hadn't had a fracture. Fracture in relation to current, recent past, or remote use of levothyroxine was the primary outcome. Recent past use was defined as use discontinued within 15 to 180 days of the index date, while remote use was defined as use discontinued more than 180 days before the index date. The study was published online April 28 by BMJ.

Overall, the authors identified 213,511 patients who had used levothyroxine, 22,236 of whom (10.4%) had a fracture over 3.8 years of follow-up. Of those who had fracture, more than three-quarters were women. The mean patient age was 82 years. Current use of levothyroxine was associated with significantly higher fracture risk than remote use (adjusted odds ratio, 1.88 [95% CI, 1.71 to 2.05]). Patients currently taking high (>0.093 mg/d) and medium (0.044 to 0.093 mg/d) cumulative doses of levothyroxine had a statistically significantly increased risk for fracture (adjusted odds ratios, 3.45 [95% CI, 3.27 to 3.65] and 2.62 [95% CI, 2.50 to 2.76], respectively) compared with patients taking low cumulative doses (<0.044 mg/d).

The authors noted that their study did not include laboratory or radiological data and that they did not know the clinical indications for levothyroxine treatment in study participants, among other limitations. However, they concluded that in adults older than 70 years of age, a statistically significant increased risk for fracture may be linked to current use of levothyroxine, and higher doses appear to be associated with greater risk. “Our findings provide evidence that levothyroxine treatment may increase the risk of fragility fractures in older people even at conventional dosages, suggesting that closer monitoring and modification of treatment targets may be warranted in this vulnerable population,” they wrote.

The authors of an accompanying editorial agreed, calling for regular monitoring of thyroid-stimulating hormone (TSH) levels in elderly patients. “Further work is needed to see whether current TSH reference ranges (usually 0.4-4.0 mU/L) are appropriate for use in elderly people. If these ranges are not appropriate, this could theoretically exacerbate the risk of overtreatment in elderly people, with increased risk of bone loss and fractures in this high risk group,” the editorialists wrote.