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Excessive levothyroxine intake raised fracture risk in older adults
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Adults aged 70 years and older who take high doses of levothyroxine appear to be at increased risk for fractures.
This finding prompted researchers to call for re-examination of recommended thyroid hormone doses and closer monitoring of usage in this older population.
Previous studies investigating an association between levothyroxine and fracture risk have yielded unclear results, and none have evaluated a relationship between dosage and fracture risk, according to researchers in Toronto. They conducted a nested case-control study using data from population-based health databases in Ontario, Canada. Patients’ age ranged from 70 to 105 years, and all had at least one prescription for levothyroxine between 2002 and 2007.
The study identified 213,511 prevalent thyroxine users. Of these, 10.4% experienced at least one fracture during a mean follow-up of 3.8 years. Results suggested that current levothyroxine use compared with past use was associated with a considerably higher risk for fracture (adjusted OR=1.88; 95% CI, 1.71-2.05).
Further, data linked higher doses among current users with significantly elevated risk for fracture. Compared with those receiving daily cumulative doses of less than 0.044 mg daily, the risk for fracture was considerably higher among patients using more than 0.093 mg daily (adjusted OR=3.45; 95% CI, 3.27-3.65) or between 0.044 mg and 0.093 mg daily (adjusted OR=2.62; 95% CI, 2.5-2.76).
“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,” the researchers wrote.
In an accompanying editorial, Graham P. Leese, MD, of Ninewells Hospital and Medical School in Dundee, United Kingdom, said ideal doses may change as patients age.
“Current evidence suggests that elderly people need relatively low thyroxine doses, so serum thyroid-stimulating hormone should be regularly monitored and a suppressed TSH should be avoided in such patients,” he said. “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.”
Leese also highlighted the importance of future research in this area.
“It is 120 years since the effect of excess thyroid hormone on bone was first described, yet research in this area still lacks funding,” he said. “With the prevalence of treated hypothyroidism increasing … such research warrants a higher priority.” – by Melissa Foster
For more information:
Disclosure: Dr. Leese reports no relevant financial disclosures.
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This study by Turner et al adds to our general knowledge regarding the increased likelihood of spine and hip fractures in adults at least 70 years old who are currently taking exogenous levothyroxine, with the risk increasing with higher doses. Data were accrued from the Ontario Drug Benefit database and a retrospective, nested case-control design was employed. The population analyzed was large (n=213,511); fractures were relatively common; and statistical adjustments were performed for multiple variables. The database did not, however, contain information regarding relevant fracture risk factors, BMI, levothyroxine compliance or serum levels of 25-hydroxyvitamin D, free thyroxine or thyroid-stimulating hormone.
Nonetheless, an important clinical extrapolation is that, given the increased risk of fractures in this population, efforts should be employed to monitor bone mineral density periodically to assess risk factors in elderly patients taking exogenous levothyroxine. Prophylactic measures should be utilized, such as calcium, vitamin D, exercise, and serum levels of 25-hydroxyvitamin D, FT4 and TSH should be monitored to ensure they are appropriate for clinical context.
– Kenneth D. Burman, MD
Chief, Endocrine
Section
Washington Hospital Center
Professor, Department of Medicine
Georgetown University
Disclosure: Dr. Burman reports no relevant financial disclosures.
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