Older adults currently taking thyroxine replacement are at increased risk of bone fracture, compared with people who have not taken levothyroxine for 6 months or longer, Canadian researchers have found, with people currently taking more than 0.093 mg/day at the highest risk.
Excess levothyroxine and hyperthyroidism are associated with lower bone density as well as other risk factors for falls and fractures; however, the study is the first to examine the effect of levothyroxine dose on fractures in older adults.
The findings, published April 29 in BMJ (doi:10.1136/bmj.d2238), suggest that people over age 70 years would benefit from ongoing monitoring of their levothyroxine dose to avoid overtreatment and reduce fracture risk. More than a fifth of older people receive levothyroxine replacement long term, most of them women.
For their research, Dr. Marci Turner of the University of Toronto and her colleagues used a population-based health database to identify cohort of 213,511 adults aged 70 years or older who were prescribed levothyroxine during 2002-2007; follow-up lasted until 2008.
The study used a nested case-control design: Cases were cohort members admitted to the hospital for any bone fracture, matched with up to five controls from within the cohort who had not yet had a fracture for age, sex, and levothyroxine use. Of all the subjects with fractures over a mean 3.8 years of follow-up, 22,236, or 10.4%, women accounted for 88% of the fractures.
Dr. Turner and her colleagues looked at the risks associated with current levothyroxine use, compared with use that had terminated before a fracture. They found a significant increased risk (odds ratio, 1.88) for current users, compared with those who had terminated treatment more than 6 months before.
In addition to finding that current users were more likely to have a fracture than were those who had stopped levothyroxine more than 6 months before, high (mean greater than 0.093mg/day) and medium (0.044-0.093 mg/day) cumulative doses of levothyroxine were associated with a significantly increased risk of fracture among current users, compared with doses of less than 0.044 mg/day. High doses were associated with a 3.5-fold increased risk and medium doses with 2.6-fold higher risk of fracture, compared with low doses, the investigators found.
"Dosages commonly used in clinical practice, especially over 0.093 mg a day, may be excessive for this population," Dr. Turner and colleagues wrote in their analysis. "While further work is needed ... our study raises concerns that levothyroxine treatment targets may need to be modified in elderly people and that dose monitoring remains essential even into older age."
The authors cited as limitations of their study its observational design, the fact that prescribing information might have been incomplete, and that laboratory and radiology reports were not available. Other potentially confounding information, such as body mass index, family history of fractures, smoking, caffeine or alcohol use, or nonprescription drug use, was not available to the researchers.
The study was funded by the Canadian Institutes of Health Research, and Dr. Turner and her colleagues declared that they had no conflicts of interest.