Individuals with subclinical hyperthyroidism are at increased risk of hip and other fractures, according to the authors of a meta-analysis .

Researchers examined data from 70,298 individuals – 4,092 with subclinical hypothyroidism and 2,219 with subclinical hyperthyroidism – enrolled in 13 prospective cohort studies.

After adjusting for age, sex, and other fracture risk factors, the researchers found that individuals with subclinical hyperthyroidism had a 28% increase in the risk of any fracture and a 36% increased risk of hip fracture compared to individuals with normal thyroid function.

Subclinical hyperthyroidism – defined as a thyroid-stimulating hormone (TSH) level of less than 0.45 mIU/L with normal FT4 levels – was also associated with a 16% increase in the risk of nonspine fracture, according to a paper published online in the May 26 edition of JAMA.

Men with subclinical hyperthyroidism had a more than 3.5-fold increased in the risk of spine fracture, but the increase was not significant in women.

Lower TSH was associated with higher fracture rates, and the analysis showed a 61% increase in the risk of hip fracture and more than a 3.5-fold increase in spine fracture risk among individuals with a TSH less than 0.10 mIU/L.

The analysis yielded no link between subclinical hypothyroidism and fracture risk, and a comparison of fracture risk between individuals treated with thyroxine at baseline and untreated participants also showed no impact of thyroxine therapy on fracture outcomes ( JAMA 2015, May 26 [doi:10.1001/jama.2015.5161].

“In prospective cohort studies, data about the association between subclinical thyroid dysfunction and fracture risk are in conflict because of inclusion of participants with overt thyroid disease and small sample sizes of participants with thyroid dysfunction or fracture events,” wrote Dr. Manuel R. Blum of Bern University Hospital, Switzerland, and an international team of coauthors.

They proposed three mechanisms by which thyroid dysfunction may affect fracture risk.

“First, thyroid hormones have been shown to have effects on osteoclasts and osteoblasts, with thyroid status in the upper normal range or excess thyroid hormones leading to accelerated bone turnover with bone loss and increased fracture risk,” they wrote.

Subclinical hyperthyroidism may also increase the risk of falls by affecting muscle strength and coordination, and thyroxine supplementation was also suggested as impacting fracture risk.

“Endogenous subclinical hyperthyroidism may be undetected for years because symptoms of subclinical hyperthyroidism are often nonspecific or absent,” the authors wrote. “This phenomenon has the potential to lead to a greater length of time for adverse associations with bone metabolism.”

The authors stressed the limitations of the observational data; for example, that thyroid function was assessed only at baseline and that some individuals may have progressed to overt thyroid dysfunction over the course of the study, and a lack of uniform definition of fracture type across the cohorts.

They said their findings supported current guideline recommendations that anyone aged 65 years or older, with subclinical hyperthyroidism and a TSH persistently lower than 0.1 mIU/L, should be treated, and treatment should be considered in those individuals with low TSH but still above 0.1 mIU/L.

The Swiss National Science Foundation and Swiss Heart Foundation supported the study. Some authors disclosed personal fees, grants and funding from a range of pharmaceutical companies.


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