Subclinical hyperthyroidism independent risk factor for fracture
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Subclinical hyperthyroidism is an independent risk factor associated with fracture among white and Black middle-aged adults, according to results from a community-based cohort study published in JAMA Network Open.
“A meta-analysis of 13 studies found an independent positive association between subclinical hyperthyroidism and fracture risk,” Natalie R. Daya, MPH, a PhD student in the department of epidemiology at Johns Hopkins Bloomberg School of Public Health, and colleagues wrote. “Many of the previous studies have been limited to cohorts of older and predominantly white patients, and they lack information on important confounders and the history of fracture. In addition, several studies included individuals using thyroid medications, thus limiting the literature on endogenous subclinical thyroid dysfunction.”
Researchers analyzed data from 10,946 participants (mean age, 57 years; 54.3% women) from the Atherosclerosis Risk in Communities Study, which is an ongoing prospective cohort study of community-dwelling individuals conducted from 1987 to 2019 in Maryland, North Carolina, Mississippi and Minnesota suburbs. All participants had no prescribed thyroid medications and no fracture history. Participants had thyroid-stimulating hormone and free thyroxine levels recorded in 1990-1992. Subclinical hyperthyroidism was defined as a TSH level less than 0.56 mIU/L, subclinical hypothyroidism was defined as a level more than 5.1 mIU/L and euthyroidism was defined as levels of 0.56 mIU/L to 5.1 mIU/L, with normal T4 levels from 0.85 ng/dL to 1.4 ng/dL.
The primary outcome was incident fracture obtained from hospitalization discharge codes through 2019.
Overall, 93% of participants had euthyroidism, 2.6% had subclinical hyperthyroidism and 4.4% had subclinical hypothyroidism. During a median follow-up of 21 years, researchers observed 3,556 incident fractures, which equaled 167.1 per 10,000 person-years.
Participants with subclinical hyperthyroidism (adjusted HR = 1.34; 95% CI, 1.09-1.65) had higher risk for fracture compared with participants with euthyroidism. Fracture risk was similar for participants with subclinical hypothyroidism (aHR = 0.9; 95% CI, 0.77-1.05) compared with euthyroidism. In addition, TSH levels in the lower-than-normal range were significantly associated with higher risk for fracture-related hospitalization among participants with normal T4 levels, and fracture risk was higher among participants with subclinical hyperthyroidism.
“Longitudinal studies measuring thyroid function levels at more than one time point are needed to further examine the association of the trajectory of thyroid function with subsequent risk of fracture,” the researchers wrote. “Clinical trials are needed to elucidate the mechanisms by which subclinical thyroid dysfunction may be associated with fractures and other clinical outcomes.”
Perspective
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Arti Bhan, MD, FACE
Overt hyperthyroidism is an established risk factor for osteoporosis and fractures. Several studies have demonstrated increased risk of fractures in patients with subclinical hyperthyroidism as well. Thyroid hormone has an effect on osteoclasts and osteoblasts, with higher levels correlating with accelerated bone turnover, causing bone loss and increased risk forfracture. Since subclinical hyperthyroidism remains undiagnosed for years, there is a greater length of time for adverse bone events to occur.
In this community-based cohort of 10,946 adults, endogenous subclinical hyperthyroidism conferred a higher riskfor fractures and fracture-related hospitalization, compared with euthyroid individuals. Hip and spine fractures were the most common, and those with subclinical hyperthyroidism had a 34% higher risk for fracture compared with people who were euthyroid. In addition, mortality rates were highest in the subclinical hyperthyroidism group. The strengths of this study included a younger population that included both Black and white participants, extensive adjustment for potential confounders and a long follow-up period of over 20 years.
The American Thyroid Association/American Association of Clinical Endocrinologists guidelines strongly suggest treatment for high-risk patients older than 65 years, with TSH values under 0.1 mIU/L. The findings of this study are consistent with other similar studies and support the above recommendation. The increased fracture risk occurs as a continuum, and this study suggests a potential need for closer monitoring of even younger individuals with low, but not suppressed, levels of serum TSH for ongoing bone loss.
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