Subclinical Thyroid Dysfunction and Incident Hip Fracture in Older Adults

Abstract

Background Subclinical thyroid dysfunction is common in older adults and affects bone metabolism, but its effects on fracture risk have not been reported. We sought to determine prospectively whether older men and women with subclinical hyperthyroidism or hypothyroidism have an increased risk of hip fracture. Methods Prospective cohort of 3567 US community-dwelling adults, 65 years or older, with biochemically defined subclinical thyroid dysfunction or euthyroidism was enrolled from June 10, 1989, through May 30, 1990, and followed up through 2004. Main outcome measures included incidence and hazard ratios (HRs), with 95% confidence intervals (CIs), of confirmed incident hip fractures for groups with subclinical hypothyroidism, subclinical hyperthyroidism, and euthyroidism as defined at baseline. Results During 39 952 person-years (median follow-up, 13 years), hip fracture incidence (per 1000 men-years) was 13.65 in men with subclinical hyperthyroidism (n = 29) and 10.27 in men with subclinical hypothyroidism (n = 184), both greater than 5.0 in men with euthyroidism (n = 1159). Men with subclinical hypothyroidism had a multivariable-adjusted HR of 2.31 (95% CI, 1.25–4.27); those with subclinical hyperthyroidism, 3.27 (0.99–11.30). After excluding those with baseline use of thyroid-altering medications, men with endogenous subclinical hyperthyroidism had a higher HR of 4.91 (95% CI, 1.13–21.27), as did men with endogenous subclinical hypothyroidism (2.45, 1.27–4.73). Hip fracture incidence (per 1000 women-years) was 8.93 in women with subclinical hypothyroidism (n = 359) and 10.90 in women with subclinical hyperthyroidism (n = 142) compared with 10.18 in women with euthyroidism (n = 1694). No clear association between subclinical dysfunction and fracture was observed in women. Conclusions Older men with subclinical hyperthyroidism or hypothyroidism are at increased risk for hip fracture. Whether treatment of the subclinical syndrome reduces this risk is unknown.

Prevalence of silent vertebral fractures detected by vertebral fracture assessment in young Portuguese men with hyperthyroidism

“…Several studies carried out in patients with iatrogenic hyperthyroidism showed that the risk for fracture was higher in older men and mainly in women with a very low TSH level (30,31,32). However, it is not totally clear that iatrogenic hyperthyroidism does affect bone in a totally similar way as hyperthyroidism due to toxic goiter or autoimmune diseases.…”

The Excess Risk of Major Osteoporotic Fractures in Hypothyroidism Is Driven by Cumulative Hyperthyroid as Opposed to Hypothyroid Time: An Observational Register-Based Time-Resolved Cohort Analysis

“…An increased risk in men but not women treated for hypothyroidism was also reported from observational studies in both the United Kingdom (17) and the United States. (18) Because the effects of more pronounced hypothyroidism include lowering of gonadotropin and sex hormone levels in otherwise eugonadal subjects, a state of mild or moderate central hypogonadism with low testosterone levels could ensue in men. (30) This could contribute to the observed increased fracture risk seen in younger and middle-aged men-an association that was absent in those >75 years old.…”

Does thyroid function influence fracture risk? Prospective data from the HUNT2 study, Norway

“…Both overt hypothyroidism and hyperthyroidism have been associated with increased risk of fractures in previous studies (6,7,8,9,10,11,12,13,14). Other studies have reported that fractures are more common in persons with subclinical thyroid dysfunction (15,16), and some have found fracture incidence to increase by decreasing thyroid-stimulating hormone (TSH) within the reference range (13,17,18). However, the results of these and other studies are inconsistent (7,13,14,19,20).…”