Low Serum DHEAS Predicts Increased Fracture Risk in Older Men: The MrOS Sweden Study

Abstract

The adrenal-derived hormones dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the most abundant circulating hormones and their levels decline substantially with age. DHEAS is considered an inactive precursor, which is converted into androgens and estrogens via local metabolism in peripheral target tissues. The predictive value of serum DHEAS for fracture risk is unknown. The aim of this study was, therefore, to assess the associations between baseline DHEAS levels and incident fractures in a large cohort of older men. Serum DHEAS levels were analyzed with mass spectrometry in the population-based Osteoporotic Fractures in Men study in Sweden (n ¼ 2568, aged 69 to 81 years). Incident X-ray validated fractures (all, n ¼ 594; non-vertebral major osteoporotic, n ¼ 255; hip, n ¼ 175; clinical vertebral, n ¼ 206) were ascertained during a median follow-up of 10.6 years. DHEAS levels were inversely associated with the risk of any fracture (hazard ratio [HR] per SD decrease ¼ 1.14, 95% confidence interval [CI] 1.05-1.24), non-vertebral major osteoporotic fractures (HR ¼ 1.31, 95% CI 1.16-1.48), and hip fractures (HR ¼ 1.18, 95% CI 1.02-1.37) but not clinical vertebral fractures (HR ¼ 1.09, 95% CI 0.95-1.26) in Cox regression models adjusted for age, body mass index (BMI) and prevalent fractures. Further adjustment for traditional risk factors for fracture, bone mineral density (BMD), and/or physical performance variables as well as serum sex steroid levels only slightly attenuated the associations between serum DHEAS and fracture risk. Similarly, the point estimates were only marginally reduced after adjustment for FRAX estimates with BMD. The inverse association between serum DHEAS and all fractures or major osteoporotic fractures was nonlinear, with a substantial increase in fracture risk (all fractures 22%, major osteoporotic fractures 33%) for those participants with serum DHEAS levels below the median (0.60 mg/mL). In conclusion, low serum DHEAS levels are a risk marker of mainly non-vertebral fractures in older men, of whom those with DHEAS levels below 0.60 mg/mL are at highest risk.

Serum DHEA and Its Sulfate Are Associated With Incident Fall Risk in Older Men: The MrOS Sweden Study

“…In summary, we demonstrate that high DHEA and DHEAS are associated with a lower fall risk in older men, independently of serum testosterone levels. Our previous studies also demonstrated that low serum levels of DHEA and/or DHEAS predict an increased risk of all cause and cardiovascular mortality, cardiovascular events, and fracture risk . Moreover, the genetic variants and related genes associated with serum DHEAS levels are connected to biological pathways linking DHEAS with aging.…”

“…Further adjustments were made for total body lean mass and grip strength (n ¼ 2402 in the combined model), narrow walk (n ¼ 2387), and the combination of lean mass, grip strength, and narrow walk (n ¼ 2292 demonstrated that low serum levels of DHEA and/or DHEAS predict an increased risk of all cause and cardiovascular mortality, (28) cardiovascular events, (29) and fracture risk. (18) Moreover, the genetic variants and related genes associated with serum DHEAS levels are connected to biological pathways linking DHEAS with aging. This suggest that the molecular pathways involved in DHEAS regulation on the one hand and aging and longevity on the other hand share common genetic components, (8) further corroborating a role for DHEA and its sulfate as markers of biological aging.…”

“…We have previously demonstrated that low serum levels of DHEA and/or DHEAS predict an increased risk of fractures in older men . Evidence supporting a role of DHEA/DHEAS for fall risk in men is, however, still lacking.…”

“…(17) We have previously demonstrated that low serum levels of DHEA and/or DHEAS predict an increased risk of fractures in older men. (18) Evidence supporting a role of DHEA/DHEAS for fall risk in men is, however, still lacking. Therefore, the aim of this study was to investigate the predictive role of serum DHEA and DHEAS levels for incident fall risk in a large population-based cohort of older Swedish men.…”

Increased risk for hip fracture after death of a spouse—further support for bereavement frailty?

“…Increased cortisol levels in the mornings occur at least in the first 6 months after bereavement, often accompanied with decreased levels of dehydroepiandrosterone (DHEA) [3]. Studies have shown an increased risk for falls and fractures in older men with low levels of DHEA [32,33]. When compared with married ones, widows were more likely to demonstrate worse coping behaviour in terms of more smoking and drinking.…”