Increased Risk of Falls and Increased Bone Resorption in Elderly Men with Partial Androgen Deficiency: The MINOS Study

Abstract

AbstractThe goal of this study was to identify the clinical and biological patterns of hypogonadism in a cohort of 1040 elderly men. Residual androgenic activity was estimated by total testosterone as well as the apparent free testosterone concentration (AFTC) and free testosterone index (FTI) calculated on the basis of concentrations of SHBG and total testosterone using appropriate formulae. The lower limit of the normal range defined by 2 sd below the mean in 150 healthy, nonobese, and nonsmoking men, aged 19–40 yr, was calculated for total testosterone (9.26 nmol/liter), AFTC (146 pmol/liter), and FTI (0.14 nmol/nmol). The prevalence of hypogonadism increased with ageing. Hypogonadal men were older and heavier (due to a higher fat body mass) and had lower concentrations of 17β-estradiol and androstenedione than men with normal androgenic activity. Men with decreased AFTC had a slightly lower bone mineral density (BMD) at certain sites. Men with decreased FTI had lower appendicular skeletal muscle mass and relative skeletal muscle index. For all three measures of androgenic activity, hypogonadal men had increased levels of the markers of bone resorption. In the multiple regression models including both 17β-estradiol and testosterone (total, AFTC, or FTI), 17β-estradiol was the only significant determinant of BMD. In the multiple regression models including 17β-estradiol and AFTC or FTI, only testosterone was a significant determinant of the variability in bone formation markers, whereas both 17β-estradiol and testosterone were significant determinants of the variability of the markers of bone resorption. Hypogonadism was associated with an increase in the risk of falls, an impairment of static and dynamic balance, as well as the inability to stand up from a chair and to perform the tandem walk. Decreased AFTC (<146 pmol/liter) discriminated best men with functional disabilities (odds ratio, 1.54–7.95; P < 0.05–0.0001). Hypogonadal elderly men had increased bone resorption that was not adequately matched by an increase in bone formation, lower muscle strength, impaired static and dynamic balance, a higher risk of falls, and, in men with low AFTC, a slightly lower BMD. Low AFTC seems to have the best discriminative power for densitometric, biochemical, and functional parameters, followed by FTI, whereas total testosterone was the least discriminative. In multiple regression models, 17β-estradiol was the strongest determinant of BMD, and AFTC and FTI were significant determinants of the variability in bone formation markers, whereas both 17β-estradiol and testosterone determined the variability in bone resorption markers.