Peggy M. Cawthon, PhD, MPH, of California Pacific Medical Center Research Institute in San Francisco, and colleagues analyzed data from 1,463 men aged at least 65 years participating in the osteoporotic fractures in men (MrOS) study who had been randomly selected for sex hormone measurements (total and bioavailable estradiol and testosterone levels, andSHBG levels); 1,054 men had follow-up data 4.6 years later. Researchers assessed vertebral fractures on lateral and thoracic radiographs completed during the study; participants completed questionnaires regarding nonspine fractures since aged 50 years, history of falls during the past 12 months, physical activity level and demographic information. Bone mineral density was measured via DXA scan; physical performance was assessed by walking speed after 6 m.
After adjusting for total estradiol and total testosterone, researchers found that higher SHBG was associated with a greater likelihood of prevalent vertebral fractures (OR = 1.38 per standard deviation increase; 95% CI, 1.11-1.72). Total estradiol analyzed as a continuous variable was not associated with prevalent vertebral fractures after adjustment for total testosterone and SHBG (OR = 0.86 per SD increase; 95% CI, 0.68-1.1). Men with total estradiol values of 17 pg/mL or less had a borderline higher likelihood of prevalent fracture than men with higher values (OR = 1.46; 95% CI, 0.99-2.16).
Neither total testosterone nor bioavailable testosterone were associated with prevalent radiographic vertebral fractures in any model, according to researchers.
“The SHBG findings are puzzling,” the researchers wrote. “It is possible that SHBG has independent effects on risk for vertebral fractures by directly influencing skeletal tissues. Although it was long considered merely a transporter for sex hormones to target cell membranes, it is now considered likely that SHBG acts directly on a variety of cell types and can be found intracellularly.”
NOTE: Is "free estradiol" the main factor that keeps strong bones? High SHBG may mean lower free E2 and lower free T.