Relationship of volumetric BMD and structural parameters at different skeletal sites to sex steroid levels in men

In a population-based, cross-sectional study, we related age-associated changes in vBMD and in bone structural parameters to circulating bioavailable estradiol and testosterone levels in men. Associations between these bone mass/structural parameters and sex steroid levels were progressively stronger with age. Our previously postulated "threshold" for skeletal estrogen deficiency was most evident at cortical sites. Introduction: Serum sex steroids, particularly estrogen levels, are associated with bone mass in men, and previous work has suggested that there may be a "threshold" bioavailable estradiol (bio E₂) level below which the male skeleton becomes estrogen deficient. However, previous studies addressing this issue have exclusively used DXA, which cannot separate trabecular from cortical bone or provide information on bone geometry or structure. Materials and Methods: In an age-stratified population sample of 314 men (age, 22-91 years), we assessed volumetric BMD (vBMD) and bone geometry by QCT at the lumbar spine, femoral neck, distal radius, and distal tibia and related these to circulating bio E₂ and bio testosterone (T) levels. Results: Compared with young men (age, 20-39 years), middle-aged men (age, 40-59 years) had significantly lower bio T (-26%, p < 0.001) and bio E₂ (-9%, p = 0.038) levels, and these decreases were even greater in the elderly men (age ≥ 60 years, -60% and -38% for bio T and bio E₂, respectively, p < 0.001 for both). Reflecting their intact gonadal status, vBMD/structural parameters were not related to sex steroid levels in young men, whereas bio E₂ levels were associated consistently with vBMD and variably with bone geometric parameters in the elderly men; middle-aged men showed associations with bio E₂ and bio T at some sites. At all cortical sites, vBMD was associated with bio E₂ at low (< 30 pM, R = 0.27-0.41, p < 0.05-0.001) but not high (≥ 30 pM, R = -0.003 to 0.12, p = not significant) levels; no such differences were evident at trabecular sites. Conclusions: In men, bio E₂ is the most consistent predictor of vBMD and some bone geometric variables as assessed by QCT. We also extend our previous findings on a possible "threshold" for skeletal estrogen deficiency by showing that this is most evident for cortical sites.