Background: Circulating levels of total oestradiol (E2) decrease with age in adult males; the effect of altered E2 circadian rhythm is uncertain. We hypothesised that age-related changes in the circadian rhythm contribute to decreased BMD in older males and investigated this.
Methods: Nineteen subjects were studied: six young-healthy (YH) males (mean age (years) 27.3±4.6) with normal BMD, eight older-healthy (OH) males (mean age (years) 70.5±2.1) with normal BMD, and five older males with osteoporosis (OO) (mean age (years) 75±2.9). Groups were matched for body weight and BMI; subjects excluded had histories of bisphosphonate, corticosteroid, calcium, and/or vitamin D use and skeletal disorders. Volunteers were hospitalised with blood samples obtained every 30 min over a 24-h period. Levels of total E2 and bioavailable E2 were calculated. Circadian rhythm was analysed.
Results: Total 24-h mean bioavailable E2 was less in the OH cohort compared to the YH group (16.7±2.2 pmol/l vs 26.3±3.6 pmol/l; P<0.0001); 24-h mean total E2 concentrations reflected this pattern (P<0.0001). The OO group had significantly less 24-h mean bioavailable E2 than the OH cohort (12.5±1.8 pmol/l vs 16.7±2.2 pmol/l; P<0.0001). IGF1 levels were significantly greater in the OH compared to the OO cohorts (group mean MESOR 112±24 μg/l vs 72±13 μg/l). Total oestrogen demonstrated a concerted circadian rhythm in all three groups, but bioavailable oestrogen did not demonstrate circadian rhythmicity in older men with decreased BMD.
Conclusion: Twenty-four hours mean bioavailable E2 and IGF1 levels are significantly lower in older men with osteoporosis compared to healthy counterparts. Osteoporotic subjects demonstrated a disrupted circadian rhythm with respect to bioavailable oestrogen. Our study demonstrates the role of circadian E2 rhythms in the maintenance of BMD.