Background: Patients with chronic kidney disease (CKD) are at increased fracture risk. In men without CKD, oestradiol is the predominant sex hormone regulating bone health, but sex hormone binding globulin (SHBG) has also been independently associated with fracture. Gonadal dysfunction is common in men receiving dialysis, however the effect of sex-steroids and SHBG on bone mineral density (BMD) and fracture in these patients is unknown.
Aim: To examine the relationship between gonadal steroids and SHBG with BMD and fractures in men receiving dialysis pre-transplantation.
Methods: Cross-sectional study of male dialysis patients wait-listed for transplantation. Biochemistry, gonadal steroids (oestradiol, total testosterone (TT), calculated free testosterone (FT)), SHBG, dual-energy X-ray absorptiometry and thoracolumbar X-rays were performed prior to transplantation. Multivariable regression models were used to investigate the associations between gonadal steroids, BMD and fractures.
Results: 546 males (mean age 45.8 ± 12.8 years) were included. Pre-existing diabetes mellitus was present in 38% and median time of dialysis was 24months. 183 patients had non-vertebral fractures (23%), 92 (17%) had vertebral fractures and 59 (11%) had both. After adjusting for age, BMI and dialysis time, higher SHBG levels were associated with non-vertebral fractures, even after adjusting for femoral neck (FN) Z-scores (OR 1.65; 95% CI 1.08-2.53, p=0.022). Oestradiol, TT and FT were not associated with vertebral or non-vertebral fractures. SHBG was also associated with lumbar spine (LS) and FN Z-scores using the same adjusted models (β=-0.181, p=0.019 and β= -0.204 p=0.018 respectively). Lower oestradiol levels were significantly correlated with lower LS Z-scores (β=0.137, p=0.014) and adjusting for diabetes mellitus did not attenuate these associations.
Conclusion: Fractures occur in about half of men receiving pre-transplantation dialysis and associated with higher SHBG levels, but not oestradiol or TT/FT. The role of SHBG as a novel biomarker of bone health in male patients receiving dialysis warrants further investigation.