Oral 63rd Endocrine Society of Australia Annual Scientific Meeting 2020

Effect of Testosterone treatment on bone microarchitecture and bone mineral density in men: a two-year randomised clinical trial (#27)

Mark Ng Tang Fui 1 2 , Rudolf Hoermann 2 , Karen Bracken 3 , David J Handelsman 4 5 , Warrick J Inder 6 7 , Bronwyn GA Stuckey 8 9 , Bu B Yeap 10 11 , Ali Ghasem-Zadeh 2 , Rob McLachlan 12 , Kristy P Robledo 3 , David Jesudason 13 14 , Jeffrey D Zajac 1 2 , Gary A Wittert 13 14 , Mathis Grossmann 1 2
  1. Austin Health, Heidelberg, Victoria, Australia
  2. Medicine, University of Melbourne, Heidelberg, Victoria, Australia
  3. NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia
  4. ANZAC Research Institute, University of Sydney , Sydney, New South Wales, Australia
  5. Department of Andrology, Concord Hospital, Concord, New South Wales, Australia
  6. University of Queensland, St Lucia, Queensland, Australia
  7. Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
  8. Keogh Institute for Medical Research, University of Western Australia, Nedlands, Western Australia, Australia
  9. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
  10. Medical School, University of Western Australia, Nedlands, Western Australia, Australia
  11. Department of Endocrinology and Diabetes, Fiona Stanley Hospital , Perth, Western Australia, Australia
  12. Hudson Institute of Medical Research, Clayton, Victoria, Australia
  13. Freemasons Foundation Centre for Men’s Health, University of Adelaide, Adelaide, South Australia, Australia
  14. The Queen Elizabeth Hospital, Woodville South, South Australia, Australia

Importance: Testosterone (T) treatment increases bone mineral density (BMD) in men, but its effects on bone microarchitecture, a determinant of fracture risk, are unknown.

Objective:  To determine the effect of T treatment on bone microarchitecture using high resolution-peripheral quantitative computed tomography (HR-pQCT).

Methods: Testosterone for Bone (T4Bone) is a sub-study of the Testosterone for the Prevention of Diabetes Mellitus (T4DM), a 2-year randomised placebo-controlled multicentre trial of injectable T undecanoate (TU) in men aged >50 years at high risk of diabetes.

Interventions: TU or placebo injections 3-monthly over 2 years on the background of a lifestyle program.

Main outcomes: Primary endpoint was cortical volumetric BMD (vBMD) at the distal tibia in 177 men in one centre. Secondary endpoints including other HR-pQCT parameters and bone remodelling markers. Areal BMD (aBMD) was measured by dual energy X-ray absorptiometry (DXA) in 601 men in five centres. Using a linear mixed model for repeated measures, the treatment effects were defined as mean adjusted differences (MAD [95% CI] over 2 years between groups.

Results: Baseline age was 60.2years, BMI 35.4kg/m2 and total T 14.2nmol/L. At the tibia, T treatment increased cortical vBMD by 9.33mgHA/cm3 [3.96;14.71], p<0.001 or 3.1% [1.2;5.0],  total vBMD by 4.16mgHA/cm3 [2.14;6.19], p<0.001 or 1.3% [0.6;1.9]). T treatment also increased cortical area and thickness but effects on trabecular architecture were minor. Results at the radius were similar. T treatment reduced CTX -48.1ng/L [-81.1;-15.1] p<0.001 and P1NP -6.8mg/L [-10.9;-2.7], p<0.001). T treatment increased aBMD at the lumbar spine (0.04g/cm2 [0.03;0.05], p<0.001 or 3.3% [2.7;3.9]), and the total hip (0.01g/cm2 [0.01;0.02], p<0.001 or 1.9% [1.2;2.7]). The treatment effect was not dependent on baseline T or oestradiol.

Conclusion: In men, T treatment for 2 years increased volumetric bone density, predominantly via effects on cortical bone. The implications for fracture risk reduction require further study.