Mark Ng Tang Fui1,2, Rudolf Hoermann1, Karen Bracken3, David J Handelsman4, Warrick J Inder5, Bronwyn G A Stuckey6, Bu B Yeap7, Ali Ghasem-Zadeh1, Kristy P Robledo3, David Jesudason8, Jeffrey D Zajac1,2, Gary A Wittert8, Mathis Grossmann1,2. 1. Department of Medicine (Austin Health), The University of Melbourne, Victoria, 3084, Australia. 2. Department of Endocrinology, Austin Health, Heidelberg, Victoria, 3084, Australia. 3. NHMRC Clinical Trials Centre, University of Sydney, New South Wales, 2050, Australia. 4. ANZAC Research Institute, University of Sydney and Department of Andrology, Concord Hospital, Sydney New South Wales, 2139, Australia. 5. Princess Alexandra Hospital and the University of Queensland, Queensland, 4102, Australia. 6. Keogh Institute for Medical Research, Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital and University of Western Australia, Western Australia, 6009, Australia. 7. Medical School, University of Western Australia and Department of Endocrinology and Diabetes, Freemantle & Fiona Stanley Hospital, Perth, Western Australia, 6150, Australia. 8. Freemasons Foundation Centre for Men's Health, University of Adelaide, Adelaide, South Australia, Australia, and The Queen Elizabeth Hospital, South Australia, 5000, Australia.
Abstract
CONTEXT: Testosterone treatment increases bone mineral density (BMD) in hypogonadal men. Effects on bone microarchitecture, a determinant of fracture risk, are unknown. OBJECTIVE: We aimed to determine the effect of testosterone treatment on bone microarchitecture using high resolution-peripheral quantitative computed tomography (HR-pQCT). METHODS:Men ≥50 years of age were recruited from 6 Australian centers and were randomized to receive injectable testosterone undecanoate or placebo over 2 years on the background of a community-based lifestyle program. The primary endpoint was cortical volumetric BMD (vBMD) at the distal tibia, measured using HR-pQCT in 177 men (1 center). Secondary endpoints included other HR-pQCT parameters and bone remodeling markers. Areal BMD (aBMD) was measured by dual-energy x-ray absorptiometry (DXA) in 601 men (5 centers). Using a linear mixed model for repeated measures, the mean adjusted differences (95% CI) at 12 and 24 months between groups are reported as treatment effect. RESULTS: Over 24 months, testosterone treatment, versus placebo, increased tibial cortical vBMD, 9.33 mg hydroxyapatite (HA)/cm3) (3.96, 14.71), P < 0.001 or 3.1% (1.2, 5.0); radial cortical vBMD, 8.96 mg HA/cm3 (3.30, 14.62), P = 0.005 or 2.9% (1.0, 4.9); total tibial vBMD, 4.16 mg HA/cm3 (2.14, 6.19), P < 0.001 or 1.3% (0.6, 1.9); and total radial vBMD, 4.42 mg HA/cm3 (1.67, 7.16), P = 0.002 or 1.8% (0.4, 2.0). Testosterone also significantly increased cortical area and thickness at both sites. Effects on trabecular architecture were minor. Testosterone reduced bone remodeling markers CTX, -48.1 ng/L [-81.1, -15.1], P < 0.001 and P1NP, -6.8 μg/L[-10.9, -2.7], P < 0.001. Testosterone significantly increased aBMD at the lumbar spine, 0.04 g/cm2 (0.03, 0.05), P < 0.001 and the total hip, 0.01 g/cm2 (0.01, 0.02), P < 0.001. CONCLUSION: In men ≥ 50 years of age, testosterone treatment for 2 years increased volumetric bone density, predominantly via effects on cortical bone. Implications for fracture risk reduction require further study.
RCT Entities:
CONTEXT: Testosterone treatment increases bone mineral density (BMD) in hypogonadal men. Effects on bone microarchitecture, a determinant of fracture risk, are unknown. OBJECTIVE: We aimed to determine the effect of testosterone treatment on bone microarchitecture using high resolution-peripheral quantitative computed tomography (HR-pQCT). METHODS:Men ≥ 50 years of age were recruited from 6 Australian centers and were randomized to receive injectable testosterone undecanoate or placebo over 2 years on the background of a community-based lifestyle program. The primary endpoint was cortical volumetric BMD (vBMD) at the distal tibia, measured using HR-pQCT in 177 men (1 center). Secondary endpoints included other HR-pQCT parameters and bone remodeling markers. Areal BMD (aBMD) was measured by dual-energy x-ray absorptiometry (DXA) in 601 men (5 centers). Using a linear mixed model for repeated measures, the mean adjusted differences (95% CI) at 12 and 24 months between groups are reported as treatment effect. RESULTS: Over 24 months, testosterone treatment, versus placebo, increased tibial cortical vBMD, 9.33 mg hydroxyapatite (HA)/cm3) (3.96, 14.71), P < 0.001 or 3.1% (1.2, 5.0); radial cortical vBMD, 8.96 mg HA/cm3 (3.30, 14.62), P = 0.005 or 2.9% (1.0, 4.9); total tibial vBMD, 4.16 mg HA/cm3 (2.14, 6.19), P < 0.001 or 1.3% (0.6, 1.9); and total radial vBMD, 4.42 mg HA/cm3 (1.67, 7.16), P = 0.002 or 1.8% (0.4, 2.0). Testosterone also significantly increased cortical area and thickness at both sites. Effects on trabecular architecture were minor. Testosterone reduced bone remodeling markers CTX, -48.1 ng/L [-81.1, -15.1], P < 0.001 and P1NP, -6.8 μg/L[-10.9, -2.7], P < 0.001. Testosterone significantly increased aBMD at the lumbar spine, 0.04 g/cm2 (0.03, 0.05), P < 0.001 and the total hip, 0.01 g/cm2 (0.01, 0.02), P < 0.001. CONCLUSION: In men ≥ 50 years of age, testosterone treatment for 2 years increased volumetric bone density, predominantly via effects on cortical bone. Implications for fracture risk reduction require further study.
Authors: G Corona; W Vena; A Pizzocaro; V A Giagulli; D Francomano; G Rastrelli; G Mazziotti; A Aversa; A M Isidori; R Pivonello; L Vignozzi; E Mannucci; M Maggi; A Ferlin Journal: J Endocrinol Invest Date: 2022-01-18 Impact factor: 4.256
Authors: A M Isidori; A Aversa; A Calogero; A Ferlin; S Francavilla; F Lanfranco; R Pivonello; V Rochira; G Corona; M Maggi Journal: J Endocrinol Invest Date: 2022-08-26 Impact factor: 5.467