Effect of Testosterone treatment on bone microarchitecture and bone mineral density in men: a two-year RCT

Abstract

CONTEXT: Testosterone treatment increases bone mineral density (BMD) in hypogonadal men. Effects on bone microarchitecture, a determinant of fracture risk, are unknown. OBJECTIVE: Determine the effect of testosterone treatment on bone microarchitecture using high resolution-peripheral quantitative computed tomography (HR-pQCT). DESIGN, SETTING, PARTICIPANTS: Men>50 years were recruited from six Australian centres. INTERVENTIONS: Injectable testosterone undecanoate or placebo over 2 years on the background of a community-based lifestyle program. MAIN OUTCOMES: Primary endpoint was cortical volumetric BMD (vBMD) at the distal tibia, measured using HR-pQCT in 177 men (one centre). Secondary endpoints included other HR-pQCT parameters and bone remodelling markers. Areal BMD (aBMD) was measured by dual energy X-ray absorptiometry (DXA) in 601 men (five centres). Using a linear mixed model for repeated measures, the mean adjusted differences (MAD) [95% CI] at 12 and 24 months between groups are reported as treatment effect. RESULTS: Over 24 months, testosterone treatment, compared to placebo, increased tibial cortical vBMD), 9.33mgHA/cm 3[3.96;14.71],p<0.001 or 3.1%[1.2;5.0], radial cortical vBMD, 8.96mgHA/cm 3[3.30;14.62],p=0.005 or 2.9%[1.0;4.9], total tibial vBMD, 4.16mgHA/cm 3[2.14;6.19],p<0.001 or 1.3%[0.6;1.9] and total radial vBMD, 4.42mgHA/cm 3[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, -48.1ng/L[-81.1;-15.1],p<0.001, and P1NP, -6.8μg/L[-10.9;-2.7], p<0.001. Testosterone significantly increased aBMD at the lumbar spine, 0.04 g/cm 2[0.03;0.05],p<0.001, and the total hip, 0.01g/cm 2[0.01;0.02],p<0.001. CONCLUSIONS: In men>50 years, testosterone treatment for 2 years increased volumetric bone density, predominantly via effects on cortical bone. Implications for fracture risk reduction require further study.