Testosterone Treatment Increases Bone Mineral Density and Strength in Older Men

Testosterone treatment in older men with low testosterone concentrations shows a significant increase in volumetric bone mineral density (vBMD) and estimated bone strength, according to a study published in JAMA.

Peter Snyder, MD, from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues led a placebo-controlled, double-blind trial to measure spine and hip vBMD and bone strength after testosterone treatment (Bone Trial).¹ 

The study is linked to the Testosterone Trials (T-Trials), also led by Dr Snyder, in which 7 coordinated trials of testosterone treatment in older men with low testosterone concentrations were completed to determine whether testosterone is “efficacious in improving symptoms and objective measures of age associated conditions.”²

The Bone Trial was conducted at 9 US sites with 211 participants out of 295 eligible Bone Trial participants who enrolled in the T-Trials.

Participants were required to be at least 65 years of age and have evidence of impaired sexual or physical function or vitality and a serum testosterone concentration on 2 morning specimens that was less than 275 ng/dL.

Participants were excluded if testosterone treatment would aggravate preexisting medical conditions; if they were taking medicine that would affect bone, excluding calcium and vitamin D supplements; if they did not have an evaluable lumbar vertebra; or if participants had a dual-energy C-ray absorptiometry T-score at any site of less than −3.0.

Overall, 110 participants were administered the testosterone AndroGel 1% and 101 participants were given the placebo gel 5 g daily for 1 year. Testosterone concentration was measured at months 1, 2, 3, 6, and 9 and adjusted after each measurement to keep within the normal range of young men. Participants were also instructed to take 1 tablet of 600 g elemental calcium and 400 units vitamin D₃ twice a day.

Only 104 of the 110 participants treated with testosterone and 85 of 101 participants treated with the placebo were included in the analysis because of withdrawals or a lack of analyzable final scans. Researchers compared spine and hip vBMD using quantitative computed tomography (QCT), bone strength was found by finite element analysis (FEA) of QCT data, and areal BMD was found by dual-energy X-ray absorptiometry analyzed from the start to the end of the study.

Their findings show that, according to QCT data, testosterone treatment showed significant vBMD improvement compared with placebo, especially in mean spine trabecular vBMD: 

• Mean spine trabecular vBMD: 7.5% (95% CI, 4.8%-10.3%) vs 0.8% (95% CI, −1.9% to 3.4%); treatment effect, 6.8% (95% CI, 4.8%-8.7%; P <.001)
• Mean spine peripheral vBMD: 4.0% (95% CI, 2.9%-5.2%) vs 1.1% (95% CI, 0.0%-2.2%); treatment effect, 2.9% (95% CI, 2.1%-3.7%; P <.001)
• Mean hip trabecular vBMD: 1.6% (95% CI, 0.8%-2.4%) vs 0.1% (95% CI, -0.6% to 0.9%); treatment effect, 1.5% (95% CI, 0.9% to 2.0%; P <.001)
• Mean hip peripheral vBMD: 1.6% (95% CI, 0.9%-2.3%) vs 0.7% (95% CI, −0.0% to 1.4%); treatment effect, 1.0% (95% CI, 0.5%-1.5%; P <.001)

According to the FEA of QCT data, testosterone treatment significantly increased bone strength, especially in mean spine trabecular vBMD:

• Mean spine trabecular vBMD: 10.8% (95% CI, 7.4%-14.3%) vs 2.4% (95% CI, −1.0% to 5.7%); treatment effect, 8.5% (95% CI, 6.0%-10.9%; P <.001)
• Mean spine peripheral vBMD: 7.2% (95% CI, 5.2%-9.2%) vs 1.5% (95% CI, −0.5% to 3.4%); treatment effect, 5.7% (95% CI, 4.3%-7.2%; P <.001)
• Mean hip trabecular vBMD: 1.5% (95% CI, 0.5%-2.5%) vs 0.5% (95% CI, −0.5% to 1.5%); treatment effect, 1.0% (95% CI, 0.3%-1.7%; P <.005)
• Mean hip peripheral vBMD: 1.4% (95% CI, 0.7%-2.0%) vs 0.4% (95% CI, −0.3% to 1.0%); treatment effect, 1.0% (95% CI, 0.5%-1.4%; P <.001)

Summary and Clinical Applicability