Testosterone Increases Lumbar Spine Volumetric Trabecular BMD in Older Men

This article originally appeared here.
Testosterone treatment improved both bone mineral density and strength in older men.
Testosterone treatment improved both 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.

High-Yield Data Summary

  • Testosterone treatment in men significantly increased volumetric BMD and estimated bone strength. Further study is needed to determine if it will lead to decreased fracture risk.

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 

 "The clinical significance of the effect of testosterone treatment on vBMD and estimated bone strength in these men will depend on whether testosterone treatment also reduces fracture risk. Some evidence suggests that it might," the researchers wrote.  

"Bone strength, as estimated by FEA of QCT data, does correlate well with physical strength of human vertebrae and is associated with prevalent bone fractures and incident spine and hip fractures."

Study Limitations

  • Results only apply to the particular population of men with low serum testosterone levels, not men with osteoporosis.


Disclosures

Dr Snyder reports grants and nonfinancial support from AbbVie during the conduct of the study and personal fees from Watson Laboratories outside the submitted work. Dr Kopperdahl is an employee of and has equity interest in O.N. Diagnostics. Dr Stephens-Shields reports grants and other support from AbbVie during the conduct of the study. Dr Ellenberg reports grants from AbbVie Inc during the conduct of the study and grants from AbbVie Inc outside the submitted work. Dr Lewis reports grants from AbbVie during the conduct of the study. Dr Schwartz reports personal fees from Amgen, Janssen Pharmaceutical, and Merck, and personal fees and nonfinancial support from Chugai Pharmaceutical outside the submitted work. Dr Lee is an employee of and has equity interest in O.N. Diagnostics. Dr Bhasin reports grants and personal fees from AbbVie, Lilly, and Regenerom and grants from Transition Therapeutics outside the submitted work. In addition, Dr Bhasin has a patent-free testosterone calculator pending and has equity interest in FPT, LLC. Dr Cunningham reports personal fees from AbbVie, Apricus, Besins, Clarus Therapeutics, Endo Pharma, Ferring, Lilly, Pfizer, and Repros Therapeutics, outside the submitted work. Dr Matsumoto reports personal fees from AbbVie, Endo, Lilly, Lipocine, and Clarus outside the submitted work. Dr Swerdloff reports grants from the Bone Trial of the Testosterone Trials during the conduct of the study and grants and other from Clarus and Antares and grants from Lipesene outside the submitted work. Dr Basaria reports other from Eli Lilly and Takeda Pharmaceuticals outside the submitted work. Dr Wang reports grants from Besins Health International and other support from AbbVie during the conduct of the study and grants from Clarus Therapeutics outside the submitted work. Dr Keaveny reports grants and other support from AbbVie during the conduct of the study.

References

  1. Snyder PJ, Kopperdahl DL, Stephens-Shields AJ, Ellenberg SS, et al. Effect of testosterone treatment on volumetric bone density and strength in older men with low testosterone [published online February 21, 2017]. JAMA Intern Med. doi: 10.1001/jamainternmed.2016.9539

  2. Snyder PJ, Ellenberg SS, Cunningham GR, et al. The testosterone trials: seven coordinated trials of testosterone treatment in elderly men [published online March 31, 2014]. Clin Trials. doi: 10.1177/1740774514524032

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