Effect of testosterone treatment on volumetric bone density and strength in older men with low testosterone a controlled clinical trial

Peter J. Snyder, David L. Kopperdahl, Alisa J. Stephens-Shields, Susan S. Ellenberg, Jane A. Cauley, Kristine E. Ensrud, Cora E. Lewis, Elizabeth Barrett-Connor, Ann V. Schwartz, David C. Lee, Shalender Bhasin, Glenn R. Cunningham, Thomas M. Gill, Alvin M. Matsumoto, Ronald S. Swerdloff, Shehzad Basaria, Susan J. Diem, Christina Wan, Xiaoling Hou, Denise CifelliDarlene Dougar, Bret Zeldow, Douglas C. Bauer, Tony M. Keaveny

Research output: Contribution to journalArticlepeer-review

236 Scopus citations


IMPORTANCE As men age, they experience decreased serum testosterone concentrations, decreased bone mineral density (BMD), and increased risk of fracture. OBJECTIVE To determine whether testosterone treatment of older men with low testosterone increases volumetric BMD (vBMD) and estimated bone strength. DESIGN, SETTING, AND PARTICIPANTS Placebo-controlled, double-blind trial with treatment allocation by minimization at 9 US academic medical centers of men 65 years or older with 2 testosterone concentrations averaging less than 275 ng/L participating in the Testosterone Trials from December 2011 to June 2014. The analysis was a modified intent-to-treat comparison of treatment groups by multivariable linear regression adjusted for balancing factors as required by minimization. INTERVENTIONS Testosterone gel, adjusted to maintain the testosterone level within the normal range for young men, or placebo gel for 1 year. MAIN OUTCOMES AND MEASURES Spine and hip vBMDwas determined by quantitative computed tomography at baseline and 12 months. Bone strength was estimated by finite element analysis of quantitative computed tomography data. Areal BMD was assessed by dual energy x-ray absorptiometry at baseline and 12 months. RESULTS There were 211 participants (mean [SD] age, 72.3 [5.9] years; 86%white; mean [SD] body mass index, 31.2 [3.4]). Testosterone treatment was associated with significantly greater increases than placebo in mean spine trabecular vBMD (7.5%; 95%CI, 4.8%to 10.3% vs 0.8%; 95%CI, -1.9%to 3.4%; treatment effect, 6.8%; 95%CI, 4.8%-8.7%; P < .001), spine peripheral vBMD, hip trabecular and peripheral vBMD, and mean estimated strength of spine trabecular bone (10.8%; 95%CI, 7.4%to 14.3%vs 2.4%; 95%CI, -1.0%to 5.7%; treatment effect, 8.5%; 95%CI, 6.0%-10.9%; P< .001), spine peripheral bone, and hip trabecular and peripheral bone. The estimated strength increases were greater in trabecular than peripheral bone and greater in the spine than hip. Testosterone treatment increased spine areal BMD but less than vBMD. CONCLUSIONS AND RELEVANCE Testosterone treatment for 1 year of older men with low testosterone significantly increased vBMD and estimated bone strength, more in trabecular than peripheral bone and more in the spine than hip. A larger, longer trial could determine whether this treatment also reduces fracture risk.

Original languageEnglish (US)
Pages (from-to)471-479
Number of pages9
JournalJAMA internal medicine
Issue number4
StatePublished - Apr 1 2017

Bibliographical note

Publisher Copyright:
© 2017 American Medical Association.


Dive into the research topics of 'Effect of testosterone treatment on volumetric bone density and strength in older men with low testosterone a controlled clinical trial'. Together they form a unique fingerprint.

Cite this