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Original Investigation
February 21, 2017

Effect of Testosterone Treatment on Volumetric Bone Density and Strength in Older Men With Low Testosterone: A Controlled Clinical Trial

Author Affiliations
  • 1Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia
  • 2O.N. Diagnostics, LLC, Berkeley, California
  • 3Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia
  • 4Department of Epidemiology, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, Pennsylvania
  • 5Division of Epidemiology and Community Health, Department of Medicine, University of Minnesota, Minneapolis
  • 6Minneapolis VA Health Care System, Minneapolis
  • 7Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham
  • 8Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego, School of Medicine, La Jolla
  • 9Department of Epidemiology and Biostatistics, University of California, San Francisco
  • 10Research Program in Men’s Health: Aging and Metabolism, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 11Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, Texas
  • 12Baylor St. Luke’s Medical Center, Houston, Texas
  • 13Division of Geriatric Medicine, Yale School of Medicine, New Haven, Connecticut
  • 14Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Puget Sound Health Care System, University of Washington School of Medicine, Seattle
  • 15Division of Gerontology and Geriatric Medicine, Department of Internal Medicine, University of Washington School of Medicine, Seattle
  • 16Division of Endocrinology, Harbor–University of California at Los Angeles Medical Center, Torrance
  • 17Los Angeles Biomedical Research Institute, Torrance, California
  • 18Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia
  • 19Department of Medicine, University of California, San Francisco
  • 20Department of Epidemiology and Biostatistics, University of California, San Francisco
  • 21Departments of Mechanical Engineering and Bioengineering, University of California, Berkeley
JAMA Intern Med. 2017;177(4):471-479. doi:10.1001/jamainternmed.2016.9539
Key Points

Question  Will testosterone treatment of older men with low testosterone improve their bone density and strength?

Findings  Testosterone treatment of older men with low testosterone increased volumetric trabecular bone mineral density of the lumbar spine and estimated bone strength significantly compared with placebo.

Meaning  These results suggest that a larger and longer trial to determine whether testosterone treatment decreases fracture risk in this population is warranted.

Abstract

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 vBMD was 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.

Trial Registration  clinicaltrials.gov Identifier: NCT00799617

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