Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2017 Apr 1;177(4):471-479.
doi: 10.1001/jamainternmed.2016.9539.

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

Affiliations
Free PMC article
Randomized Controlled Trial

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

Peter J Snyder et al. JAMA Intern Med. .
Free PMC article

Erratum in

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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Snyder reports grants from the National Institute on Aging (NIA), National Institutes of Health (NIH), grants and nonfinancial support from AbbVie (formerly Solvay and Abbott Laboratories), during the conduct of the study; 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 from NIA and NIH, grants and other from AbbVie (formerly Solvay & Abbott Lab), during the conduct of the study. Dr Ellenberg reports grants from NIH and AbbVie, Inc, during the conduct of the study; grants from AbbVie, Inc, outside the submitted work. Dr Ensrud reports grants from NIA, during the conduct of the study. Dr Lewis reports grants from NIH and AbbVie, during the conduct of the study. Dr Schwartz reports grants from NIH, during the conduct of the study; 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 from NIA, during the conduct of the study; grants and personal fees from Abbvie, Lilly, and Regeneron, 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; 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 Diem reports grants from NIA, during the conduct of the study. Dr Wang reports grants from Besins Health International, other from Abbvie, during the conduct of the study; grants from Clarus Therapeutics, outside the submitted work. Dr Keaveny reports grants from NIA and NIH, grants and other from AbbVie (formerly Solvay & Abbott Lab), during the conduct of the study.

Figures

Figure 1
Figure 1. Screening and Retention of Participants
Figure 2
Figure 2. Median Serum Concentrations of Total Testosterone, Free Testosterone, and Estradiol From Months 0 to 12 in Men Treated With Testosterone or Placebo
The P values indicate the significance of the difference in serum concentrations in men in the testosterone arm compared with men in the placebo arm. The shaded areas represent the normal ranges for healthy young men. Error bars indicate interquartile ranges. SI conversion factors: To convert testosterone to nanomoles per liter, multiply by 0.0347; to convert free testosterone to picomoles per liter, multiply by 3.47; to convert estradiol to picomoles per liter, multiply by 3.67.
Figure 3
Figure 3. Effects of Testosterone or Placebo Treatment for 12 Months on Volumetric Bone Mineral Density and Estimated Bone Strength of Trabecular, Peripheral, and Whole Bone of the Spine and Hip, as Assessed by Quantitative Computed Tomography
Bars indicate means, and error bars, standard deviations. The P values indicate the significance of the difference in change in percent volumetric bone mineral density or estimated strength from baseline to 12 months for men in the testosterone arm compared with the placebo arm.

Comment in

Similar articles

  • Association of Testosterone Levels With Anemia in Older Men: A Controlled Clinical Trial.
    Roy CN, Snyder PJ, Stephens-Shields AJ, Artz AS, Bhasin S, Cohen HJ, Farrar JT, Gill TM, Zeldow B, Cella D, Barrett-Connor E, Cauley JA, Crandall JP, Cunningham GR, Ensrud KE, Lewis CE, Matsumoto AM, Molitch ME, Pahor M, Swerdloff RS, Cifelli D, Hou X, Resnick SM, Walston JD, Anton S, Basaria S, Diem SJ, Wang C, Schrier SL, Ellenberg SS. Roy CN, et al. JAMA Intern Med. 2017 Apr 1;177(4):480-490. doi: 10.1001/jamainternmed.2016.9540. JAMA Intern Med. 2017. PMID: 28241237 Free PMC article. Clinical Trial.
  • Areal and volumetric bone mineral density and risk of multiple types of fracture in older men.
    Chalhoub D, Orwoll ES, Cawthon PM, Ensrud KE, Boudreau R, Greenspan S, Newman AB, Zmuda J, Bauer D, Cummings S, Cauley JA; Osteoporotic Fractures in Men (MrOS) Study Research Group. Chalhoub D, et al. Bone. 2016 Nov;92:100-106. doi: 10.1016/j.bone.2016.08.014. Epub 2016 Aug 20. Bone. 2016. PMID: 27554426 Free PMC article. Clinical Trial.
  • Bone density, turnover, and estimated strength in postmenopausal women treated with odanacatib: a randomized trial.
    Brixen K, Chapurlat R, Cheung AM, Keaveny TM, Fuerst T, Engelke K, Recker R, Dardzinski B, Verbruggen N, Ather S, Rosenberg E, de Papp AE. Brixen K, et al. J Clin Endocrinol Metab. 2013 Feb;98(2):571-80. doi: 10.1210/jc.2012-2972. Epub 2013 Jan 21. J Clin Endocrinol Metab. 2013. PMID: 23337728 Clinical Trial.
  • The structural basis of bone fragility in men.
    Seeman E. Seeman E. Bone. 1999 Jul;25(1):143-7. doi: 10.1016/s8756-3282(99)00117-9. Bone. 1999. PMID: 10423041 Review.
  • Trabecular Bone Score: Where are we now?
    Bousson V, Bergot C, Sutter B, Thomas T, Bendavid S, Benhamou CL, Blain H, Brazier M, Breuil V, Briot K, Chapurlat R, Chapuis L, Cohen Solal M, Fardellone P, Feron JM, Gauvain JB, Laroche M, Legrand E, Lespessailles E, Linglart A, Marcelli C, Roux C, Souberbielle JC, Tremollieres F, Weryha G, Cortet B; Groupe de Recherche et d’Information sur les Ostéoporoses (GRIO). Bousson V, et al. Joint Bone Spine. 2015 Oct;82(5):320-5. doi: 10.1016/j.jbspin.2015.02.005. Epub 2015 Apr 24. Joint Bone Spine. 2015. PMID: 25921803 Review.
See all similar articles

Cited by 29 articles

See all "Cited by" articles

Publication types

MeSH terms

Associated data

Feedback