A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density

Eric Orwoll, Christence S. Teglbjærg, Bente L. Langdahl, Roland Chapurlat, Edward Czerwinski, David L. Kendler, Jean Yves Reginster, Alan Kivitz, E. Michael Lewiecki, Paul D. Miller, Michael A. Bolognese, Michael R. McClung, Henry G. Bone, Östen Ljunggren, Bo Abrahamsen, Ugis Gruntmanis, Yu Ching Yang, Rachel B. Wagman, Suresh Siddhanti, Andreas GrauerJesse W. Hall, Steven Boonen

Research output: Contribution to journalArticle

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Abstract

Context: Men with low bone mineral density (BMD) were treated with denosumab. Objective: Our objective was to investigate the effects of denosumab compared with placebo in men with low BMD after 1 yr of treatment. Design, Subjects, and Intervention: This was a placebo-controlled, phase 3 study to investigate the efficacy and safety of denosumab 60 mg every 6 months vs. placebo in men with low BMD. Main Outcome Measure: The primary endpoint was the percent change from baseline in lumbar spine (LS) BMD at month 12. Results: Of the 242 randomized subjects (mean age 65 yr), 228 (94.2%) completed 1 yr of denosumab therapy. After 12 months, denosumab resulted in BMD increases of 5.7% at the LS, 2.4% at the total hip, 2.1% at the femoral neck, 3.1% at the trochanter, and 0.6% at the one third radius (adjusted P≥0.0144 for BMD percent differences at all sites compared with placebo). Sensitivity analyses done by controlling for baseline covariates (such as baseline testosterone levels, BMD T-scores, and 10-yr osteoporotic fracture risk) demonstrated that the results of the primary endpoint were robust. Subgroup analyses indicate that treatment with denosumab was effective across a spectrum of clinical situations. Treatment with denosumab significantly reduced serum CTX levels at d 15 (adjusted P < 0.0001). The incidence of adverse events was similar between groups. Conclusions: One year of denosumab therapy in men with low BMD was well tolerated and resulted in a reduction in bone resorption and significant increases in BMD at all skeletal sites assessed.

Original languageEnglish (US)
Pages (from-to)3161-3169
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume97
Issue number9
DOIs
StatePublished - Sep 2012

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Bone Density
Minerals
Bone
Placebos
Therapeutics
Spine
Denosumab
Osteoporotic Fractures
Femur Neck
Bone Resorption
Femur
Testosterone
Hip
Outcome Assessment (Health Care)
Safety
Incidence
Serum

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Orwoll, E., Teglbjærg, C. S., Langdahl, B. L., Chapurlat, R., Czerwinski, E., Kendler, D. L., ... Boonen, S. (2012). A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. Journal of Clinical Endocrinology and Metabolism, 97(9), 3161-3169. https://doi.org/10.1210/jc.2012-1569

A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. / Orwoll, Eric; Teglbjærg, Christence S.; Langdahl, Bente L.; Chapurlat, Roland; Czerwinski, Edward; Kendler, David L.; Reginster, Jean Yves; Kivitz, Alan; Lewiecki, E. Michael; Miller, Paul D.; Bolognese, Michael A.; McClung, Michael R.; Bone, Henry G.; Ljunggren, Östen; Abrahamsen, Bo; Gruntmanis, Ugis; Yang, Yu Ching; Wagman, Rachel B.; Siddhanti, Suresh; Grauer, Andreas; Hall, Jesse W.; Boonen, Steven.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 97, No. 9, 09.2012, p. 3161-3169.

Research output: Contribution to journalArticle

Orwoll, E, Teglbjærg, CS, Langdahl, BL, Chapurlat, R, Czerwinski, E, Kendler, DL, Reginster, JY, Kivitz, A, Lewiecki, EM, Miller, PD, Bolognese, MA, McClung, MR, Bone, HG, Ljunggren, Ö, Abrahamsen, B, Gruntmanis, U, Yang, YC, Wagman, RB, Siddhanti, S, Grauer, A, Hall, JW & Boonen, S 2012, 'A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density', Journal of Clinical Endocrinology and Metabolism, vol. 97, no. 9, pp. 3161-3169. https://doi.org/10.1210/jc.2012-1569
Orwoll, Eric ; Teglbjærg, Christence S. ; Langdahl, Bente L. ; Chapurlat, Roland ; Czerwinski, Edward ; Kendler, David L. ; Reginster, Jean Yves ; Kivitz, Alan ; Lewiecki, E. Michael ; Miller, Paul D. ; Bolognese, Michael A. ; McClung, Michael R. ; Bone, Henry G. ; Ljunggren, Östen ; Abrahamsen, Bo ; Gruntmanis, Ugis ; Yang, Yu Ching ; Wagman, Rachel B. ; Siddhanti, Suresh ; Grauer, Andreas ; Hall, Jesse W. ; Boonen, Steven. / A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. In: Journal of Clinical Endocrinology and Metabolism. 2012 ; Vol. 97, No. 9. pp. 3161-3169.
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T1 - A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density

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AU - Teglbjærg, Christence S.

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AU - Chapurlat, Roland

AU - Czerwinski, Edward

AU - Kendler, David L.

AU - Reginster, Jean Yves

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AU - Miller, Paul D.

AU - Bolognese, Michael A.

AU - McClung, Michael R.

AU - Bone, Henry G.

AU - Ljunggren, Östen

AU - Abrahamsen, Bo

AU - Gruntmanis, Ugis

AU - Yang, Yu Ching

AU - Wagman, Rachel B.

AU - Siddhanti, Suresh

AU - Grauer, Andreas

AU - Hall, Jesse W.

AU - Boonen, Steven

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N2 - Context: Men with low bone mineral density (BMD) were treated with denosumab. Objective: Our objective was to investigate the effects of denosumab compared with placebo in men with low BMD after 1 yr of treatment. Design, Subjects, and Intervention: This was a placebo-controlled, phase 3 study to investigate the efficacy and safety of denosumab 60 mg every 6 months vs. placebo in men with low BMD. Main Outcome Measure: The primary endpoint was the percent change from baseline in lumbar spine (LS) BMD at month 12. Results: Of the 242 randomized subjects (mean age 65 yr), 228 (94.2%) completed 1 yr of denosumab therapy. After 12 months, denosumab resulted in BMD increases of 5.7% at the LS, 2.4% at the total hip, 2.1% at the femoral neck, 3.1% at the trochanter, and 0.6% at the one third radius (adjusted P≥0.0144 for BMD percent differences at all sites compared with placebo). Sensitivity analyses done by controlling for baseline covariates (such as baseline testosterone levels, BMD T-scores, and 10-yr osteoporotic fracture risk) demonstrated that the results of the primary endpoint were robust. Subgroup analyses indicate that treatment with denosumab was effective across a spectrum of clinical situations. Treatment with denosumab significantly reduced serum CTX levels at d 15 (adjusted P < 0.0001). The incidence of adverse events was similar between groups. Conclusions: One year of denosumab therapy in men with low BMD was well tolerated and resulted in a reduction in bone resorption and significant increases in BMD at all skeletal sites assessed.

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