Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass

A randomized, blinded, phase 3 trial

Jacques P. Brown, Richard L. Prince, Chad Deal, Robert R. Recker, Douglas P. Kiel, Luiz H. De Gregorio, Peyman Hadji, Lorenz C. Hofbauer, Jose M. Álvaro-Gracia, Huei Wang, Matthew Austin, Rachel B. Wagman, Richard Newmark, Cesar Libanati, Javier San Martin, Henry G. Bone

Research output: Contribution to journalArticle

385 Citations (Scopus)

Abstract

Denosumab is a fully human monoclonal antibody that inhibits bone resorption by neutralizing RANKL, a key mediator of osteoclast formation, function, and survival. This phase 3, multicenter, double-blind study compared the efficacy and safety of denosumab with alendronate in postmenopausal women with low bone mass. One thousand one hundred eighty-nine postmenopausal women with a T-score ≤ -2.0 at the lumbar spine or total hip were randomized 1:1 to receive subcutaneous denosumab injections (60 mg every 6 mo [Q6M]) plus oral placebo weekly (n = 594) or oral alendronate weekly (70 mg) plus subcutaneous placebo injections Q6M (n = 595). Changes in BMD were assessed at the total hip, femoral neck, trochanter, lumbar spine, and one-third radius at 6 and 12 mo and in bone turnover markers at months 1, 3, 6, 9, and 12. Safety was evaluated by monitoring adverse events and laboratory values. At the total hip. denosumab significantly increased BMD compared with alendronate at month 12 (3.5% versus 2.6%; p <0.0001). Furthermore, significantly greater increases in BMD were observed with denosumab treatment at all measured skeletal sites (12-mo treatment difference: 0.6%, femoral neck; 1.0%, trochanter; 1.1%, lumbar spine; 0.6%, one-third radius; p ≤ 0.0002 all sites). Denosumab treatment led to significantly greater reduction of bone turnover markers compared with alendronate therapy. Adverse events and laboratory values were similar for denosumab- and alendronate-treated subjects. Denosumab showed significantly larger gains in BMD and greater reduction in bone turnover markers compared with alendronate. The overall safety profile was similar for both treatments.

Original languageEnglish
Pages (from-to)153-161
Number of pages9
JournalJournal of Bone and Mineral Research
Volume24
Issue number1
DOIs
StatePublished - Jan 2009

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Alendronate
Bone Remodeling
Biomarkers
Bone and Bones
Hip
Spine
Femur Neck
Subcutaneous Injections
Safety
Femur
Placebos
Therapeutics
Denosumab
Osteoclasts
Bone Resorption
Double-Blind Method
Monoclonal Antibodies
Survival

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass : A randomized, blinded, phase 3 trial. / Brown, Jacques P.; Prince, Richard L.; Deal, Chad; Recker, Robert R.; Kiel, Douglas P.; De Gregorio, Luiz H.; Hadji, Peyman; Hofbauer, Lorenz C.; Álvaro-Gracia, Jose M.; Wang, Huei; Austin, Matthew; Wagman, Rachel B.; Newmark, Richard; Libanati, Cesar; San Martin, Javier; Bone, Henry G.

In: Journal of Bone and Mineral Research, Vol. 24, No. 1, 01.2009, p. 153-161.

Research output: Contribution to journalArticle

Brown, JP, Prince, RL, Deal, C, Recker, RR, Kiel, DP, De Gregorio, LH, Hadji, P, Hofbauer, LC, Álvaro-Gracia, JM, Wang, H, Austin, M, Wagman, RB, Newmark, R, Libanati, C, San Martin, J & Bone, HG 2009, 'Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: A randomized, blinded, phase 3 trial', Journal of Bone and Mineral Research, vol. 24, no. 1, pp. 153-161. https://doi.org/10.1359/jbmr.0809010
Brown, Jacques P. ; Prince, Richard L. ; Deal, Chad ; Recker, Robert R. ; Kiel, Douglas P. ; De Gregorio, Luiz H. ; Hadji, Peyman ; Hofbauer, Lorenz C. ; Álvaro-Gracia, Jose M. ; Wang, Huei ; Austin, Matthew ; Wagman, Rachel B. ; Newmark, Richard ; Libanati, Cesar ; San Martin, Javier ; Bone, Henry G. / Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass : A randomized, blinded, phase 3 trial. In: Journal of Bone and Mineral Research. 2009 ; Vol. 24, No. 1. pp. 153-161.
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abstract = "Denosumab is a fully human monoclonal antibody that inhibits bone resorption by neutralizing RANKL, a key mediator of osteoclast formation, function, and survival. This phase 3, multicenter, double-blind study compared the efficacy and safety of denosumab with alendronate in postmenopausal women with low bone mass. One thousand one hundred eighty-nine postmenopausal women with a T-score ≤ -2.0 at the lumbar spine or total hip were randomized 1:1 to receive subcutaneous denosumab injections (60 mg every 6 mo [Q6M]) plus oral placebo weekly (n = 594) or oral alendronate weekly (70 mg) plus subcutaneous placebo injections Q6M (n = 595). Changes in BMD were assessed at the total hip, femoral neck, trochanter, lumbar spine, and one-third radius at 6 and 12 mo and in bone turnover markers at months 1, 3, 6, 9, and 12. Safety was evaluated by monitoring adverse events and laboratory values. At the total hip. denosumab significantly increased BMD compared with alendronate at month 12 (3.5{\%} versus 2.6{\%}; p <0.0001). Furthermore, significantly greater increases in BMD were observed with denosumab treatment at all measured skeletal sites (12-mo treatment difference: 0.6{\%}, femoral neck; 1.0{\%}, trochanter; 1.1{\%}, lumbar spine; 0.6{\%}, one-third radius; p ≤ 0.0002 all sites). Denosumab treatment led to significantly greater reduction of bone turnover markers compared with alendronate therapy. Adverse events and laboratory values were similar for denosumab- and alendronate-treated subjects. Denosumab showed significantly larger gains in BMD and greater reduction in bone turnover markers compared with alendronate. The overall safety profile was similar for both treatments.",
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