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.
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, doubleblind 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 <or= -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 <or= 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.
Brown
Jacques P
JP
Laval University, Le Centre Hospitalier Universitaire de Québec, Quebec City, Québec, Canada. jacques.brown@crchul.ulaval.ca
Prince
Richard L
RL
Deal
Chad
C
Recker
Robert R
RR
Kiel
Douglas P
DP
de Gregorio
Luiz H
LH
Hadji
Peyman
P
Hofbauer
Lorenz C
LC
Alvaro-Gracia
Jose M
JM
Wang
Huei
H
Austin
Matthew
M
Wagman
Rachel B
RB
Newmark
Richard
R
Libanati
Cesar
C
San Martin
Javier
J
Bone
Henry G
HG