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


METHODS
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.


METHODS
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.
Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. orwoll@ohsu.edu
Eric
E
Orwoll
Christence S
CS
Teglbjærg
Bente L
BL
Langdahl
Roland
R
Chapurlat
Edward
E
Czerwinski
David L
DL
Kendler
Jean-Yves
JY
Reginster
Alan
A
Kivitz
E Michael
EM
Lewiecki
Paul D
PD
Miller
Michael A
MA
Bolognese
Michael R
MR
McClung
Henry G
HG
Bone
Östen
Ö
Ljunggren
Bo
B
Abrahamsen
Ugis
U
Gruntmanis
Yu-Ching
YC
Yang
Rachel B
RB
Wagman
Suresh
S
Siddhanti
Andreas
A
Grauer
Jesse W
JW
Hall
Steven
S
Boonen
D015502:Absorptiometry, Photon; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000378:metabolism; D000069448:Denosumab; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D013739:Testosterone / Q000097:blood
D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D013739:Testosterone; D000069448:Denosumab