Further reductions in nonvertebral fracture rate with long-term denosumab treatment in the FREEDOM open-label extension and influence of hip bone mineral density after 3 years.

Limited data exist on the efficacy of long-term therapies
for osteoporosis. In osteoporotic postmenopausal women
receiving denosumab for 7 years, nonvertebral fracture
rates significantly decreased in years 4–7 versus years 1–3.
This is the first demonstration of a further benefit on fracture
outcomes with long-term therapy for osteoporosis.
Introduction This study aimed to evaluate whether
denosumab treatment continued beyond 3 years is associated
with a further reduction in nonvertebral fracture rates.
Methods Participants who completed the 3-year placebocontrolled
Fracture REduction Evaluation of Denosumab in
Osteoporosis every 6 Months (FREEDOM) study were invited
to participate in an open-label extension. The present analysis
includes 4,074 postmenopausal women with osteoporosis
(n=2,343 long-term; n=1,731 cross-over) who enrolled in the
extension, missed ≤1 dose during their first 3 years of
denosumab treatment, and continued into the fourth year of
treatment. Comparison of nonvertebral fracture rates during
years 1–3 of denosumab with that of the fourth year and with
the rate during years 4–7 was evaluated.
Results For the combined group, the nonvertebral fracture rate
per 100 participant-years was 2.15 for the first 3 years of
denosumab treatment (referent) and 1.36 in the fourth year
(rate ratio [RR]=0.64; 95 % confidence interval (CI)=0.48
to 0.85, p=0.003). Comparable findings were observed in
the groups separately and when nonvertebral fracture rates
during years 1–3 were compared to years 4–7 in the longterm
group (RR=0.79; 95 % CI=0.62 to 1.00, p=0.046).
Fracture rate reductions in year 4 were most prominent in
subjects with persisting low hip bone mineral density (BMD).
Conclusions Denosumab treatment beyond 3 years was associated
with a further reduction in nonvertebral fracture rate
that persisted through 7 years of continuous denosumab administration.
The degree to which denosumab further reduces
nonvertebral fracture risk appears influenced by the hip bone
density achieved with initial therapy