The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study.

Summary: The FREEDOM study and its Extension provide
long-term information about the effects of denosumab for
the treatment of postmenopausal osteoporosis. Treatment for
up to 8 years was associated with persistent reduction of bone
turnover, continued increases in bone mineral density, low
fracture incidence, and a favorable benefit/risk profile.
Introduction: This study aims to report the results through year
5 of the FREEDOM Extension study, representing up to
8 years of continued denosumab treatment in postmenopausal
women with osteoporosis.
Methods : Women who completed the 3-year FREEDOM
study were eligible to enter the 7-year open-label
FREEDOM Extension in which all participants are scheduled
to receive denosumab, since placebo assignment was
discontinued for ethical reasons. A total of 4550 women enrolled
in the Extension (2343 long-term; 2207 cross-over). In
this analysis, women in the long-term and cross-over groups
received denosumab for up to 8 and 5 years, respectively.
Results Throughout the Extension, sustained reduction of
bone turnover markers (BTMs) was observed in both
groups. In the long-term group, mean bone mineral density
(BMD) continued to increase significantly at each
time point measured, for cumulative 8-year gains of 18.4
and 8.3 % at the lumbar spine and total hip, respectively.
In the cross-over group, mean BMD increased significantly
from the Extension baseline for 5-year cumulative
gains of 13.1 and 6.2 % at the lumbar spine and total
hip, respectively. The yearly incidence of new vertebral
and nonvertebral fractures remained low in both groups.
The incidence of adverse and serious adverse events did
not increase over time. Through Extension year 5, eight
events of osteonecrosis of the jaw and two events of atypical
femoral fracture were confirmed.