Effects of denosumab on bone mineral density and bone turnover in postmenopausal
women transitioning from alendronate therapy.
Author(s): Kendler DL, Roux C, Benhamou CL, Brown JP, Lillestol M, Siddhanti S, Man HS, San
Martin J, Bone HG.
Affiliation(s): Clinical Research Centre, Vancouver, British Columbia, Canada.
kendler@ca.inter.net
Publication date & source: 2010, J Bone Miner Res. , 25(1):72-81
Patients treated with bisphosphonates for osteoporosis may discontinue or require
a switch to other therapies. Denosumab binds to RANKL and is a potent inhibitor
of bone resorption that has been shown to increase bone mineral density (BMD) and
decrease fracture risk in postmenopausal women with osteoporosis. This was a
multicenter, international, randomized, double-blind, double-dummy study in 504
postmenopausal women > or = 55 years of age with a BMD T-score of -2.0 or less
and -4.0 or more who had been receiving alendronate therapy for at least 6
months. Subjects received open-label branded alendronate 70 mg once weekly for 1
month and then were randomly assigned to either continued weekly alendronate
therapy or subcutaneous denosumab 60 mg every 6 months and were followed for 12
months. Changes in BMD and biochemical markers of bone turnover were evaluated.
In subjects transitioning to denosumab, total hip BMD increased by 1.90% at month
12 compared with a 1.05% increase in subjects continuing on alendronate (p <
.0001). Significantly greater BMD gains with denosumab compared with alendronate
also were achieved at 12 months at the lumbar spine, femoral neck, and 1/3 radius
(all p < .0125). Median serum CTX levels remained near baseline in the
alendronate group and were significantly decreased versus alendronate (p < .0001)
at all time points with denosumab. Adverse events and serious adverse events were
balanced between groups. No clinical hypocalcemic adverse events were reported.
Transition to denosumab produced greater increases in BMD at all measured
skeletal sites and a greater reduction in bone turnover than did continued
alendronate with a similar safety profile in both groups.
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