Session Information
Session Type: ACR Plenary Session
Session Time: 11:00AM-12:30PM
Background/Purpose: Oral bisphosphonates are the most common osteoporosis treatment,
but inconvenient dosing regimens and side effects lead to low adherence. Less frequently dosed bisphosphonates, eg, once yearly zoledronic
acid (ZOL), are part of the treatment algorithm for patients who have failed or
are intolerant to oral bisphosphonates. Yet
there is no evidence that cycling through bisphosphonates
offers therapeutic benefit. Denosumab (DMAb) has shown bone mineral
density (BMD) increases in subjects previously treated with oral bisphosphonates, in contrast to ZOL (McClung et
al. Bone 2007). This study evaluated DMAb
compared with ZOL in postmenopausal women with osteoporosis previously treated with oral bisphosphonates.
Methods: This
was a 12-month, multicenter, randomized, double-blind, double-dummy study in postmenopausal
women aged ≥ 55 years who had received oral bisphosphonates
for ≥ 2 years; had a BMD T-score ≤ –2.5 at the lumbar spine,
total hip, or femoral neck; and a serum C-telopeptide
of type 1 collagen (sCTX) ≤ 0.5 ng/mL. Subjects were randomized
1:1 to DMAb 60 mg every 6 months (Q6M) + placebo (intravenous [IV] once yearly)
or ZOL 5 mg IV once yearly + placebo (subcutaneous Q6M) for 12 months, and received
calcium and vitamin D daily. Endpoints included percentage
change from baseline in BMD at the lumbar
spine (primary endpoint), total hip, femoral neck,
and 1/3 radius at month 12. sCTX and procollagen type 1 N-terminal propeptide
(P1NP) were measured post baseline in a subset of subjects. Safety was also
assessed.
Results: A
total of 643 subjects were randomized (321 DMAb; 322
ZOL). Mean (SD) age was 69 (7) years, mean (SD) lumbar spine BMD T-score was –2.7
(0.8), and mean (SD) duration of prior oral bisphosphonates use was 6.3 (3.8)
years. BMD change from baseline at month 12 was significantly greater with DMAb
compared with ZOL at the lumbar spine (3.2% vs 1.1%; p < 0.0001;
Figure) and all other measured skeletal sites (Figure).
Median decrease from baseline was greater with DMAb compared with ZOL for
sCTX at months 1 (–78% vs –68%), 6 (–63% vs –22%),
and 12 (–63% vs 2%; all p < 0.01), and for P1NP at months 6
(–48% vs –30%) and 12 (–50% vs 4%; both p < 0.01). Overall and serious adverse events were similar
between groups. There were no cases of
osteonecrosis of the jaw, hypocalcemia, or delayed fracture healing. Three events consistent with the
definition of atypical femoral fracture were observed (2 DMAb; 1 ZOL).
Conclusion: In
postmenopausal women with osteoporosis previously
treated with oral bisphosphonates, DMAb treatment increased BMD at all measured skeletal
sites and reduced bone remodeling more than ZOL. No new safety risks were identified.
To cite this abstract in AMA style:
Miller P, Pannacciulli N, Brown J, Czerwinski E, Nedergaard B, Bolognese M, Malouf J, Bone H, Reginster J, Singer A, Wang C, Wagman R, Cummings S. A Randomized Double-Blind Study of Denosumab Compared with Zoledronic Acid in Postmenopausal Women with Osteoporosis Previously Treated with Oral Bisphosphonate [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/a-randomized-double-blind-study-of-denosumab-compared-with-zoledronic-acid-in-postmenopausal-women-with-osteoporosis-previously-treated-with-oral-bisphosphonate/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-randomized-double-blind-study-of-denosumab-compared-with-zoledronic-acid-in-postmenopausal-women-with-osteoporosis-previously-treated-with-oral-bisphosphonate/