Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates
P D Miller1, N Pannacciulli1, J P Brown1
1Colorado Center for Bone Research (P.D.M.), Lakewood, Colorado 80277; Amgen Inc (N.P., C.W., R.B.W.), Thousand Oaks, California 91320; Laval University and Centre Hospitalier Universitaire de Québec Research Centre (J.P.B.), Québec City, Québec G1V 4G2, Canada; Krakow Medical Center (E.C.), 31-501 Krakow, Poland; Center for Clinical and Basic Research (B.S.N.), Aalborg, DK-9000 Aalborg, Denmark; Bethesda Health Research Center (M.A.B.), Bethesda, Maryland 20817; Hospital de la Santa Creu i Sant Pau (J.M.), 08025 Barcelona, Spain; Michigan Bone and Mineral Clinic (H.G.B.), Detroit, Michigan 48236; University of Liège (J.-Y.R.), 4000 Liège, Belgium; Georgetown University Medical Center (A.S.), Washington, DC 20007; and San Francisco Coordinating Center (S.R.C.), California Pacific Medical Center Research Institute, San Francisco, California 94143.
Context:
Denosumab and zoledronic acid (ZOL) are parenteral treatments for patients with osteoporosis.
Objective:
The objective of the study was to compare the effect of transitioning from oral bisphosphonates to denosumab or ZOL on bone mineral density (BMD) and bone turnover.
Design And Setting:
This was an international, multicenter, randomized, double-blind trial.
Participants:
A total of 643 postmenopausal women with osteoporosis previously treated with oral bisphosphonates participated in the study.
Interventions:
Subjects were randomized 1:1 to sc denosumab 60 mg every 6 months plus iv placebo once or ZOL 5 mg iv once plus sc placebo every 6 months for 12 months.
Main Outcome Measures:
Changes in BMD and bone turnover markers were measured.
Results:
BMD change from baseline at month 12 was significantly greater with denosumab compared with ZOL at the lumbar spine (primary end point; 3.2% vs 1.1%; P < .0001), total hip (1.9% vs 0.6%; P < .0001), femoral neck (1.2% vs -0.1%; P < .0001), and one-third radius (0.6% vs 0.0%; P < .05). The median decrease from baseline was greater with denosumab than ZOL for serum C-telopeptide of type 1 collagen at all time points after day 10 and for serum procollagen type 1 N-terminal propeptide at month 1 and at all time points after month 3 (all P < .05). Median percentage changes from baseline in serum intact PTH were significantly greater at months 3 and 9 with denosumab compared with ZOL (all P < .05). Adverse events were similar between groups. Three events consistent with the definition of atypical femoral fracture were observed (two denosumab and one ZOL).
Conclusions:
In postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab was associated with greater BMD increases at all measured skeletal sites and greater inhibition of bone remodeling compared with ZOL.
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