Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates.
Denosumab and zoledronic acid (ZOL) are parenteral treatments for patients with osteoporosis.



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.



This was an international, multicenter, randomized, double-blind trial.



A total of 643 postmenopausal women with osteoporosis previously treated with oral bisphosphonates participated in the study.



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.



Changes in BMD and bone turnover markers were measured.



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).



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.
Colorado 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.
P D
PD
Miller
Colorado 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.
N
N
Pannacciulli
Colorado 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.
J P
JP
Brown
Colorado 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.
E
E
Czerwinski
Colorado 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.
B S
BS
Nedergaard
Colorado 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.
M A
MA
Bolognese
Colorado 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.
J
J
Malouf
Colorado 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.
H G
HG
Bone
Colorado 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.
J-Y
JY
Reginster
Colorado 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.
A
A
Singer
Colorado 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.
C
C
Wang
Colorado 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.
R B
RB
Wagman
Colorado 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.
S R
SR
Cummings
D000284:Administration, Oral; D000368:Aged; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D000069448:Denosumab / Q000627:therapeutic use*; D004164:Diphosphonates / Q000008:administration & dosage* / Q000627:therapeutic use; D004311:Double-Blind Method; D057915:Drug Substitution; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000069448:Denosumab; D000077211:Zoledronic Acid