Zoledronic acid and clinical fractures and mortality after hip fracture.
Mortality is increased after a hip fracture, and strategies that improve outcomes are needed.



In this randomized, double-blind, placebo-controlled trial, 1065 patients were assigned to receive yearly intravenous zoledronic acid (at a dose of 5 mg), and 1062 patients were assigned to receive placebo. The infusions were first administered within 90 days after surgical repair of a hip fracture. All patients (mean age, 74.5 years) received supplemental vitamin D and calcium. The median follow-up was 1.9 years. The primary end point was a new clinical fracture.



The rates of any new clinical fracture were 8.6% in the zoledronic acid group and 13.9% in the placebo group, a 35% risk reduction with zoledronic acid (P=0.001); the respective rates of a new clinical vertebral fracture were 1.7% and 3.8% (P=0.02), and the respective rates of new nonvertebral fractures were 7.6% and 10.7% (P=0.03). In the safety analysis, 101 of 1054 patients in the zoledronic acid group (9.6%) and 141 of 1057 patients in the placebo group (13.3%) died, a reduction of 28% in deaths from any cause in the zoledronic acid group (P=0.01). The most frequent adverse events in patients receiving zoledronic acid were pyrexia, myalgia, and bone and musculoskeletal pain. No cases of osteonecrosis of the jaw were reported, and no adverse effects on the healing of fractures were noted. The rates of renal and cardiovascular adverse events, including atrial fibrillation and stroke, were similar in the two groups.



An annual infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture was associated with a reduction in the rate of new clinical fractures and with improved survival. (ClinicalTrials.gov number, NCT00046254 [ClinicalTrials.gov].).
Lyles
Kenneth W
KW
Duke University Medical Center, Durham, NC, USA.
Colón-Emeric
Cathleen S
CS
Magaziner
Jay S
JS
Adachi
Jonathan D
JD
Pieper
Carl F
CF
Mautalen
Carlos
C
Hyldstrup
Lars
L
Recknor
Chris
C
Nordsletten
Lars
L
Moore
Kathy A
KA
Lavecchia
Catherine
C
Zhang
Jie
J
Mesenbrink
Peter
P
Hodgson
Patricia K
PK
Abrams
Ken
K
Orloff
John J
JJ
Horowitz
Zebulun
Z
Eriksen
Erik Fink
EF
Boonen
Steven
S
D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002118:Calcium / Q000627:therapeutic use; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology / Q000517:prevention & control*; D006620:Hip Fractures / Q000188:drug therapy / Q000401:mortality* / Q000601:surgery; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D014807:Vitamin D / Q000627:therapeutic use; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D014807:Vitamin D; D000077211:Zoledronic Acid; D002118:Calcium