The HORIZON Recurrent Fracture Trial: design of a clinical trial in the prevention of subsequent fractures after low trauma hip fracture repair.
OBJECTIVE
To present the novel design of a trial testing the safety and efficacy of a yearly bisphosponate, zoledronic acid, in preventing new clinical fractures in patients with recent low trauma hip fracture repair.


METHODS
Randomized, placebo-controlled, triple-blind study. One hundred and fifteen clinical centers worldwide are recruiting approximately 1714 subjects aged 50 years and over (no upper age limit, median age of enrolled subjects to date 79 years) who have undergone surgical repair of a low trauma hip fracture in the preceding 90 days. Patients will be assigned at random to an intervention group (5 mg zoledronic acid intravenously yearly) or a control group (placebo infusion yearly). Both groups receive a loading dose of Vitamin D2 or D3 IM or orally, followed by 800-1200 IU Vitamin D and 1000-1500 mg elemental calcium orally on a daily basis. Concomitant therapy with calcitonin, hormone replacement therapy, selective estrogen receptor modulators, tibolone, and external hip protectors are allowed.


METHODS
The primary endpoint is subsequent skeletal fractures as adjudicated by a clinical endpoints committee blinded to intervention status. Secondary outcomes include delayed hip fracture healing, changes in bone mineral density, and health resource utilization. Subjects will be recruited over a 3-4 year period and will be followed until 211 primary endpoints are accrued and adjudicated.


CONCLUSIONS
This randomized clinical trial is novel among osteoporosis therapies as it (1). targets hip fracture patients, a previously understudied group, and (2). uses only clinically evident fractures as the primary outcome. Ethical and practical considerations in studying this frail population are discussed.
Colón-Emeric
Cathleen S
CS
Center for the Study of Aging and Human Development, Box 3003, Duke University Medical Center, Durham, NC 27710, USA. colon001@mc.duke.edu
Caminis
John
J
Suh
Theodore T
TT
Pieper
Carl F
CF
Janning
Cheri
C
Magaziner
Jay
J
Adachi
Jonathan
J
Rosario-Jansen
Theresa
T
Mesenbrink
Peter
P
Horowitz
Zeb D
ZD
Lyles
Kenneth W
KW
D015519:Bone Density; D002118:Calcium / Q000008:administration & dosage; D019049:Developed Countries; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006620:Hip Fractures / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D014807:Vitamin D / Q000008:administration & dosage; D000077211:Zoledronic Acid
D004164:Diphosphonates; D007093:Imidazoles; D010919:Placebos; D014807:Vitamin D; D000077211:Zoledronic Acid; D002118:Calcium