Intravenous zoledronic acid in postmenopausal women with low bone mineral density.
BACKGROUND
Bisphosphonates are effective agents for the management of osteoporosis. Their low bioavailability and low potency necessitate frequent administration on an empty stomach, which may reduce compliance. Gastrointestinal intolerance limits maximal dosing. Although intermittent intravenous treatments have been used, the optimal doses and dosing interval have not been systematically explored.


METHODS
We studied the effects of five regimens of zoledronic acid, the most potent bisphosphonate, on bone turnover and density in 351 postmenopausal women with low bone mineral density in a one-year, randomized, double-blind, placebo-controlled trial. Women received placebo or intravenous zoledronic acid in doses of 0.25 mg, 0.5 mg, or 1 mg at three-month intervals. In addition, one group received a total annual dose of 4 mg as a single dose, and another received two doses of 2 mg each, six months apart. Lumbar-spine bone mineral density was the primary end point.


RESULTS
There were similar increases in bone mineral density in all the zoledronic acid groups to values for the spine that were 4.3 to 5.1 percent higher than those in the placebo group (P<0.001) and values for the femoral neck that were 3.1 to 3.5 percent higher than those in the placebo group (P<0.001). Biochemical markers of bone resorption were significantly suppressed throughout the study in all zoledronic acid groups. Myalgia and pyrexia occurred more commonly in the zoledronic acid groups, but treatment-related dropout rates were similar to that in the placebo group.


CONCLUSIONS
Zoledronic acid infusions given at intervals of up to one year produce effects on bone turnover and bone density as great as those achieved with daily oral dosing with bisphosphonates with proven efficacy against fractures, suggesting that an annual infusion of zoledronic acid might be an effective treatment for postmenopausal osteoporosis.
Reid
Ian R
IR
Department of Medicine, University of Auckland, Auckland, New Zealand. i.reid@auckland.ac.nz
Brown
Jacques P
JP
Burckhardt
Peter
P
Horowitz
Zebulun
Z
Richardson
Peter
P
Trechsel
Ulrich
U
Widmer
Albert
A
Devogelaer
Jean-Pierre
JP
Kaufman
Jean-Marc
JM
Jaeger
Philippe
P
Body
Jean-Jacques
JJ
Brandi
Maria Luisa
ML
Broell
Johann
J
Di Micco
Raffaele
R
Genazzani
Andrea Riccardo
AR
Felsenberg
Dieter
D
Happ
Joachim
J
Hooper
Michael J
MJ
Ittner
Jochen
J
Leb
Georg
G
Mallmin
Hans
H
Murray
Timothy
T
Ortolani
Sergio
S
Rubinacci
Alessandro
A
Saaf
Maria
M
Samsioe
Goran
G
Verbruggen
Leon
L
Meunier
Pierre J
PJ
D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D003094:Collagen / Q000097:blood / Q000652:urine; D024042:Collagen Type I; D003404:Creatinine / Q000652:urine; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D007262:Infusions, Intravenous; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000503:physiopathology; D010455:Peptides / Q000097:blood / Q000652:urine; D000077211:Zoledronic Acid
D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000077211:Zoledronic Acid; D003094:Collagen; D003404:Creatinine