Randomized controlled trial of annual zoledronic acid to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer.
OBJECTIVE
Gonadotropin-releasing hormone (GnRH) agonists decrease bone mineral density (BMD) and increase fracture risk in men with prostate cancer. Annual zoledronic acid increases BMD in postmenopausal women, but its efficacy in hypogonadal men is not known.


METHODS
In a 12-month study, 40 men with nonmetastatic prostate cancer who were receiving a GnRH agonist and had T scores more than -2.5 were randomly assigned to zoledronic acid (4 mg intravenously on day 1 only) or placebo. BMD of the posteroanterior lumbar spine and proximal femur were measured by dual-energy x-ray absorptiometry.


RESULTS
Mean (+/- SE) BMD of the posteroanterior lumbar spine decreased by 3.1% +/- 1.0% in men assigned to placebo and increased by 4.0% +/- 1.0% in men assigned to zoledronic acid (P < .001). BMD of the total hip decreased by 1.9% +/- 0.7% in men assigned to placebo and increased by 0.7% +/- 0.5% in men assigned to zoledronic acid (P = .004). Similar between-group differences were observed for the femoral neck and trochanter. Serum N-telopeptide, a marker of osteoclast activity, decreased significantly after zoledronic acid treatment.


CONCLUSIONS
In men receiving a GnRH agonist, a single treatment with zoledronic acid significantly increased BMD and durably suppressed serum N-telopeptide levels for 12 months. Annual zoledronic acid may be a convenient and effective strategy to prevent bone loss in hypogonadal men.
Michaelson
M Dror
MD
Division of Hematology and Oncology and Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Kaufman
Donald S
DS
Lee
Hang
H
McGovern
Francis J
FJ
Kantoff
Philip W
PW
Fallon
Mary Anne
MA
Finkelstein
Joel S
JS
Smith
Matthew R
MR
D000368:Aged; D000726:Androgen Antagonists / Q000009:adverse effects*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016723:Bone Remodeling / Q000187:drug effects; D001900:Boston; D004164:Diphosphonates / Q000008:administration & dosage* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D050723:Fractures, Bone / Q000139:chemically induced / Q000517:prevention & control; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D000077211:Zoledronic Acid
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D007987:Gonadotropin-Releasing Hormone; D000077211:Zoledronic Acid