Zoledronic acid inhibits adjuvant letrozole-induced bone loss in postmenopausal women with early breast cancer.
OBJECTIVE
Treatment with aromatase inhibitors decreases bone mineral density (BMD) and may increase the risk of fractures in postmenopausal women with early-stage breast cancer. The addition of zoledronic acid to adjuvant letrozole therapy may protect against bone loss.


METHODS
Patients receiving adjuvant letrozole were randomly assigned to receive either upfront or delayed-start zoledronic acid (4 mg intravenously every 6 months). The delayed group received zoledronic acid when lumbar spine (LS) or total hip (TH) T score decreased to less than -2.0 or when a nontraumatic fracture occurred. The primary end point of this study was to compare the change in LS BMD at month 12 between the groups. Secondary end points included change in TH BMD and changes in serum bone turnover markers at month 12.


RESULTS
The upfront and delayed groups each included 301 patients. At month 12, LS BMD was 4.4% higher in the upfront group than in the delayed group (95% CI, 3.7% to 5.0%; P < .0001), and TH BMD was 3.3% higher (95% CI, 2.8% to 3.8%; P < .0001). In the upfront group, mean serum N-telopeptide and bone-specific alkaline phosphatase concentrations decreased by 15.1% (P < .0001) and 8.8% (P = .0006), respectively, at month 12, whereas concentrations increased significantly in the delayed group by 19.9% (P = .013) and 24.3% (P < .0001), respectively.


CONCLUSIONS
With 1 year of follow-up, results of the primary end point of the Zometa-Femara Adjuvant Synergy Trial (Z-FAST) indicate that upfront zoledronic acid therapy prevents bone loss in the LS in postmenopausal women receiving adjuvant letrozole for early-stage breast cancer.
Brufsky
Adam
A
Magee-Womens Hospital, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15123, USA. brufskyam@upmc.edu
Harker
W Graydon
WG
Beck
J Thaddeus
JT
Carroll
Robert
R
Tan-Chiu
Elizabeth
E
Seidler
Christopher
C
Hohneker
John
J
Lacerna
Leo
L
Petrone
Stephanie
S
Perez
Edith A
EA
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D024042:Collagen Type I / Q000097:blood; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects*; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D010455:Peptides / Q000097:blood; D014230:Triazoles / Q000009:adverse effects*; D000077211:Zoledronic Acid
D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D009570:Nitriles; D010455:Peptides; D014230:Triazoles; C052929:collagen type I trimeric cross-linked peptide; D000077211:Zoledronic Acid; D000077289:Letrozole; D000469:Alkaline Phosphatase