Prevention of bone loss by zoledronic acid in premenopausal women undergoing adjuvant chemotherapy persist up to one year following discontinuing treatment.
BACKGROUND
Adjuvant chemotherapy is associated with significant reductions in bone mineral density (BMD) in premenopausal women with breast cancer (BC) that is prevented with zoledronic acid (ZA) every 3 months for 1 yr.


OBJECTIVE
The aim of the study was to examine the effect on BMD of discontinuing ZA during the subsequent year.


METHODS
We conducted a randomized, double-blind trial.


METHODS
Premenopausal women (mean age, 42 yr) undergoing adjuvant chemotherapy for BC participated in the study.


METHODS
ZA (4 mg iv every 3 months) vs. placebo was administered for 12 months.


METHODS
We measured percentage change in BMD and bone turnover markers at 12 and 24 months (1 yr after last infusion).


RESULTS
Of 101 women randomized, 85 completed 12-month and 62 completed 24-month evaluations. In the placebo group, serum C-telopeptide (CTX) increased progressively over the first 12 months, returned toward baseline but remained significantly above baseline by 24 months. Lumbar spine BMD decreased from baseline by 5.5% at 12 and 6.3% at 24 months. Similarly, by 24 months, total hip and femoral neck BMD declined by 2.6 and 2.4%, respectively. In ZA patients, BMD remained stable (P < 0.0001 compared to placebo). Serum CTX declined significantly by 6 months, but returned to baseline by 12 months, remaining there at 24 months.


CONCLUSIONS
Premenopausal women receiving chemotherapy for BC sustained significant bone loss during the first year, without recovery during the second year. ZA effectively prevented bone loss during the first year of chemotherapy. BMD remained stable 1 yr after completion of ZA. Serum CTX increased significantly by 12 and 24 months. More frequent administration may be required to suppress bone resorption in this patient population.
Hershman
Dawn L
DL
M.S., Columbia University, 161 Fort Washington Avenue, 10-1068, New York, New York 10032, USA. dlh23@columbia.edu
McMahon
Donald J
DJ
Crew
Katherine D
KD
Shao
Theresa
T
Cremers
Serge
S
Brafman
Lois
L
Awad
Danielle
D
Shane
Elizabeth
E
D000328:Adult; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016723:Bone Remodeling; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D004164:Diphosphonates / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008875:Middle Aged; D010024:Osteoporosis / Q000517:prevention & control*; D017697:Premenopause; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid