Extended Treatment Effects
with Zoledronic Acid
Based on Poster 1070
“The Effect of 3 Versus 6 Years of Zoledronic Acid Treatment in Osteoporosis:
a Randomized Extension to the HORIZON-Pivotal Fracture Trial (PFT)”
Saturday, October 16, 2010
ASBMR 2010
Toronto, Ontario
Background and Method
• Zoledronic acid (ZA) 5 mg used annually for 3 years has been shown to be
effective in increasing BMD and decreasing fractures
• The extension trial of HORIZON-PFT evaluated the effect of continuing ZA
for 3 more years
• All patients eligible for the extension trial had to have received all 3 annual
infusions of ZA
• A total of 1233 women were randomized to either ZA for 3 more years
(Z6 group) or to placebo (Z3P3 group)
• Baseline characteristics of the two groups were similar with about half of each
group having bone mineral density (BMD) T-scores at the femoral neck <-2.5
and about 60% having 1 or more vertebral fractures.
End Points
Primary Outcome Measure:
Per cent change in BMD of femoral neck at year 6 relative to year 3
Secondary Outcome Measures:
• Change from baseline of biochemical markers of bone turnover
at different time points
• Per cent change from baseline in BMD of spine and distal radius at
year 4.5 and 6
• Per cent change from baseline in BMD of femoral neck, total hip and trochanter
at different time points
• Proportion of patients with new vertebral fractures and incidence of
clinical fracture
• Bone biopsy to evaluate bone quality
• Evaluation of safety parameters (renal function, laboratory parameters,
adverse event profile)
Results
Mean per cent change in femoral neck BMD over the 3-year extension remained
constant in the Z6 group compared with a slight drop in the Z3P3 group for a
between-group difference at year 6 of 1.04% (P=0.0009)
Results
• Mean per cent changes in total hip BMD were similar to those at the femoral
neck at 4.2% for the Z6 group vs. 2.8% for the Z3P3 group
• Over the 6 years of treatment, the Z6 group had a significant mean femoral
neck BMD increase of 4.5% vs. 3.1% for the Z3P3 group
• Mean lumbar spine BMD increased by 12% from baseline for the Z6 group vs.
10% from baseline in the Z3P3 which was not statistically significant
• Biochemical markers remained constant in the Z6 group but rose slightly in the
Z3P3 group
Results
• The morphometric verterbral fracture rate was 6.2% in the Z3P3 group;
this rate was reduced by about 52% in the group receiving ZA for 6 years
• Only 11 clinical vertebral fractures were seen during the extension study and
there was no difference between the 2 groups
• There was no difference in non-vertebral fracture rates between the 2 groups
• A total of 15 hip fractures occurred during the extension study and there was
no difference in hip fracture rates between the 2 groups
Adverse Events (AEs)
• Overall AEs were similar in the 2 groups; serious AEs were numerically more
frequent in the Z6 group but this difference was not statistically significant
• No long-term effect on renal function was observed and there were no
differences in CV event rates between the 2 groups
• Only 1 case of osteonecrosis of the jaw occurred in the Z6 group and there
were no atypical fractures in either group
• Hypertension was almost twice as common in the Z3P3 group vs. the Z6 group
Conclusions
• A comparable safety profile was observed in the 3-year extension with the first
3-year data
• After 3 years of ZA therapy, it may be beneficial for some women, particularly
those at high risk for vertebral fracture, to continue on ZA
• In making decisions about long-term use of BPs, it is important to
individualize treatment decisions and to try to identify women for whom a drug
holiday may be appropriate