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