Ten Years of Very Infrequent Zoledronate Therapy in Older Women: An Open-Label Extension of a Randomized Trial.

CONTEXT

Intravenous zoledronate prevents bone loss and reduces fracture risk in older adults but the optimal dosing strategy required to achieve each outcome is not known.

OBJECTIVE

To assess the effect of very infrequent zoledronate therapy on bone mineral density (BMD) and markers of bone turnover.

DESIGN AND PARTICIPANTS

An average of 5.5 years after randomization to either a single dose of 5 mg of zoledronateor placebo, 33 of the original cohort of 50 older women with osteopenia entered a 5-year open-label extension study.

SETTING

Academic research center.

INTERVENTION

A 5-mg dose of intravenous zoledronate was administered to all participants.

MAIN OUTCOME MEASURES

BMD and bone turnover were measured annually, generating data over almost 11 years in women who received 5 mg of zoledronate at 0 and 5.5 years (ZZ, n = 16), or placebo at baseline and 5 mg of zoledronate at 5.5 years (PZ, n = 17).

RESULTS

After redosing, BMD in ZZ remained stable, while BMD in PZ increased. At 11 years, changes from baseline BMD in ZZ and PZ were 3.8% (95% confidence interval (CI) 1.1,6.5) and 2.9% (0.3,5.5) at the lumbar spine (P = .61), 0.9% (-1.7,3.5) and -2.8% (-5.3,-0.3) at the total hip (P = .006), and 0.4% (-0.8,1.6) and -0.4% (-1.3,0.5) at the total body (P = .14). Bone turnover markers were similar in the PZ and ZZ groups throughout the 5 years after redosing.

CONCLUSIONS

These results suggest that zoledronate 5 mg administered at a 5.5-year interval prevents bone loss over almost 11 years. Clinical trials to investigate whether very infrequent treatment with zoledronate reduces fracture risk are justified.