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.