In postmenopausal women with osteoporosis, 2 doses of zoledronate 5 mg at an approximately 6-year interval prevented bone loss for almost 11 years, according to study results published in The Journal of Clinical Endocrinology & Metabolism.
Although previous studies have shown that intravenous zoledronate therapy can prevent bone loss and reduce fracture risk in older adults, limited data are available on the long-term results of this treatment option and no studies have explored the effects of very infrequent doses of zoledronate beyond 5 years in postmenopausal women.
The goal of the current study was to explore the effects of dosing every 5.5 years with 5 mg of zoledronate on bone mineral density (BMD) and bone turnover markers in older postmenopausal women.
Of 50 women with osteopenia in the core trial who were randomly assigned to receive either a single 5-mg dose of zoledronate (mean age, 62 years) or placebo (mean age, 65 years), 33 entered a 5-year open-label extension study (17 from the placebo group and 16 from the intervention group). At an average of 5.5 years after initial study inclusion, all patients received a 5-mg dose of intravenous zoledronate. Follow-up continued for 5 years after the extension study zoledronate dose.
During the 11 total years of observation, BMD was higher in the group of patients who were treated with zoledronate in the core study followed by a second dose of zoledronate compared with patients who received placebo in the core study followed by a dose of zoledronate.
At approximately 11 years, BMD in the group that received 2 doses of zoledronate was at or above baseline levels at each site, with mean change from baseline of 3.8% at the spine (95% CI, 1.1-6.5), 0.9% at the total hip (95% CI , -1.7 to 3.5), and 0.4% at the total body 0.4% (95% CI, -0.8 to 1.6). The respective changes from baseline BMD in the group that received placebo followed by zoledronate were 2.9% (95% CI, 0.3-5.5), -2.8% (95% CI, -5.3 to -0.3), and -0.4% (95% CI, -1.3 to 0.5). The corresponding between-group differences for BMD changes were 0.8% (95% CI, -2.2 to 3.8; P =.61), 3.6% (95% CI, 1.1-6.2; P =.006) and 0.9% (95% CI, -0.3 to 2.0; P =.14), respectively.
In the group of patients who received zoledronate at both time points, the administration of the second dose of zoledronate produced only small effects on bone turnover markers compared with the values before the second dose. However, in the group of patients who received zoledronate after an initial dose of placebo, levels of β-C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) declined and were similar to those in the group of patients who received 2 zoledronate doses. For the duration of follow-up, the values in both groups remained similar.
There was no statistically significant difference in the occurrence of clinical fractures between the groups and there were no cases of atypical femoral fracture or osteonecrosis of the jaw.
The study’s small sample size and observational open-label design were noted as limitations.
“[T]his observational extension of a randomized trial suggests that 5.5-yearly dosing with 5mg of zoledronate prevents bone loss in older postmenopausal women for almost 11 years. Very infrequent treatment might be attractive to women wishing to preserve bone density into later life,” concluded the researchers.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Grey A, Horne A, Gamble G, Mihov B, Reid IR, Bolland M. Ten years of very infrequent zoledronate therapy in older women: an open-label extension of a randomized trial [published online February 4, 2020]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgaa062