Effect of oral zoledronate administration on bone turnover in older women

摘要

Aim: The aim of this work is to assess the safety and efficacy of two oral zoledronate preparations by determining their effects on bone resorption in healthy postmenopausal women. Methods: The preparations studied were zoledronic acid in enteric-coated capsules or a microparticle preparation of zoledronic acid in these capsules. Bone resorption was measured as beta-C-telopeptideof type I collagen (CTX) in fasting serum. Separate cohorts, each of five women, were recruited and allocated in sequence to single doses of 20 mg, 40 mg, or 60 mg of oral zoledronate. Results: Zoledronate 20 mg enteric capsules were well tolerated, reduced serum CTX by a median 51 at 1 week, but by only 17 at 1 month. Doses of 40 or 60 mg of this preparation produced APR and/or gastrointestinal symptoms in more than half of participants. With these doses, median CTX reduction at 1 week was >80, similar to 70 at 1 month, but only similar to 30 at 6 months. Enteric capsules containing microparticles of zoledronate 20 mg reduced CTX by a median 53 at 1 week, with offset over 3 months. Two or three of these capsules dosed weekly reduced CTX by similar to 50 at 1 month, and by similar to 30 at 3 and 6 months. Conclusions: Oral zoledronate 20 mg circumvents the problem of APR symptoms but, even with multiple doses, the anti-resorptive effect is smaller and less sustained than with intravenous zoledronate. Probably a viable oral regimen of zoledronate dosing at intervals of weeks to months could be developed, but the advantage of infrequent dosing would be lost.