Results of a 3-month randomized trial to examine week-by-week effects of monthly ibandronate on biochemical markers of bone resorption

Abstract

Aims: Bisphosphonates (BPs) bind preferentially to active bone remodeling sites where they decrease bone resorption through direct effects on osteoclasts. The number and depth of active bone resorption sites are considered important determinants of bone strength and fracture risk. Because resorption at a remodeling site is typically completed within 2–3 weeks, some resorption sites may proceed to completion if BPs are given at intervals greater than 1–2 weeks. We examined the pattern of urinary and serum resorption marker levels with monthly dosing of oral ibandronate, since no data are available on the effect of a monthly regimen on bone markers in the interval between doses. Methods: After a 4-week run-in of calcium and vitamin D, 203 postmenopausal osteoporotic women were randomized to receive 3 once-monthly doses of ibandronate 100 mg or 150 mg, or matching placebo. Patients and all study staff remained blinded to treatment allocation throughout the study. Serum CTx and urine NTx were measured at baseline (Week 0, just prior to first dose), one and 4 weeks after each dose and weekly after the third dose (Weeks 9–12). Geometric mean percent change from baseline was determined. Results: In each cycle, sCTx and uNTx decreases were less 4 weeks post-dose of ibandronate than at one week post-dose. Mean marker levels in ibandronate groups increased progressively throughout the 4 weeks following the third dose of ibandronate, but remained below placebo at all time points. Conclusions: Both sCTx and uNTx exhibited cyclic reductions with monthly dosing of oral ibandronate. The clinical implications of this effect are unknown and merit further investigation.