Ibandronate: a comparison of oral daily dosing versus intermittent dosing in postmenopausal osteoporosis.
The objective of this study was to compare efficacy and safety of continuous versus intermittent oral dosing of ibandronate. Two hundred forty women aged 55-75 years with postmenopausal osteoporosis were randomized to active treatment or placebo. Similar total doses of ibandronate were provided by treatment regimens with either continuous 2.5 mg of ibandronate daily (n = 81) or intermittent 20 mg of ibandronate every other day for the first 24 days, followed by 9 weeks without active drug (n = 78). The placebo group (total, n = 81) was crossed over after 12 months to receive either continuous (n = 37) or intermittent ibandronate (n = 35). By 24 months, bone mineral density (BMD) had increased significantly relative to baseline in both active treatment groups. The continuous and intermittent groups showed statistically equivalent increases in lumbar spine BMD of +5.64% (+/-0.53) and +5.54% (+/-0.53) and in total hip of +3.35% (+/-0.40) and +3.41% (+/-0.40), respectively (per protocol population). Biochemical markers of bone turnover decreased significantly in both treatment groups. The level of marker suppression was similar, although the intermittent group displayed, as expected, more fluctuation over the treatment period. The frequency of adverse events was similar in the treatment groups. In conclusion, the intermittent and continuous regimens showed equivalent changes in BMD and bone turnover. These results confirm previous preclinical findings indicating that the efficacy of ibandronate depends on the total oral dose given rather than on the dosing schedule. This supports development of new flexible dosing regimens targeted to minimize the frequency of dosing, which are expected to improve convenience and lead to enhanced long-term patient compliance.
Riis
B J
BJ
Center for Clinical and Basic Research, Ballerup, Denmark.
Ise
J
J
von Stein
T
T
Bagger
Y
Y
Christiansen
C
C
D000284:Administration, Oral; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption; D003257:Consumer Product Safety; D018592:Cross-Over Studies; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005260:Female; D006615:Hip / Q000503:physiopathology; D006801:Humans; D000077557:Ibandronic Acid; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000503:physiopathology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine
D015415:Biomarkers; D004164:Diphosphonates; D000077557:Ibandronic Acid