Oral ibandronate: changes in markers of bone turnover during adequately dosed continuous and weekly therapy and during different suboptimally dosed treatment regimens

The aims of the present study were to investigate how changes in the cumulative dose and the frequency of dosing influence the short-term antiresorptive efficacy of oral ibandronate treatment and whether serial measurements of bone markers could provide a useful diagnostic tool for the revelation of noncompliance to established treatments with antiresorptive drugs. Study participants were 200 healthy women 50–70 years old (mean 63.1 years) with a lumbar spine BMD t-score of −1 to −5. Women were randomly allocated to receive treatment with oral ibandronate according to one of the following eight dosing regimes: (1) 2.5 mg daily for 84 days; (2) 20 mg weekly for 84 days; (3) 2.5 mg daily for 28 days + no treatment for 56 days; (4) 2.5 mg daily for 28 days + 2.5 mg weekly for 56 days; (5) 2.5 mg daily for 28 days + 2.5 mg three times weekly for 56 days; (6) 2.5 mg daily for 14 days + 2.5 mg three times weekly for 56 days; (7) 2.5 mg three times weekly for 84 days; (8) no treatment for 168 days. Study parameters were the serum concentration of the C-terminal telopeptide of collagen type I (s-CTX, resorption marker) and N-MID osteocalcin (formation marker) measured by enzyme-linked immunosorbent assay. Oral treatment with ibandronate 20 mg weekly (cumulative dose 240 mg) resulted in greater final inhibition in s-CTX and area under the curve (AUC) compared to the 2.5 mg daily treatment (cumulative dose 210 mg), indicating that as long as optimal doses are administered the frequency of dosing has secondary importance for overall efficacy. When the cumulative dose was 130 mg or less, the final degree of inhibition was still the function of the cumulative dose, but the overall efficacy estimated by the AUC was also under the influence of the frequency of dosing. These observations suggest that serial measurements of s-CTX may provide a useful diagnostic tool for the early revelation of suboptimal dosing or noncompliance to already optimized therapies with antiresorptive agents.