Changes in biochemical markers and bone mass after withdrawal of ibandronate treatment: prediction of bone mass changes during treatment.

The study was a 1 year randomized, double-blind, placebo-controlled study of ibandronate treatment in postmenopausal, osteopenic women. Participants were followed for 1 year after withdrawal of treatment. All women were at least 10 years past menopause and had a baseline bone mineral density (BMD) at the distal forearm at least 1.5 standard deviations below the premenopausal mean peak value. A total of 141 women (78%) completed the first year, and 119 women (66%) the second year of the study. The dose-response data of the first year have been published previously (Ravn et al. Bone 19:527-533;1996). In this study, we analyzed the biochemical markers as predictors of response in bone mass during ibandronate treatment, and report withdrawal data from the last year of the study, when ibandronate was discontinued. The relative change in the biochemical markers was significantly correlated to the response in BMD. At 12 months, the r values ranged from -0.29 to -0.47 (p < 0.01) and were highest for CrossLaps (uCL) and osteocalcin (OC(N-MID)). The quartiles of women with the most reduced concentrations of uCL and OC(N-MID) during treatment showed a 360-430% higher response in BMD compared to quartiles with less reduced concentrations (p < 0.01). During the withdrawal period, uCL and alkaline phosphatase (AP) returned to baseline values 12 months after discontinuation of treatment in all groups, whereas OC(N-MID) and bone-specific AP were still reduced 10%-25% in the groups previously treated with the highest doses of ibandronate (1.0-5.0 mg) (p < 0.01). In the withdrawal period, BMD decreased equally in all groups (analysis of variance; not significant); with a linear rate of 2%/year on average (p < 0.05 to < 0.001) at the spine and femur. In conclusion, uCL and OC(N-MID) can be used to predict the response in bone mass during ibandronate treatment. The bone loss that resumes after withdrawal of ibandronate treatment is of a magnitude similar to that of normal postmenopausal bone loss.